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Impact of hepatitis C virus core mutations on the response to interferon-based treatment in chronic hepatitis C

World Journal of Gastroenterology 2016年第37期22卷 8406-8413页

作者： camelia sultana Gabriela Oprisan Monica Delia Teleman Sorin Dinu HepGen 88/2012 Project Team Cristiana Oprea Mihai Voiculescu Simona Ruta Virology Discipline Carol Davila University of Medicine and Pharmacy Emergent Diseases Department Stefan S.Nicolau Institute of Virology Faculty of Pharmacy Titu Maiorescu University Molecular Epidemiology Laboratory NIRDMI Cantacuzino Department of Microbiology and Epidemiology Carol Davila University of Medicine and Pharmacy Victor Babes Clinic of Infectious and Tropical Diseases Fundeni Institute

AIM To determine whether hepatitis C virus(HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients. METHODS One hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein(Big Dye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28 B gene rs12979860(Custom TaqM an 5' allelic discrimination assay; Applied Biosystems).RESULTS Of the patients, all were infected with HCV genotype 1b, 44.4% had low baseline HCV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response(SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70(R70Q/H) or/and position 91(L91M). The favorable IL28 B CC polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age(P < 0.001), urban residence(P = 0.004), IL28 B CC genotype(P < 0.001), absence of core mutations(P = 0.005), achievement of rapid virologic response(P < 0.001) and early virological response(P < 0.001) were significantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age(P < 0.001), absence of core substitutions(P = 0.04) and IL28 B CC genotype(P < 0.001); the model correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%. CONCLUSION HCV core mutations can help distinguish between patients who can still benefit from the affordable IFNbased therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease.

关键词： Chronic hepatitis C Caucasian patients Core substitutions IL28B polymorphism Treatment

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