Who Is More Likely to Respond to Dual Treatment With Pegylated-Interferon and Ribavirin for Chronic Hepatitis C?

A Gender-Oriented Analysis

V. Di Marco; L. Covolo; V. Calvaruso; M. Levrero; M. Puoti; F. Suter; G. B. Gaeta; C. Ferrari; G. Raimondo; G. Fattovich; T. Santantonio; A. Alberti; R. Bruno; C. Mussini; M. Mondelli; F. Donato; A. Craxì

Disclosures

J Viral Hepat. 2013;20(11):790-800. 

In This Article

Abstract and Introduction

Abstract

We assessed, in real-life practice, viral, demographic, genetic and metabolic factors influencing the sustained virologic response (SVR), with a gender-oriented analysis, in patients with chronic hepatitis C virus (HCV) treated with pegylated interferon and ribavirin. Six hundred and seventy naïve patients were treated with dual therapy and evaluated by gender and HCV genotype. Associations between baseline variables and SVR were assessed by multivariate logistic regression analysis. Among 362 genotype 1 patients, SVR was achieved in 158 patients (44%), and SVR was independently associated with age less than 50 years (OR 2.12; 95% CI 1.09–4.30; P = 0.039) and C/C genotype rs12979860 SNP (OR 2.83; 1.19–6.74; P = 0.002) in 163 females, while absence of visceral obesity (OR 2.491; 1.131–5.487; P = 0.023), HCV-RNA lower than 400 000 IU/mL (OR 2.66; 1.273–5.558; P = 0.009) and C/C genotype rs12979860 SNP (OR 4.969; 2.401–10.283; P < 0.001) were independently associated with SVR in 199 males. Combining favourable baseline variables, the probability of obtaining SVR ranged from 27.6% to 84.2% in females, and from 14.3% to 85.7% in males. The rate of SVR was 81.1% in 175 genotype 2 patients, and 69% in 100 genotype 3 patients. Rapid virologic response was the only valid predictor of SVR regardless of other features. In conclusions, in the setting of HCV genotype 1, chronic hepatitis, combining rapid virologic response and predictive factors, which are different for females and males, allows clinicians to single out a group of patients whose likelihood of SVR exceeds 80%. For these patients, triple therapy with first-generation protease inhibitors may be unwarranted.

Introduction

Antiviral treatment reduces the rate of progression of chronic hepatitis C towards cirrhosis and HCC.[1–4] Dual therapy (DT) with pegylated interferon (Peg-IFN) and ribavirin (RBV) achieves a sustained virologic response (SVR) in more than 75% of naive patients infected by genotypes 2 or 3, and in about 45% of naive patients with genotypes 1 or 4.[5–8] The addition of first-generation hepatitis C virus (HCV) protease inhibitors (boceprevir or telaprevir) to DT leads to a substantial improvement in SVR rates, with the option of abbreviated therapy in naïve patients with genotype 1.[9,10] In the light of the results of pivotal trials, the American Association for the Study of Liver Disease (AASLD) recommended the universal use of boceprevir or telaprevir in combination with Peg-IFN and RBV as the optimal therapy for genotype 1 naïve patients.[11]

Various viral factors, as well as genetic, metabolic and immunological characteristics of patients have been found to influence the response to IFN-based therapy. The single most important viral factor influencing the response to antiviral treatment is HCV genotype.[5–7] Among genetic factors, single-nucleotide polymorphisms (SNPs) located in and near the interleukin 28B (IL28B) locus, which encodes for IFN-λ3, are associated with a higher rate of SVR in genotype 1 patients treated with Peg-IFN and RBV.[12–15] The role of metabolic factors, such as overweight and visceral obesity, steatosis, insulin resistance and diabetes, in contrasting the response to antiviral therapy has been investigated widely in the last decade.[12–24] Recent studies suggest that in genotype 1 females, menopause is associated with an increased severity of liver fibrosis, and with a low likelihood of response to therapy with Peg-IFN and RBV.[25,26] Finally, baseline serum HCV-RNA levels and the rapid disappearance of serum HCV-RNA during the first 4 weeks of treatment can influence the rate of SVR.[27,28]

The aim of this large clinical practice study was to make a comprehensive assessment, with a gender-oriented model of analysis, of the role of viral and host factors which may influence the rate of SVR to determine whether some patients have such a high a likelihood of response to dual therapy that they should avoid the use of first-generation protease inhibitors, with their attendant adverse effects and high costs.

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