The Global Burden of Hepatitis Infection

Prof. Henry LY ChanMBChB (CUHK), MD (CUHK), FRCP (Edin, Lond)

Head, Division of Gastroenterology and Hepatology

Director, Institute of Digestive Disease

Director, Center for Liver Health

Assistant Dean (Development), Faculty of Medicine

The Chinese University of Hong Kong

HCV distribution across the world

* Estimated number of chronically infected individuals (2010)

Lavanchy D. Clin Microbiol Infect 2011; 17:107–115;CDC: http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to-travel/hepatitis-c.htm.

Prevalence of HCV >10%5–10%2–5%

<1%No data

Africa28 M*

Americas14 M*

Europe18 M*

130–170 million people world wide are infected with HCV

Middle East16 M*

1–2%

China30 M

S. Korea 0.8 M

Japan3 M

N. Korea0.2 M

Australia0.2 M

India18 M

Indonesia9 M

Prevalence of HCV in Asia-Pacific countries

• Prevalence = % anti-HCV (2010); • HCC = hepatocellular carcinoma.

Lavanchy D. Clin Microbiol Infect 2011; 17:107–115;

Lee MH, et al. Gut 2011; 60:688–694;

Prev

alen

ce o

f HCV

(%)

Australi

a

New Zeala

ndChina

Japan

North Korea

South

Korea

Mongo

lia

Pakist

anIndia

Indonesia

Thailan

d

Vietnam

Singa

pore

Cambodia

Mala

ysia

0

2

4

6

8

10

12

1.10.3

2.2 2.4

1.01.7

10.7

5.9

1.5

3.9

2.21.0 1.0

4.1

1.5

0 10 20 30 400

20

40

60HCV (n=33,121)

The burden of HCV

• Major burden comes from sequelae from chronic infection

• HCV-related mortality and morbidity mainly due to cirrhosis and HCC

• Estimated to be the cause of 27% of cirrhosis and 25% of HCC worldwide2

• South-East Asia ~ 75% unaware they are infected until they have symptoms of cirrhosis/HCC3

1. Grebely J & Dore G. Semin Liver Dis. 2011; 31:331–339;

2. Perz JF, et al. J Hepatol 2006; 45:529–538;

3. WHO Prevention and control of viral hepatitis infection:http://who.int/csr/disease/hepatitis/GHP_Framework_En.pdf?ua=1.

Risk of HCV-related cirrhosis increasesexponentially by duration of infection1

Years

Cirr

hosi

s (%

)

The disease burden will continue to grow as the chronically infected population ages

•

Sherman K. 2006. http://www.fda.gov;Di Bisceglie AM, et al. Hepatology 2000; 31:1014–1018.

HCV exposure

Transplant/death 3–4%/yr

Cirrhosis20%

Chronic 85%

Time(years) 10 3020

HCC4%/yr

Alcohol use, obesity, co-infection with HIV or HBV accelerate HCV progression

ESLD6%/yr

Resolved15%

% = percent of original group.

Patterns of age-specific HCV prevalence and HCV burden

Hajarizadeh B, et al. Nat Rev Gastroenterol Hepatol 2013; 10:553–562.

Age-specific prevalence of HCV infection and incidence of HCV-related advanced liver disease in four representative countries

Prev

alen

ce (%

)

Inci

denc

e of

HCV

-rel

ated

adv

ance

dliv

er d

isea

ses

YearAge (years)

<19 20–29 30–39 40–49 50–59 60–690

10

20

30

40

1980 1990 2000 2010 2020 2030

EgyptJapanAustraliaUSA

Proportion of patients with HCV and HCC in Asia-Pacific countries

• Yuen MF, et al. J Gastroenterol Hepatol 2009; 24:346–353;1. Venook AP, et al. The Oncologist 2010; 15:5–13.

Country/region HCV-related HCC, %

Japan 79

Australia 30–40

New Zealand 30–40

South Korea 20

India 16

Thailand 15

Singapore 13–20

Mainland China 12

Hong Kong 3–6

Philippines 4

Malaysia 2

US Canada LatinAmerica

WesternEurope

Cent/EasternEurope

Nordic Asia/Pacific

Mid. East/Africa

0

2

4

6

8

10

Patient Provider Government Payer

Barriers to HCV treatment by global region: physician perspective

* Each barrier rated on a 10-point Likert scale, from 0 “not a barrier” to 10 “large barrier”

McGowan CE, et al. Hepatology 2013; 57:1325–1332.

1. Medication expense

3. Treatment duration

2. Fear of side effects

Mea

n lik

ert s

core

*

Need to consider effectiveness for the entire HCV population

Ipsos HCV Monitor Q2 2013, Gilead press release 2014.

Zhuang H, Asian Pacific Perspective in Hepatitis 2011, Vietnam

Diagnosed:~ 745,000

Treated:~ 5%

~ 68%

Japan

HCV prevalence: ~ 1.1 million

Diagnosed:~ 158,000

Treated:~ 1.6%

~ 1.6%

HCV prevalence: ~ 10 million

China

Diagnosed:~ 1.6 million

Treated:~ 5.5%

~ 38%

USA

HCV prevalence: ~ 4.1 million

>7%2%-7%<2%

Adopted and modified from CDC website: http://www.cdc.gov/Features/dsHepatitisAwareness/

Worldwide burden of HBV

• >350 million are chronic HBV carriers

• In the 2010 Global Burden of Disease study, HBV infection was the 10th leading cause of death (786 000 deaths per year).

• About half the total liver cancer mortality in 2010 was attributed to HBV infection

• From 1990 to 2010, the worldwide mortality associated with liver cancer increased by 62%, and that associated with cirrhosis increased by 29%.

Trepo, Chan and Lok. Lancet 2014 (in press)

HBV infection in Asia

• 74% of HBV carriers are in Asia Pacific countries

• Among 260 million HBV infected people in Asia, 160 million resides in Western Pacific region

• In Western Pacific region– 50% of all HBV patients in the world– 60% of HCC in the world– 360,000 people died of HBV-related liver disease annually

WHO. Prevention & Control of Viral Hepatitis Infection: Framework for Global Action. 2012. Available: http://www.who.int/csr/disease/hepatitis/Framework/en/index.html

HBV Infection is the Commonest Cause of HCC in Asia

Singapore Philippines India Korea Taiwan Hong Kong Thailand Malaysia0%

20%

40%

60%

80%

100%

APWP-HCC, Hong Kong, June 2008

Pro

port

ion

of H

CC

cau

sed

by H

BV

Universal vaccination to newborn

• First launched 1984 in Taiwan• Now 180 (3%) countries in the world has this program

• Prevalence of HBsAg positivity in Taiwan 2009 after 25 years of vaccination program = 0.9%

Age <25 25 26-27 28-29

N 2857 97 199 179

% 0.9 6.2 6.0 10.6

Ni YH, et al. J Hepatol 2012;57:730-5

Prevention of HBV infection: impact of vaccination in Taiwan

1981–86 1986–90 1990–94 2007

Average annual incidence of HCC in children aged 6–14 years (per 100,000) 0.7 0.57 0.36 0.19

Adapted from 1. Lin HH, et al. J Med Virol 2003;69:471–474. 2. Chang MH, et al. N Engl J Med 1997;336:1855–9.3. Chen DS. Hepatol Res 2007;37(Suppl. 2):S101–5

1980 1990 2000 2010 2020 2030 2040

HBsAgcarriage

Chronichepatitis

Cirrhosis and HCC

HBV vaccination programmelaunched in 1984

By end of 2011, 180 countries has universal vaccination programme47 European countries have universal vaccination; 6 (Denmark, Finland, Iceland, Norway, Sweden and UK) have targeted vaccination

Trepo, Chan and Lok. Lancet 2014 (in press)

Reimbursement policies differ across Asia-Pacific countries

Low reimbursement Partial reimbursement High reimbursement

Lamivudine is most commonly used

Entecavir & Tenofovirare most

commonly used

Drug use according to reimbursement policy

Drug resistance High cost

Thailand, Indonesia, Philippines, Vietnam

Japan, Singapore, Australia, New Zealand

Hong Kong, Taiwan, Korea, China

The increasing problem of HBV drug resistance in Asia

794 patients receiving sequential/combination NUCs• Diverse drug mutations found in 306 (38.5%)• ETV-R ±LAM-R ±ADV-R in 45 (5.7%)

0

10

20

30

40

50

60

70

80

90

100

En

teca

vir

resi

stan

t m

uta

tio

ns

(%)

10%

29%

40%

24%

LAM LAM+ADVETV+ADV

(n=1)

LAMADV(n=136)

LAMETV(n=35)

LAMADVLAM+ADV

(n=5)

LAMADVETV(n=38)

ADVLdT(n=8)

LAM LAM+ADV

(n=32)

LAMADVLdT+ADV

(n=2)

3%

25%

100% 100%

Adapted from Liu Y, et al. J Viral Hepat 2011;18:e29-39.

Summary

Large global burden of HBV and HCV infection in the world.

Key cause of hepatocellular carcinoma and mortality

HCV• Great advances in antiviral therapy• Challenges in accessibility and affordability of medicine

HBV• Vaccination has significantly reduced burden in the younger

generation• Challenges in accessibility of vaccine and antiviral therapy for

existing patients