Current status and emerging challenges in the treatment of hepatitis C virus genotypes 4 to 6

Abstract

Hepatitis C virus (HCV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endpoints. Response rates to a 48-wk combined peginterferon/ribavirin treatment range to 40%-69% for HCV 4, 55%-60% for HCV 5 and 60%-90% for HCV 6. Response-guided schedules are recommended to optimize the outcomes of peginterferon/ribavirin treatment in HCV 4 and, in form of preliminary data, for HCV 6, but no data are yet available to support such an individualization of therapy for HCV 5. Recently, the direct-acting antivirals (DAAs) with pan-genotypic activities simeprevir, sofosbuvir and daclatasvir have been recommended in triple regimens with peginterferon/ribavirin for the treatment of HCV genotypes 4 to 6 infections. In the future, DAA-based interferon-free therapies are awaited to drastically improve treatment outcomes in HCV. However, efforts to improve treatment outcomes with peginterferon/ribavirin should continue, as the HCV 4-6 infected population is mainly based in resource-limited settings with restricted access to the costly DAAs.

Keywords: Direct-acting antivirals; Genotype 4; Genotype 5; Genotype 6; Hepatitis C virus; Pegylated interferon; Ribavirin.

Figures

Figure 1

Prospective studies evaluating a fixed 48-wk treatment using a standard dose of pegylated interferon and ribavirin in patients with hepatitis C genotype 4. SVR: Sustained viral response.

Figure 2

Studies comparing outcomes of 24 vs 48 wk of therapy with pegylated interferon and ribavirin in patients with hepatitis C virus genotype 6. aTreatment duration was tailored according to viral response at week 4: Patients with negative hepatitis C virus-RNA received 24 wk of treatment; the remainder received 48 wk. ns: Non-significant; nr: Not reported.