A potential role of Helicobacter pylori infection in nonalcoholic fatty liver disease

S. A. Polyzos, D. Chatzopoulos, J. Moschos, A. Papatheodorou, K. Patsiaoura, E. Katsiki, E. Zafeiriadou,

C. Zavos, K. Anastasiadou, E. Terpos, J. Kountouras

• Hp infection and chronic liver diseases are strongly linked

• Hp-like DNA is more commonly found in liver samples from

chronic liver disease patients than from controls

Helicobacter pylori (Hp) and liver

Leone N, et al. Cancer Detect Prev 2003;27:494-7Polyzos SA, et al. Metabolism 2013;62:121-6

Pirouz T, et al. Dig Dis Sci 2009;54:1456-9

• Affects 25-30% of the population in western countries• NAFLD sequence:

• Fatty liver• Non-alcoholic steatohepatitis (NASH) • Liver fibrosis • Cirrhosis - HCC

Non-alcoholic fatty liver disease (NAFLD)

• Limited clinical data• Recent Japanese study evaluated Hp infection in patients with NAFLD

and its association with disease severity

• 130 NAFLD patients (biopsy proven)• 43 with NAFL • 87 with NASH

• Glucose tolerance • Liver biopsies were scored for:

• NAFLD activity score (NAS) • Fibrosis• Iron deposits

Hp and NAFLD

Sumida Y, et al. J Gastroenterol 2015 Jan 28.

Results

• Hp IgG seropositivity: 40%

• The prevalence of NASH: significantly higher in patients with Hp IgG

seropositivity (81%) than in those without (58%, p = 0.008)

• Glucose intolerance was similar between the two groups

• The total NAS and the grade of hepatocyte ballooning were higher in

patients with Hp IgG seropositivity

• Hepatic iron grade was lower in patients with Hp IgG seropositivity

Sumida Y, et al. J Gastroenterol 2015 Jan 28.

Univariate and multivariate analyses to identify independent variables associated with NASH

NAFIC score: NASH, Ferritin, Insulin, type IV Collagen 7 s(used in Japan to differentiate NASH from NAFL)

• The association of Hp seropositivity with hepatocyte ballooning

suggests that Hp infection may represent another contributing

factor in the progression from NAFL to NASH

Thus…

Sumida Y, et al. J Gastroenterol 2015 Jan 28.

• To evaluate • Hp infection in patients with NAFLD • its association with disease severity

Aim of OUR study

• 28 patients with biopsy proven NAFLD • 15 with NAFL• 13 with NASH

• 25 matched healthy controls

• Blood samples for anti-Hp IgG and standard biochemical tests were

obtained after overnight fasting

• 13C urea breath test was performed before liver biopsy in NAFLD

group

Patients and methods

ResultsComparative data of study groups

Hp-related data in control and NAFLD groups

• Hp infection (assessed by history of Hp eradication treatment

and/or Hp IgG seropositivity) (p=0.034)

and • log(HOMA-IR) (p=0.007)

could independently predict NAFLD

Logistic regression analysis

Hp-related data in NAFL and NASH subgroups

There were no significant differences in: • steatosis grade • fibrosis• lobular or portal inflammation, or ballooning

when NAFLD patients were divided according to Hp IgG

seropositivity or 13C urea breath test positivity

Results

• NAFLD vs. non-NAFLD individuals had: • higher anti-Hp IgG titers• lower circulating adiponectin• higher TNF-α levels

which all contribute to NAFLD pathogenesis

• Therefore, Hp infection may represent one more hit contributing to

the pathogenesis of NAFLD, though not to the progression from

NAFL to NASH

Discussion - Conclusions

• NAFLD, closely related to IR

• Our systematic review:• Hp infection and IR are associated and involved in the

pathophysiology of MetS-related with NAFLD

Discussion - Conclusions

Polyzos SA, Kountouras J, Zavos C, Deretzi G. Metabolism 2013;62:121-6Kountouras J, Polyzos SA, Zavos C, et al. Hepatology 2014,60:1450-1

• Although Hp eradication had no long-term effect on hepatic steatosis, a

trend towards improvement was observed in: • NAFLD fibrosis score and • HSENSI

• Homocysteine <12.5 μmol/L • Serum glutamic oxaloacetic transaminase ≥37 U/L• Erythrocyte sedimentation rate ≥20 mm• Nonalcoholic Steatohepatitis Index

thereby warranting further relative investigation with larger studies using

paired biopsies

Discussion - Conclusions

Polyzos SA, et al. Arq Gastroenterol 2014;51:261-8

•These results warrant further validation

•If confirmed, eradicating Hp infection may have relative

therapeutic perspectives in NAFLD treatment

Taken together…

21ST CONGRESS OF HELICOBACTER PYLORI AND

OTHER BACTERIAL INFECTIONS OF GI TRACT

Athens, March 2016