A Predictive Model for Selecting Patients with HCV Genotype 3 Chronic Infection with a High Probability of Sustained Virological Response to Peginterferon Alfa-2a/Ribavirin.

Tarik Asselah,Alex J Thompson,Georgios Bakalos,Diethelm Messinger,Robert Flisiak,Manuel Romero-Gomez,Mitchell L Shiffman,Chen-Hua Liu

doi:10.1371/journal.pone.0150569

Abstract

BackgroundAccess to direct-acting antiviral agents (DAAs) is restricted in some settings; thus, the European Association for the Study of the Liver recommends dual peginterferon/ribavirin (PegIFN/RBV) therapy wherever DAAs are unavailable. HCV genotype (GT) 3 infection is now the most difficult genotype to eradicate and PegIFN/RBV remains an effective option. The goal of this study was to devise a simple predictive score to identify GT3 patients with a high probability of achieving a sustained virologic response (SVR) with PegIFN alfa-2a/RBV therapy.MethodsRelationships between baseline characteristics and SVR were explored by multiple logistic regression models and used to develop a simple scoring system to predict SVR using data from 1239 treatment-naive GT3 patients who received PegIFN alfa-2a/RBV for 24 weeks in two large observational cohort studies.ResultsThe score was validated using a database of 473 patients. Scores were assigned for six factors as follows: age (years) (≤40: 2 points; >40 but ≤55: 1); bodyweight (kg) (<70: 2; ≥70 but <90: 1); no cirrhosis/transition to cirrhosis (2); ALT ≤2.5 x ULN (1); platelets (109/L) (>200: 2; ≥100 but <200: 1); HCV RNA (<400,000 IU/mL: 1). The points are summed to arrive at a score ranging from 0‒10 where higher scores indicate higher chances of SVR; 141, 123, 203, 249, 232, and 218 patients had total scores of 0‒4, 5, 6, 7, 8, and 9–10, respectively, among whom SVR rates were 45%, 62%, 72%, 76%, 84%, and 89%. Among 622 patients who had scores of 6‒10 and HCV RNA <50 IU/mL by treatment week 4 the SVR rate was 86% (532/622).ConclusionsA simple baseline scoring system involving age, bodyweight, cirrhosis status, ALT level, platelet count and HCV RNA level can be used to identify treatment-naive Caucasian patients with HCV GT3 infection with a high probability of SVR with PegIFN alfa-2a/RBV therapy.

Highlights

Hepatitis C virus (HCV) is a major cause of chronic liver disease, with more than 185 million people infected worldwide [1,2,3]
Relationships between baseline characteristics and sustained virologic response (SVR) were explored by multiple logistic regression models and used to develop a simple scoring system to predict SVR using data from 1239 treatment-naive GT3 patients who received PegIFN alfa-2a/RBV for 24 weeks in two large observational cohort studies
Scores were assigned for six factors as follows: age (40: 2 points; >40 but 55: 1); bodyweight (

Summary

Introduction

Hepatitis C virus (HCV) is a major cause of chronic liver disease, with more than 185 million people infected worldwide [1,2,3]. According to guidelines issued by the European Association for the Study of the Liver (EASL), three regimens are recommended for the treatment of patients infected with HCV GT3, namely the combination of sofosbuvir plus peginterferon alfa (PegIFN)/ribavirin (RBV), the interferon-free combination of sofosbuvir plus ribavirin, or the interferon-free combination of sofosbuvir plus daclatasvir [8]. The majority of HCV infected patients worldwide have not yet been treated;[12] treatment experienced patients represent an area of high unmet medical need with the EASL guidelines recommending they receive either sofosbuvir plus PegIFN)/RBV or sofosbuvir plus daclatasvir [8]. The goal of this study was to devise a simple predictive score to identify GT3 patients with a high probability of achieving a sustained virologic response (SVR) with PegIFN alfa-2a/RBV therapy

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