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Implications of PNPLA3 polymorphism in chronic hepatitis C patients receiving peginterferon plus ribavirin
Alimentary Pharmacology and Therapeutics, 04/30/2012
Clinical Article
Valenti L et al. – PNPLA3 p.148M/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.148M/M PNPLA3 genotype unmasked an association between IL28BCC genotype and more severe liver fibrosis.
Methods- In this observational study, the authors considered 602 treatment-naive consecutive patients from tertiary referral centres in Milan and Vienna [61% genotype 1 (G1), 30% advanced fibrosis, 33% IL28B rs12979860 CC].
- The p.148M/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, IL28BCC genotype, treatment dose, and steatosis, p.148M/M remained a predictor of SVR in G1/4 patients with advanced fibrosis (OR 0.23, 95% CI 0.04-0.87).
- The p.148M/M genotype was associated with more advanced fibrosis in the overall series (P=0.049), whereas the rs12979860 IL28BCC genotype only in patients negative for p.148M/M (P=0.017), independently of age, BMI and alanine transaminase levels (OR 1.51, 95% CI 1.01-2.27).