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Implications of PNPLA3 polymorphism in chronic hepatitis C patients receiving peginterferon plus ribavirin

L Valenti1, A Aghemo, A F Stättermayer

  • 1Department of Internal Medicine, Università degli Studi, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy. luca.valenti@unimi.it

Alimentary Pharmacology & Therapeutics
|April 26, 2012
PubMed
Abstract

Insights

The PNPLA3 p.I148M polymorphism impacts sustained virological response (SVR) in chronic hepatitis C patients. Homozygosity for the p.148M/M genotype predicts lower SVR in difficult-to-treat patients.

Area of Science:

  • Hepatology
  • Genetics
  • Virology

Background:

  • The PNPLA3 p.I148M polymorphism is a known factor influencing liver steatosis and fibrogenesis in chronic hepatitis C (CHC).
  • Understanding genetic influences is crucial for optimizing antiviral therapy outcomes in CHC patients.

Purpose of the Study:

  • To assess the impact of the PNPLA3 p.148M/M genotype on sustained virological response (SVR) and viral kinetics.
  • To evaluate these effects in patients treated with peg-interferon and ribavirin, stratified by viral genotype and fibrosis severity.
  • To investigate the secondary interaction between PNPLA3 genotype and interleukin-28B (IL28B) genotype on liver damage.

Main Methods:

  • Observational study of 602 treatment-naïve CHC patients from Milan and Vienna.
  • Genotyping for PNPLA3 p.I148M and IL28B rs12979860 polymorphisms.
  • Stratification by viral genotype (61% genotype 1), fibrosis severity (30% advanced), and IL28B CC genotype (33%).

Main Results:

  • The PNPLA3 p.148M/M genotype (8% of patients) did not affect SVR overall but was linked to lower SVR and early viral response in genotype 1/4 patients with advanced fibrosis.
  • After adjustments, p.148M/M remained a predictor of reduced SVR in this specific subgroup (OR 0.23).
  • p.148M/M was associated with more advanced fibrosis, while IL28B CC genotype showed this association only in patients without p.148M/M.

Conclusions:

  • The PNPLA3 p.148M/M genotype negatively impacts SVR and early viral kinetics, particularly in difficult-to-treat genotype 1/4 CHC patients with advanced fibrosis.
  • Stratification revealed an association between IL28B CC genotype and more severe liver fibrosis when PNPLA3 p.148M/M was absent.
  • These findings highlight the complex interplay of genetic factors in CHC treatment response and disease progression.

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