Influence of Ribavirin Serum Levels on Outcome of Antiviral Treatment and Anemia in Hepatitis C Virus Infection.

Thomas Kuntzen,Andreas Geier,Sereina Kuhn,Burkhardt Seifert,Daniela Kuntzen,Beat Müllhaupt,Golo Ahlenstiel

doi:10.1371/journal.pone.0158512

Abstract

BackgroundRibavirin blood levels vary considerably between patients with standard weight-based dosing. Their impact on sustained virological response (SVR) with pegylated interferon and ribavirin is controversial, but has mostly been studied before the IL28b gene polymorphism as a possible confounder was discovered.MethodsThe impact of serum ribavirin trough levels at week 4, at the end of treatment and of mean levels across the entire antiviral treatment with pegylated interferon and ribavirin on relapse, SVR rates and anemia was retrospectively studied by univariate and multivariable logistic regression analyses in 214 patients with HCV genotype 1–4 infection, including 88 patients with available IL28b genotyping.ResultsMean ribavirin levels varied between 0.68–5.65 mg/l and significantly differed between patients with or without SVR. By multivariable regression including age, sex, HCV viral load, HCV genotype, liver fibrosis stage, prior treatments, immunosuppression and IL28b genotype, ribavirin levels consistently displayed significant influence on SVR and relapse without indication for a specific importance of higher concentrations early or late in the treatment course. Although hemoglobin decline was on average more pronounced in patients with higher ribavirin levels, hemoglobin remained relatively stable in a significant proportion of these, indicating that ribavirin levels alone are insufficient to predict anemia.ConclusionWhile data are scarce to draw conclusions applicable for modern DAA therapies, these results support ribavirin treatment based on serum levels instead of purely weight-based dosing in combination with pegylated interferon.

Highlights

Pegylated interferon and ribavirin have been the standard treatment for Hepatitis C virus (HCV) infection for more than a decade and are still in use in many developing countries
The impact of serum ribavirin trough levels at week 4, at the end of treatment and of mean levels across the entire antiviral treatment with pegylated interferon and ribavirin on relapse, sustained virological response (SVR) rates and anemia was retrospectively studied by univariate and multivariable logistic regression analyses in 214 patients with HCV genotype 1–4 infection, including 88 patients with available IL28b genotyping
Mean ribavirin levels varied between 0.68–5.65 mg/l and significantly differed between patients with or without SVR

Summary

Introduction

Pegylated interferon and ribavirin have been the standard treatment for Hepatitis C virus (HCV) infection for more than a decade and are still in use in many developing countries. Ribavirin plasma levels vary considerably between patients even with weight-based dosing [8]. Each study focused on special patient subgroups, ribavirin dosing strategies or sample time points [11,12,13,14,15] It is still unclear whether ribavirin concentrations might be relevant and could warrant therapeutic drug monitoring in anti-HCV treatment. Ribavirin blood levels vary considerably between patients with standard weight-based dosing. Their impact on sustained virological response (SVR) with pegylated interferon and ribavirin is controversial, but has mostly been studied before the IL28b gene polymorphism as a possible confounder was discovered

Methods

Results

Conclusion