Abstract

BackgroundHigh plasma levels of interferon-gamma inducible protein-10 (IP-10) have been shown to be associated with impaired treatment response in chronic hepatitis C virus (HCV) infection. Whether IP-10 levels predict treatment in acute HCV infection is unknown.MethodsPatients with acute or early chronic HCV infection from the Australian Trial in Acute Hepatitis C (ATAHC) cohort were evaluated. Baseline and on-treatment plasma IP-10 levels were measured by ELISA. IL28B genotype was determined by sequencing.ResultsOverall, 74 HCV mono-infected and 35 HIV/HCV co-infected patients were treated in ATAHC, of whom 89 were adherent to therapy and were included for analysis. IP-10 levels correlated with HCV RNA levels at baseline (r = 0.48, P<0.001) and during treatment. Baseline IP-10 levels were higher in patients who failed to achieve rapid virological response (RVR). Only one patient with a plasma IP-10 level >600 pg/mL achieved RVR. There was no association with IP-10 levels and early virological response (EVR) or sustained virological response (SVR).ConclusionsBaseline IP-10 levels are associated with early viral kinetics but not ultimate treatment outcome in acute HCV infection. Given previous data showing that patients with high baseline IP-10 are unlikely to spontaneously clear acute HCV infection, they should be prioritized for early antiviral therapy.

Highlights

  • The development of direct-acting antivirals (DAAs) has markedly improved response rates for chronic hepatitis C virus (HCV) infection

  • inducible protein-10 (IP-10) levels correlated with HCV RNA titre (p,0.0001, r = 0.42) (Figure 1) and mean baseline IP-10 levels were higher in those with HCV RNA above 400,000 IU/ mL (5226110 vs. 246642 pg/mL, P = 0.012) (Figure 2a)

  • Mean IP-10 levels were higher in patients with the treatment unfavorable IL28B genotype at rs8099917

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Summary

Introduction

The development of direct-acting antivirals (DAAs) has markedly improved response rates for chronic hepatitis C virus (HCV) infection. Treatment during the acute phase of HCV infection is associated with excellent treatment outcomes with interferon-based therapy without DAAs [1]. In the initial study of interferon treatment for acute HCV, Jaeckel and colleagues found a striking 98% rate of SVR [2]. Many subsequent studies have shown good outcomes with peginterferon therapy with or without ribavirin in acute HCV infection [3]. High plasma levels of interferon-gamma inducible protein-10 (IP-10) have been shown to be associated with impaired treatment response in chronic hepatitis C virus (HCV) infection. Whether IP-10 levels predict treatment in acute HCV infection is unknown

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