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

Background Homozygosity for the PNPLA3 p. I148 M polymorphism influences steatosis and fibrogenesis in chronic hepatitis C ( CHC). Aim To evaluate the effect of p.148 M/ M on sustained virological response ( SVR) and viral kinetics in patients who underwent antiviral therapy with peg-interferon and ribavirin, stratified according to viral genotype and fibrosis severity, and secondarily, the interaction with interleukin- 28 B ( IL28B) genotype on liver damage. Methods In this observational study, we considered 602 treatment-naïve consecutive patients from tertiary referral centres in Milan and Vienna [61% genotype 1 ( G1), 30% advanced fibrosis, 33% IL28B rs12979860 CC]. Results The p.148 M/ M genotype, detected in 8% of patients, did not influence SVR in the overall series ( P = 0.29), but it was associated with SVR (3/17, 17% vs. 56/121, 46%; P = 0.034) and complete early viral response (4/17, 23% vs. 68/121, 56%; P = 0.018) in G1/4 patients with advanced fibrosis. After adjustment for age, viral load, IL28B CC genotype, treatment dose, and steatosis, p.148 M/ M remained a predictor of SVR in G1/4 patients with advanced fibrosis ( OR 0.23, 95% CI 0.04-0.87). The p.148 M/ M genotype was associated with more advanced fibrosis in the overall series ( P = 0.049), whereas the rs12979860 IL28B CC genotype only in patients negative for p.148 M/ M ( P = 0.017), independently of age, BMI and alanine transaminase levels ( OR 1.51, 95% CI 1.01-2.27). Conclusions PNPLA3 p.148 M/ M genotype was negatively associated with SVR and early viral kinetics independently of steatosis, albeit only in difficult-to-cure G1/4 patients with advanced fibrosis, whereas stratification for the p.148 M/ M PNPLA3 genotype unmasked an association between IL28B CC genotype and more severe liver fibrosis. [ABSTRACT FROM AUTHOR]