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Epidemiology of NAFLD in China
Jian-Gao Fan MD PhD
Professor and DirectorDepartment of Gastroenterology
Xinhua Hospital Shanghai Jiaotong University School of Medicine
Shanghai 200092 China
Epidemiological studies in FLD
◼ Case definition
Liver biopsy
CT scan
Ultrasound
FibroScanFibroTouch
FLI HSI
◼ Sampling frame
Population
Community
Clinical based
Hospital based
--ConsecutiveNon-consecutive
Ultrasound of fatty liver
Fatty liver in given specific Chinese population
◼ Labor workers in Daqing Liaonin (n=4100) 5
◼ Labor workers in Beijing (n=1050) 11
◼ Employees in Shaoxing Zhejiang (n=11372) 10
◼ White collars in Beijing (n=818) 18
◼ White collars in Shanghai (n=4009) 13
◼ Among 6553 employees in Lianyungang Jiangsu
retired cadre 10 policemen 9 clerk 6
workmen 4
Fan JG Review Shijie Huaren Xiaohua Zazhi 200196-10
Increased prevalence of fatty liver in China
City Period Subjects Trend
Beijing 1998-2003 Administrative
officers
23 to 26
Shanghai 1995-2002 Factory
workers
4 to 14
Wuhan 1995-2004 Office workers 125 to 245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Consensus of management of FLD by
Chinese Society of Medicine
① Guideline for the diagnosis of
NAFLD and ALD
Chin J Hepatol 2001 amp 2003
② Guidelines for diagnosis and
treatment of NAFLD amp ALD
J Dig Dis 2008 9108-116
③ Chinese Guidelines for
diagnosis and management of
NAFLD amp ALD update 2010
J Dig Dis 2011 12 38-50
40
Definition of NAFLD
◼ There is evidence of hepatic steatosis either by
imaging or by histology and no causes for
secondary steatosis
NAFLD is a highly prevalent form of FLD
caused by over-nutrition
NAFLD is an acquired metabolic stress-
induced liver diseases associated with insulin
resistance and genetic susceptibility
Fatty liver in general population in China
CityYear Prevalence Etiology Others
Shanghai2005 173 AFL 08 NAFL 15
Other 12
Drinking 13
Guangzhou2007 145 AFL 05 NAFL 117
Other 18
Children 13
Xirsquoan2008 136 AFL 87 () NAFL 147 Drinking 66
Chengdu2009 125 AFL 26 NAFL 63
Other 36
Beijing2013 351 AFL 41 NAFL 313
Shanghai2014 37218810(40-70 yrs in
Chongming Island)
NAFLD 422 276 in NGT 457 in
pre-diabetes 625 in
diabetes persons
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87
Li HBPD Int 20098377-82Yan JGH 2013 281654-9 Yang Z Sci Rep 2016637886
Prevalence of Fatty Liver in Shanghai Adults
◼ Total 17◼ Male 19
◼ Female 15
◼ NAFLD 15
◼ AFL 08
◼ Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
57
NAFLD 88
AFLMixed FL
Criteria for obesity and MetS
ethnic differences
◼ Only 2-3 of Asians classified as obesity by Western criteria
◼ All Asian populations studied had a higher BF at a lower BMI compared to Caucasians
◼ For the same BF their BMI was 3-5 units lower compared to Caucasians
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Epidemiological studies in FLD
◼ Case definition
Liver biopsy
CT scan
Ultrasound
FibroScanFibroTouch
FLI HSI
◼ Sampling frame
Population
Community
Clinical based
Hospital based
--ConsecutiveNon-consecutive
Ultrasound of fatty liver
Fatty liver in given specific Chinese population
◼ Labor workers in Daqing Liaonin (n=4100) 5
◼ Labor workers in Beijing (n=1050) 11
◼ Employees in Shaoxing Zhejiang (n=11372) 10
◼ White collars in Beijing (n=818) 18
◼ White collars in Shanghai (n=4009) 13
◼ Among 6553 employees in Lianyungang Jiangsu
retired cadre 10 policemen 9 clerk 6
workmen 4
Fan JG Review Shijie Huaren Xiaohua Zazhi 200196-10
Increased prevalence of fatty liver in China
City Period Subjects Trend
Beijing 1998-2003 Administrative
officers
23 to 26
Shanghai 1995-2002 Factory
workers
4 to 14
Wuhan 1995-2004 Office workers 125 to 245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Consensus of management of FLD by
Chinese Society of Medicine
① Guideline for the diagnosis of
NAFLD and ALD
Chin J Hepatol 2001 amp 2003
② Guidelines for diagnosis and
treatment of NAFLD amp ALD
J Dig Dis 2008 9108-116
③ Chinese Guidelines for
diagnosis and management of
NAFLD amp ALD update 2010
J Dig Dis 2011 12 38-50
40
Definition of NAFLD
◼ There is evidence of hepatic steatosis either by
imaging or by histology and no causes for
secondary steatosis
NAFLD is a highly prevalent form of FLD
caused by over-nutrition
NAFLD is an acquired metabolic stress-
induced liver diseases associated with insulin
resistance and genetic susceptibility
Fatty liver in general population in China
CityYear Prevalence Etiology Others
Shanghai2005 173 AFL 08 NAFL 15
Other 12
Drinking 13
Guangzhou2007 145 AFL 05 NAFL 117
Other 18
Children 13
Xirsquoan2008 136 AFL 87 () NAFL 147 Drinking 66
Chengdu2009 125 AFL 26 NAFL 63
Other 36
Beijing2013 351 AFL 41 NAFL 313
Shanghai2014 37218810(40-70 yrs in
Chongming Island)
NAFLD 422 276 in NGT 457 in
pre-diabetes 625 in
diabetes persons
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87
Li HBPD Int 20098377-82Yan JGH 2013 281654-9 Yang Z Sci Rep 2016637886
Prevalence of Fatty Liver in Shanghai Adults
◼ Total 17◼ Male 19
◼ Female 15
◼ NAFLD 15
◼ AFL 08
◼ Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
57
NAFLD 88
AFLMixed FL
Criteria for obesity and MetS
ethnic differences
◼ Only 2-3 of Asians classified as obesity by Western criteria
◼ All Asian populations studied had a higher BF at a lower BMI compared to Caucasians
◼ For the same BF their BMI was 3-5 units lower compared to Caucasians
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Ultrasound of fatty liver
Fatty liver in given specific Chinese population
◼ Labor workers in Daqing Liaonin (n=4100) 5
◼ Labor workers in Beijing (n=1050) 11
◼ Employees in Shaoxing Zhejiang (n=11372) 10
◼ White collars in Beijing (n=818) 18
◼ White collars in Shanghai (n=4009) 13
◼ Among 6553 employees in Lianyungang Jiangsu
retired cadre 10 policemen 9 clerk 6
workmen 4
Fan JG Review Shijie Huaren Xiaohua Zazhi 200196-10
Increased prevalence of fatty liver in China
City Period Subjects Trend
Beijing 1998-2003 Administrative
officers
23 to 26
Shanghai 1995-2002 Factory
workers
4 to 14
Wuhan 1995-2004 Office workers 125 to 245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Consensus of management of FLD by
Chinese Society of Medicine
① Guideline for the diagnosis of
NAFLD and ALD
Chin J Hepatol 2001 amp 2003
② Guidelines for diagnosis and
treatment of NAFLD amp ALD
J Dig Dis 2008 9108-116
③ Chinese Guidelines for
diagnosis and management of
NAFLD amp ALD update 2010
J Dig Dis 2011 12 38-50
40
Definition of NAFLD
◼ There is evidence of hepatic steatosis either by
imaging or by histology and no causes for
secondary steatosis
NAFLD is a highly prevalent form of FLD
caused by over-nutrition
NAFLD is an acquired metabolic stress-
induced liver diseases associated with insulin
resistance and genetic susceptibility
Fatty liver in general population in China
CityYear Prevalence Etiology Others
Shanghai2005 173 AFL 08 NAFL 15
Other 12
Drinking 13
Guangzhou2007 145 AFL 05 NAFL 117
Other 18
Children 13
Xirsquoan2008 136 AFL 87 () NAFL 147 Drinking 66
Chengdu2009 125 AFL 26 NAFL 63
Other 36
Beijing2013 351 AFL 41 NAFL 313
Shanghai2014 37218810(40-70 yrs in
Chongming Island)
NAFLD 422 276 in NGT 457 in
pre-diabetes 625 in
diabetes persons
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87
Li HBPD Int 20098377-82Yan JGH 2013 281654-9 Yang Z Sci Rep 2016637886
Prevalence of Fatty Liver in Shanghai Adults
◼ Total 17◼ Male 19
◼ Female 15
◼ NAFLD 15
◼ AFL 08
◼ Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
57
NAFLD 88
AFLMixed FL
Criteria for obesity and MetS
ethnic differences
◼ Only 2-3 of Asians classified as obesity by Western criteria
◼ All Asian populations studied had a higher BF at a lower BMI compared to Caucasians
◼ For the same BF their BMI was 3-5 units lower compared to Caucasians
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Fatty liver in given specific Chinese population
◼ Labor workers in Daqing Liaonin (n=4100) 5
◼ Labor workers in Beijing (n=1050) 11
◼ Employees in Shaoxing Zhejiang (n=11372) 10
◼ White collars in Beijing (n=818) 18
◼ White collars in Shanghai (n=4009) 13
◼ Among 6553 employees in Lianyungang Jiangsu
retired cadre 10 policemen 9 clerk 6
workmen 4
Fan JG Review Shijie Huaren Xiaohua Zazhi 200196-10
Increased prevalence of fatty liver in China
City Period Subjects Trend
Beijing 1998-2003 Administrative
officers
23 to 26
Shanghai 1995-2002 Factory
workers
4 to 14
Wuhan 1995-2004 Office workers 125 to 245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Consensus of management of FLD by
Chinese Society of Medicine
① Guideline for the diagnosis of
NAFLD and ALD
Chin J Hepatol 2001 amp 2003
② Guidelines for diagnosis and
treatment of NAFLD amp ALD
J Dig Dis 2008 9108-116
③ Chinese Guidelines for
diagnosis and management of
NAFLD amp ALD update 2010
J Dig Dis 2011 12 38-50
40
Definition of NAFLD
◼ There is evidence of hepatic steatosis either by
imaging or by histology and no causes for
secondary steatosis
NAFLD is a highly prevalent form of FLD
caused by over-nutrition
NAFLD is an acquired metabolic stress-
induced liver diseases associated with insulin
resistance and genetic susceptibility
Fatty liver in general population in China
CityYear Prevalence Etiology Others
Shanghai2005 173 AFL 08 NAFL 15
Other 12
Drinking 13
Guangzhou2007 145 AFL 05 NAFL 117
Other 18
Children 13
Xirsquoan2008 136 AFL 87 () NAFL 147 Drinking 66
Chengdu2009 125 AFL 26 NAFL 63
Other 36
Beijing2013 351 AFL 41 NAFL 313
Shanghai2014 37218810(40-70 yrs in
Chongming Island)
NAFLD 422 276 in NGT 457 in
pre-diabetes 625 in
diabetes persons
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87
Li HBPD Int 20098377-82Yan JGH 2013 281654-9 Yang Z Sci Rep 2016637886
Prevalence of Fatty Liver in Shanghai Adults
◼ Total 17◼ Male 19
◼ Female 15
◼ NAFLD 15
◼ AFL 08
◼ Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
57
NAFLD 88
AFLMixed FL
Criteria for obesity and MetS
ethnic differences
◼ Only 2-3 of Asians classified as obesity by Western criteria
◼ All Asian populations studied had a higher BF at a lower BMI compared to Caucasians
◼ For the same BF their BMI was 3-5 units lower compared to Caucasians
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Increased prevalence of fatty liver in China
City Period Subjects Trend
Beijing 1998-2003 Administrative
officers
23 to 26
Shanghai 1995-2002 Factory
workers
4 to 14
Wuhan 1995-2004 Office workers 125 to 245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Consensus of management of FLD by
Chinese Society of Medicine
① Guideline for the diagnosis of
NAFLD and ALD
Chin J Hepatol 2001 amp 2003
② Guidelines for diagnosis and
treatment of NAFLD amp ALD
J Dig Dis 2008 9108-116
③ Chinese Guidelines for
diagnosis and management of
NAFLD amp ALD update 2010
J Dig Dis 2011 12 38-50
40
Definition of NAFLD
◼ There is evidence of hepatic steatosis either by
imaging or by histology and no causes for
secondary steatosis
NAFLD is a highly prevalent form of FLD
caused by over-nutrition
NAFLD is an acquired metabolic stress-
induced liver diseases associated with insulin
resistance and genetic susceptibility
Fatty liver in general population in China
CityYear Prevalence Etiology Others
Shanghai2005 173 AFL 08 NAFL 15
Other 12
Drinking 13
Guangzhou2007 145 AFL 05 NAFL 117
Other 18
Children 13
Xirsquoan2008 136 AFL 87 () NAFL 147 Drinking 66
Chengdu2009 125 AFL 26 NAFL 63
Other 36
Beijing2013 351 AFL 41 NAFL 313
Shanghai2014 37218810(40-70 yrs in
Chongming Island)
NAFLD 422 276 in NGT 457 in
pre-diabetes 625 in
diabetes persons
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87
Li HBPD Int 20098377-82Yan JGH 2013 281654-9 Yang Z Sci Rep 2016637886
Prevalence of Fatty Liver in Shanghai Adults
◼ Total 17◼ Male 19
◼ Female 15
◼ NAFLD 15
◼ AFL 08
◼ Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
57
NAFLD 88
AFLMixed FL
Criteria for obesity and MetS
ethnic differences
◼ Only 2-3 of Asians classified as obesity by Western criteria
◼ All Asian populations studied had a higher BF at a lower BMI compared to Caucasians
◼ For the same BF their BMI was 3-5 units lower compared to Caucasians
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Consensus of management of FLD by
Chinese Society of Medicine
① Guideline for the diagnosis of
NAFLD and ALD
Chin J Hepatol 2001 amp 2003
② Guidelines for diagnosis and
treatment of NAFLD amp ALD
J Dig Dis 2008 9108-116
③ Chinese Guidelines for
diagnosis and management of
NAFLD amp ALD update 2010
J Dig Dis 2011 12 38-50
40
Definition of NAFLD
◼ There is evidence of hepatic steatosis either by
imaging or by histology and no causes for
secondary steatosis
NAFLD is a highly prevalent form of FLD
caused by over-nutrition
NAFLD is an acquired metabolic stress-
induced liver diseases associated with insulin
resistance and genetic susceptibility
Fatty liver in general population in China
CityYear Prevalence Etiology Others
Shanghai2005 173 AFL 08 NAFL 15
Other 12
Drinking 13
Guangzhou2007 145 AFL 05 NAFL 117
Other 18
Children 13
Xirsquoan2008 136 AFL 87 () NAFL 147 Drinking 66
Chengdu2009 125 AFL 26 NAFL 63
Other 36
Beijing2013 351 AFL 41 NAFL 313
Shanghai2014 37218810(40-70 yrs in
Chongming Island)
NAFLD 422 276 in NGT 457 in
pre-diabetes 625 in
diabetes persons
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87
Li HBPD Int 20098377-82Yan JGH 2013 281654-9 Yang Z Sci Rep 2016637886
Prevalence of Fatty Liver in Shanghai Adults
◼ Total 17◼ Male 19
◼ Female 15
◼ NAFLD 15
◼ AFL 08
◼ Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
57
NAFLD 88
AFLMixed FL
Criteria for obesity and MetS
ethnic differences
◼ Only 2-3 of Asians classified as obesity by Western criteria
◼ All Asian populations studied had a higher BF at a lower BMI compared to Caucasians
◼ For the same BF their BMI was 3-5 units lower compared to Caucasians
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Consensus of management of FLD by
Chinese Society of Medicine
① Guideline for the diagnosis of
NAFLD and ALD
Chin J Hepatol 2001 amp 2003
② Guidelines for diagnosis and
treatment of NAFLD amp ALD
J Dig Dis 2008 9108-116
③ Chinese Guidelines for
diagnosis and management of
NAFLD amp ALD update 2010
J Dig Dis 2011 12 38-50
40
Definition of NAFLD
◼ There is evidence of hepatic steatosis either by
imaging or by histology and no causes for
secondary steatosis
NAFLD is a highly prevalent form of FLD
caused by over-nutrition
NAFLD is an acquired metabolic stress-
induced liver diseases associated with insulin
resistance and genetic susceptibility
Fatty liver in general population in China
CityYear Prevalence Etiology Others
Shanghai2005 173 AFL 08 NAFL 15
Other 12
Drinking 13
Guangzhou2007 145 AFL 05 NAFL 117
Other 18
Children 13
Xirsquoan2008 136 AFL 87 () NAFL 147 Drinking 66
Chengdu2009 125 AFL 26 NAFL 63
Other 36
Beijing2013 351 AFL 41 NAFL 313
Shanghai2014 37218810(40-70 yrs in
Chongming Island)
NAFLD 422 276 in NGT 457 in
pre-diabetes 625 in
diabetes persons
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87
Li HBPD Int 20098377-82Yan JGH 2013 281654-9 Yang Z Sci Rep 2016637886
Prevalence of Fatty Liver in Shanghai Adults
◼ Total 17◼ Male 19
◼ Female 15
◼ NAFLD 15
◼ AFL 08
◼ Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
57
NAFLD 88
AFLMixed FL
Criteria for obesity and MetS
ethnic differences
◼ Only 2-3 of Asians classified as obesity by Western criteria
◼ All Asian populations studied had a higher BF at a lower BMI compared to Caucasians
◼ For the same BF their BMI was 3-5 units lower compared to Caucasians
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Definition of NAFLD
◼ There is evidence of hepatic steatosis either by
imaging or by histology and no causes for
secondary steatosis
NAFLD is a highly prevalent form of FLD
caused by over-nutrition
NAFLD is an acquired metabolic stress-
induced liver diseases associated with insulin
resistance and genetic susceptibility
Fatty liver in general population in China
CityYear Prevalence Etiology Others
Shanghai2005 173 AFL 08 NAFL 15
Other 12
Drinking 13
Guangzhou2007 145 AFL 05 NAFL 117
Other 18
Children 13
Xirsquoan2008 136 AFL 87 () NAFL 147 Drinking 66
Chengdu2009 125 AFL 26 NAFL 63
Other 36
Beijing2013 351 AFL 41 NAFL 313
Shanghai2014 37218810(40-70 yrs in
Chongming Island)
NAFLD 422 276 in NGT 457 in
pre-diabetes 625 in
diabetes persons
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87
Li HBPD Int 20098377-82Yan JGH 2013 281654-9 Yang Z Sci Rep 2016637886
Prevalence of Fatty Liver in Shanghai Adults
◼ Total 17◼ Male 19
◼ Female 15
◼ NAFLD 15
◼ AFL 08
◼ Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
57
NAFLD 88
AFLMixed FL
Criteria for obesity and MetS
ethnic differences
◼ Only 2-3 of Asians classified as obesity by Western criteria
◼ All Asian populations studied had a higher BF at a lower BMI compared to Caucasians
◼ For the same BF their BMI was 3-5 units lower compared to Caucasians
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Fatty liver in general population in China
CityYear Prevalence Etiology Others
Shanghai2005 173 AFL 08 NAFL 15
Other 12
Drinking 13
Guangzhou2007 145 AFL 05 NAFL 117
Other 18
Children 13
Xirsquoan2008 136 AFL 87 () NAFL 147 Drinking 66
Chengdu2009 125 AFL 26 NAFL 63
Other 36
Beijing2013 351 AFL 41 NAFL 313
Shanghai2014 37218810(40-70 yrs in
Chongming Island)
NAFLD 422 276 in NGT 457 in
pre-diabetes 625 in
diabetes persons
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87
Li HBPD Int 20098377-82Yan JGH 2013 281654-9 Yang Z Sci Rep 2016637886
Prevalence of Fatty Liver in Shanghai Adults
◼ Total 17◼ Male 19
◼ Female 15
◼ NAFLD 15
◼ AFL 08
◼ Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
57
NAFLD 88
AFLMixed FL
Criteria for obesity and MetS
ethnic differences
◼ Only 2-3 of Asians classified as obesity by Western criteria
◼ All Asian populations studied had a higher BF at a lower BMI compared to Caucasians
◼ For the same BF their BMI was 3-5 units lower compared to Caucasians
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Prevalence of Fatty Liver in Shanghai Adults
◼ Total 17◼ Male 19
◼ Female 15
◼ NAFLD 15
◼ AFL 08
◼ Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
57
NAFLD 88
AFLMixed FL
Criteria for obesity and MetS
ethnic differences
◼ Only 2-3 of Asians classified as obesity by Western criteria
◼ All Asian populations studied had a higher BF at a lower BMI compared to Caucasians
◼ For the same BF their BMI was 3-5 units lower compared to Caucasians
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Criteria for obesity and MetS
ethnic differences
◼ Only 2-3 of Asians classified as obesity by Western criteria
◼ All Asian populations studied had a higher BF at a lower BMI compared to Caucasians
◼ For the same BF their BMI was 3-5 units lower compared to Caucasians
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Modified definition for Asians
Three or more of the following
Central obesity andor obesity Waistline gt90 cm (M) gt80 cm (F) andor BMI gt 25 kgm2
Hypertriglyceridaemia TG ge17 mmolL
Low HDL-C lt103 mmolL (M) lt129 mmolL (F)
High blood pressure ge13085 mmHg
High fasting glucose FPG ge 61 mmolL
Fan JG amp Pen YD HBPT Int 2007
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Fan JG World J Gastroenterol 2008 142418-24
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Prevalence of NAFLDNASH in Shanghai
◼ Both prevalence of MetS and NAFLD was 153 in Shanghai adults in 2003
◼ In NAFLD prevalence of MetS and abnormal ALT
was 529 and 127 respectively
◼ Prevalence of NASH might be between 19 and
41 in Shanghai adults
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
010
2030405060
708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
Fan JG J Gastroenterol Hepatol 2005 with some data unpublished
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Lean NAFLD is more common in Asia
0
5
10
15
20
25
USA
(Younossi
2012)
KOREA (Cho
HC 2016)
KOREA (Kim
HJ 2004)
INDIA (Das
K 2010)
China (Fan
2007)
Pre
vale
nce
of
Lean
NA
FLD
Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Prevalence of NASH in Shanghai
Bao-Steel Company A total of 59131 employees of Shanghai Bao-Steel Company
were undergone biannual health check-up
Prevalence of abnormal ALT was 46 without obvious
changes between 1995 and 2002
Prevalence of fatty liver in patients with abnormal ALT was
increased between from 259 to 514
Prevalence of NAFLD among 14646 subjects was 131 in
2002 percentage of abnormal ALT among NAFLD patients
was 164
Prevalence of NASH might be around 22 in health
check-up adults in 2002
Fan JG J Gastroenterol Hepatol 2007 with some data unpublished
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Incidence of NAFLD in Shanghai
◼ 5226 non-drinking workers without US-fatty liver at
baseline
◼ After 2-year follow-up 310 pts (62) were found to
have NAFLD
◼ Incidence of NAFLD (3 new cases100 people year) is equal to
that in Dionysos study
◼ The baseline BMI serum triglyceride and their subtle
gain during follow-up were independent predictors of
incident of NAFLD Fan JG et al Hepatol International 2010
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Impact of BMI on incidence and
remission of NAFLD
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
-10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou Chellip Fan JG Chin J Intern Med 2012 Chin J Hepatol 2010
136 (60440) NAFLD was recovery at the end of 2-year follow-up
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Increased prevalence of obesity in Asia
0
1
2
3
4
5
6
7
8
2000 2005 2010 2014
China
Japan
Korea
India
Indonesia
Year
Fan JG et al J Hepatol 2017
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Global prevalence of NAFLD
Younossi Z et al Gastroenterology20161501778-85
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Wang FS Fan JG et al Hepatology 2014 602099-2108
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Etiology of fatty liver in liver clinic in Shanghai
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
Percent of abnormal ALT
000
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
NAFLD AFL HBV with FL DILI-FL
Percent
Percent of NASH might be 20 in out-patients with NAFLD
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Liver biopsy from 11 year old male with
abnormal LFTs
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
0
20
40
60
80
100
steatosis（123） ballonning
degeneration （yn）
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2
Percent of NASH in biopsy-proven NAFLD was 414
Advanced fibrosis was 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012 13588-95
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
CharacteristicsNAFLD
(n=101)
None-NASH
(n=15)
Borderline NASH
(n=32)
Definitive
NASH
(n=54)
P
Steatosis graden () lt0001
S1 (5-33) 32 (317) 15 (100) 15 (469) 2 (37)
S2 (34-66) 45 (446) 0 17(531) 28(519)
S3 (gt66) 24 (238) 0 0 24(444)
Fibrosis stage n () lt0001
F0 18 (178) 7(467) 9(281) 2(37)
F1 44 (436) 5(333) 21(656) 18(333)
F2 26 (257) 1(67) 1(31) 24(444)
F3 10 (99) 2 (133) 1(31) 7(130)
F4 3 (30) 0 0 3 (56)
Histological changes of 101 patients with NAFLD
Percent of NASH and cirrhosis was 54 and 3 respectively
Both were associated with T2DM and MetS Shen F hellipFan JG Liver Int 2015 35 2392-400
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Study profile of NAFLD across the Asia Pacific region ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Percentage of patients with NASH
by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Percentage of patients with advanced
fibrosis by country ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Independent factors discriminating the different
histological subgroups ndash the GO ASIA initiative
Chan WK hellipFan JGhellip Wong VWS Aliment Pharmacol Ther 2018 47816-825
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Normal liver NAFL NASH plusmn fibrosis Cirrhosis
Annual incidence of NAFLD 3-4
60 can reverse NAFLD by lifestyle intervention
25 progress from NAFL to NASH and have fibrosis progression in 3 yrs
Spontaneous reversal of NASH uncommon without intervention
Fibrosis progression 1 stage in 7 yrs in NASH 1 stage in 14 yrs in NAFL
No data on reversal of cirrhosis
HCC
bull Absence of cirrhosis reported in 30-50 of NAFLD-associated HCC in Asians
bull The absolute risk of HCC in non-cirrhotic patients is lt01 per year
bull 1-4 per year
Fan JG Kim SU Wong WS J Hepatol 2017
Natural history of NAFLD according to data from Asia
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
NAFLD leads to liver cancer do we
have sufficient evidence
Duan XY Qiao L Fan JG Cancer letter 2014
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
wwwchzfgcom 32
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
01020304050607080
Obesity
Hypertension
High TG
high TC
Diabetes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hypertension
high TG
high TC
Diabetes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
上海宝钢队列糖尿病发病率与危险度比
基线特征 DM发病数DM发病率（）
危险度比（HR）
95 CI下限 95 CI上限
肥胖 BMI ＜25 kgm2 215 41 1 - -
BMI ge25 kgm2 155 114 241 195 298
IFG （-） 233 395 1 - -
（+） 147 1561 367 297 452
高TG血症 （-） 197 405 1 - -
（+） 173 10 216 175 265
高TC血症 （-） 311 516 1 - -
（+） 59 1046 143 104 195
脂肪肝 （-） 322 505 1 - -
（+） 48 2286 407 3 551
高Hb血症 （-） 320 532 1 - -
（+） 50 873 125 092 17
Fan JG et al J Diabetes Investig 2016 7206-211
N=12438follow-up 6 years
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
上海崇明脂肪肝流行病学调查◼ Circulating periostin in relation to insulin resistance and
NAFLD among overweight and obese subjects Sci Rep
2016637886
◼ Plasma selenium levels and NAFLD in Chinese adults a
cross-sectional analysis Sci Rep 2016 637288
◼ Plasma osteoprotegerin levels are inversely associated with
NAFLD in patients with type 2 diabetes A case-control study
in China Metabolism 2016 65(4)475-81
◼ Association of calf circumference with insulin resistance and
NAFLD the REACTION study BMC Endocr Disord
201717(1)28
◼ Impaired lung function is associated with NAFLD
independently of metabolic syndrome features in middle-aged
and elderly Chinese BMC Endocr Disord 2017 17(1)18
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Fatty liver amp HBV infection in Chinese
◼ Inverse association between HBsAg+ve and
ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
◼ Inverse association between HBV infection and
MRS-diagnosed fatty liver in Hong Kong adults
Wong VWS et al J Hepatol 2012
◼ Inverse association between HBV infection and
hypertriglyceridemia and MetS Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J
Hepatol 2012
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Ye DW hellipFan JG et alAASLD2009
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Fan JG et al AASLD 2016
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Fatty liver amp CHB in Our Group① Hepatitis B and fatty liver causal or coincidental J Gastroenterol Hepatol 2008 23(5)679-81
② Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese
patients with CHB infection J Gastroenterol Hepatol 2008 231419-25
③ Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic
mice model J Gastroenterol Hepatol 2012 271858-64
④ Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with
Virological Factors Dig Dis Sci 2014 592571-9
⑤ Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4
Mediated Innate Immune Response Hepat Mon 2015 15e27909
⑥ CAP for noninvasive assessment of hepatic steatosis using Fibroscan Validation in chronic
hepatitis B Dig Dis Sci 2015 60243-51
⑦ Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects J
Gastroenterol Hepatol 2015 301753-1758
⑧ Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in
chronic hepatitis B World J Gastroenterol 2015 218605-8614
⑨ PNPLA3 rs1010023 predisposes CHB to hepatic steatosis but improves insulin resistance and
glucose metabolism J Diabetes Res 2017 20174740124
⑩ Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and
CHB Sci Rep 2017 710517
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
OverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291
Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
NAFLD is not just a lsquoWesternrsquo problem
◼ Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China
◼ Fatty liver is more often associated with obesity than with alcoholism
◼ Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well
◼ Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome
◼ NAFLD is emerging into a new and major health problem in Chinese
Fan JG J Hepatol 2009 JGH 2013
Thanks for your attentionThanks for your attention
Thanks for your attentionThanks for your attention
