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Implications of PNPLA 3 polymorphism in chronic hepatitis C patients receiving peginterferon plus ribavirin
Author(s) -
Valenti L.,
Aghemo A.,
Stättermayer A. F.,
Maggioni P.,
Nicola S.,
Motta B. M.,
Rumi M. G.,
Dongiovanni P.,
Ferenci P.,
Colombo M.,
Fargion S.
Publication year - 2012
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2012.05109.x
Subject(s) - ribavirin , medicine , hepatitis c , virology , hepacivirus , chronic hepatitis , gastroenterology , pharmacology , hepatitis c virus , virus
Summary Background Homozygosity for the PNPLA 3 p. I 148 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 M ilan and V ienna [61% genotype 1 ( G 1), 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 G 1/4 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 G 1/4 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 G 1/4 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.