Female Sex and IL28B, a Synergism for Spontaneous Viral Clearance in Hepatitis C Virus (HCV) Seroconverters from a Community-Based Cohort

Charlotte H B S Van Den Berg,Maria Prins,Roel A Coutinho,Debbie Van Baarle,Richard Molenkamp,Thijs Van De Laar,Janke Schinkel,Bart P X Grady,Robin Van Houdt,Rick Edward Paul

doi:10.1371/journal.pone.0027555

Abstract

Background & AimsSince acute hepatitis C virus (HCV) infection is often asymptomatic, it is difficult to examine the rate and determinants of spontaneous clearance. Consequently, these studies are subject to bias, which can potentially lead to biased rates of viral clearance and risk estimates. We evaluated determinants of spontaneous HCV clearance among HCV seroconverters identified in a unique community-based cohort.MethodsSubjects were 106 drug users with documented dates of HCV seroconversion from the Amsterdam Cohort Study. Logistic regression was used to examine sociodemographic, behavioral, clinical, viral and host determinants, measured around acute infection, of HCV clearance.ResultsThe spontaneous viral clearance rate was 33.0% (95% confidence interval (CI) 24.2–42.8). In univariate analyses female sex and fever were significantly associated with spontaneous clearance. The favorable genotypes for rs12979860 (CC) and rs8099917 (TT) were associated with spontaneous clearance, although borderline significant. In multivariate analysis, females with the favorable genotype for rs12979860 (CC) had an increased odds to spontaneously clear HCV infection (adjustedOR 6.62, 95% 2.69–26.13), whereas females with the unfavorable genotype were as likely as men with the favorable and unfavorable genotype to clear HCV. Chronic Hepatitis B infection and absence of HIV coinfection around HCV seroconversion also favor HCV clearance.ConclusionsThis study shows that co-infection with HIV and HBV and genetic variation in the IL28B region play an important role in spontaneous clearance of HCV. Our findings suggest a possible synergistic interaction between female sex and IL28B in spontaneous clearance of HCV.

Highlights

Hepatitis C virus (HCV) is mainly transmitted through exposure to infected blood [1]
Treatment success rates are higher when individuals are treated during acute hepatitis C virus (HCV) than when they are treated during chronic infection [5,6,7]
The limited published data indicated that 14–42% of persons with acute HCV cleared the virus, and that clearance is associated with symptomatic acute HCV, female sex, non-black race, lower peak HCV-RNA titer, induction of neutralizing antibodies early in HCV infection, and high and broad HCV-specific CD4+ and CD8+ T-cell responses [7,9,10,11,12,13,14,15,16,17]

Summary

Introduction

Hepatitis C virus (HCV) is mainly transmitted through exposure to infected blood [1]. The majority of the studies on spontaneous viral clearance have been conducted among anti-HCV positive individuals, for whom the exact moment of anti-HCV seroconversion is unknown. These prevalence studies are subject to selection bias, which can potentially lead to biased rates of viral clearance and risk estimates [8]. Since acute hepatitis C virus (HCV) infection is often asymptomatic, it is difficult to examine the rate and determinants of spontaneous clearance. These studies are subject to bias, which can potentially lead to biased rates of viral clearance and risk estimates. We evaluated determinants of spontaneous HCV clearance among HCV seroconverters identified in a unique community-based cohort

Methods

Results

Conclusion