Interferon lambda-3 is not associated with clinical outcome in patients with HCV-induced compensated cirrhosis: A long-term cohort study

Background: Interferon Lambda-3 (IFN-lambda 3) gene polymorphism is associated with spontaneous clearance of hepatitis C virus (HCV) and response to IFN-based therapy (IFN). However, very few data are available about its value in predicting sustained virologic response (SVR) in patients with cirrhosis, and whether IFN-lambda 3 genotype influences liver disease progression remains unclear. Methods: We determined IFN-lambda 3 genotype by PCR in a cohort of patients with compensated HCV-related cirrhosis, enrolled between 1989 and 1992. Person-years follow-up was calculated for each individual from the date of enrolment to the development of first episode of decompensation, HCC, liver transplant, death or end of follow-up. The follow-up of patients who achieved SVR was censored at the time of IFN initiation. Kaplan-Meier curves and Cox regression analyses were used to assess the association between IFN-lambda 3 genotype and clinical outcome. Results: IFN-lambda 3 was determined in 264 patients (52% males, mean age 57 +/- 8 years, 67% HCV genotype (G)1, while CC, CT and TT genotypes were 36%, 50% and 14%, respectively. During a median follow-up of 14.8 years, 149 (56%) patients received IFN. Overall, SVR was achieved in 31(21%) patients, 40% among those with CC genotype (22% in G1 and 61% in G2, respectively) compared to 10% and 13% among patients with CT and TT genotypes (p < 0.0001). Univariate and multivariate analyses found no association between IFN-lambda 3 (CC vs. non-CC genotype) and disease progression. Conclusion: IFN-lambda 3 determination is fundamental for allocating cirrhotic patients to be treated with IFN, while it has no value in predicting the outcome of the disease. (C) 2014 Elsevier B.V. All rights reserved.