Treatment with PEG-IFN and ribavirin in patients with chronic hepatitis C, low grade of hepatic fibrosis, genotype 1 and 4 and favorable IFNL3 genotype: A pharmacogenetic prospective study.

The new direct-acting antivirals agents (DAAs) rapidly changed the treatment approach in chronic hepatitis C (CHC); however, the interferon (IFN)-free therapies availability is currently different in some countries, due to higher costs of these drugs. Naïve treated patients, who are not eligible for IFN-free therapies, could be selected for standard dual treatment with pegylated (PEG)-IFN and ribavirin (RBV), through IFN lambda 3 gene polymorphisms and fibrosis stage evaluation. Inclusion criteria were: naïve treated CHC patients with GT1 or GT4, without major contraindication to PEG-IFN or RBV, with fibrosis stage F0-F2 and IFNL3 rs8099917/rs12979860 TT/CC genotypes. 65 patients were included in the study. Overall SVR was observed in 50 patients (76.9%); SVR rates among different genotypes were as follows: 15 with GT1a (71.4%), 27 with GT1b (79.4%) and 8 for GT4 (80%). The RBV cutoff at 2weeks of 1800ng/mL, predictor of RVR, was determined (p=0.003; sensibility=60.4%, specificity=88.2%, positive predictive value=88.9%, negative predictive value=100%). In multivariate analysis, factors significantly associated with treatment failure were living alone condition (OR=4.302; 95%IC=1.254-16.257; p=0.034) and RBV plasma level <1800ng/mL at 2weeks (OR=4.970; 95%IC=1.405-17.565; p=0.009). Considering a pharmacogenetic-guided approach, dual therapy with PEG-IFN and RBV can be considered a reliable option for patients ineligible for IFN-free treatments, who are motivated and well informed about all the aspects related to PEG-IFN administration.
(Copyright © 2017. Published by Elsevier B.V.)