IL-28B Polymorphisms and the Response to Antiviral Therapy in HCV Genotype 2 and 3 Varies by Ethnicity

A Meta-Analysis

A. S. Rangnekar; R. J. Fontana

Disclosures

J Viral Hepat. 2013;20(6):377-384. 

In This Article

Abstract and Introduction

Abstract

Studies of IL-28B genotype in patients with hepatitis C virus (HCV) genotype 2/3 infection have yielded conflicting results. The aim of this meta-analysis was to obtain a pooled odds ratio (OR) of the impact of IL-28B genotype on achieving sustained virologic response (SVR) in patients with HCV genotype 2/3 infection treated with pegIFN and ribavirin. A meta-analysis with a random effects model was performed, and study heterogeneity and publication bias were assessed. Forty-three percent of the Caucasians (11 studies) and 86% of Asians (five studies) had the favourable IL-28B genotype. In Caucasians, the pooled OR of SVR with the favourable IL-28B genotype was 1.36 (95%CI: 0.98–1.88, P = 0.07) in all patients and 1.55 (95%CI: 1.10–2.18, P = 0.01) in patients treated with pegIFN and ribavirin for ≥24 weeks. In Asians, the pooled OR of SVR in patients with the favourable IL-28B genotype was 1.99 (95%CI: 0.94–4.25, P = 0.07). The favourable IL-28B genotype was also significantly associated with rapid virologic response (RVR) in both groups (Caucasians: OR: 1.82, 95%CI: 1.12–2.96, P = 0.02; Asians: 2.39, 95%CI: 1.39–4.11, P = 0.002), as well as the likelihood of an SVR in a subgroup of 350 Caucasian patients without an RVR (OR: 3.29, 95%CI: 1.67–6.51, P = 0.001). The favourable IL-28B genotype is a statistically significant predictor of SVR and RVR in Caucasian patients treated with pegIFN and ribavirin for 24 weeks. In contrast, the favourable IL-28B genotype is associated with RVR, but not SVR in Asian HCV genotype 2 patients.

Introduction

A single nucleotide polymorphism (SNP) upstream of the interleukin 28B (IL-28B) gene is associated with hepatic responsiveness to interferon therapy in hepatitis C virus (HCV) genotype 1 patients.[1] The highly variable prevalence of the favourable IL-28B genotype in patients of varying ethnicity, in part, explains differences in the observed sustained virologic response (SVR) rates. Although other host, viral and treatment factors may influence a patient's chance of SVR, the favourable IL-28B genotype is the single most important pretreatment predictor of achieving SVR with peginterferon (pegIFN) and ribavirin therapy in genotype 1 patients.[2] In contrast, the association of IL-28B and SVR in patients with HCV genotype 2/3 infection remains unclear.[3–5]

Although patients with HCV genotype 2/3 are more responsive to pegIFN and ribavirin, up to 30% of treated patients will not achieve SVR.[6] Furthermore, the new direct acting antiviral agents (DAAs), boceprevir and telaprevir, are not approved for the use in patients with HCV genotype 2/3 infection.[7] As such, pegIFN and ribavirin remain the only currently approved treatment for these patients. This meta-analysis was undertaken to better quantify the effect of the favourable IL-28B genotype on achieving SVR after treatment with pegIFN and ribavirin in patients with chronic HCV genotype 2/3 infection. In addition, the effect of IL-28B on achieving a week 4 rapid virologic response (RVR) as well as the impact of patient ethnicity on SVR was evaluated.

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