Plasma interferon-gamma-inducible protein-10 (IP-10) levels during acute hepatitis C virus infection*

Authors


  • Potential conflict of interest: J.G. is a consultant/advisor for Merck. G.D. is a consultant/advisor and has received research grants from Roche, Merck, Janssen, Gilead, Bristol Myers Squibb.

  • Funded by the National Institutes of Health grant RO1 DA 15999-01. The Kirby Institute for Infection and Immunity in Society is funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. The HEPCO Cohort is supported by grants from the Canadian Institutes for Health Research (CIHR) (MOP-106468 and HEO-115696) and Fonds de recherche du Québec – Santé (FRQS) AIDS and Infectious Disease Network (Réseau SIDA-MI). Roche Pharmaceuticals supplied financial support for pegylated IFN-alfa-2a/ribavirin. J.G. is supported by a National Health and Medical Research Council Career Development Fellowship. G.D. and A.L. were supported by National Health and Medical Research Council Practitioner Research Fellowships. M.H. and J.K. were supported by National Health and Medical Research Council Research Fellowships. N.H.S. and J.B. hold Chercheur Boursier salary awards from the FRQS. The Burnet Institute receives funding support from the Victorian Operational Infrastructure Support Program, Department of Health, Victoria, Australia.

Abstract

Systemic levels of interferon-gamma-inducible protein-10 (IP-10) are predictive of treatment-induced clearance in chronic hepatitis C virus (HCV). In the present study, factors associated with plasma IP-10 levels at the time of acute HCV detection and the association between IP-10 levels and spontaneous clearance were assessed in three cohorts of acute HCV infection. Among 299 individuals, 245 (181 male, 47 human immunodeficiency virus-positive [HIV+]) were HCV RNA+ at acute HCV detection. In adjusted analysis, factors independently associated with IP-10 levels ≥150 pg/mL (median level) included HCV RNA levels >6 log IU/mL, HIV coinfection and non-Aboriginal ethnicity. Among 245 HCV RNA+ at acute HCV detection, 214 were untreated (n = 137) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n = 77). Spontaneous clearance occurred in 14% (29 of 214). Individuals without spontaneous clearance had significantly higher mean plasma IP-10 levels at the time of acute HCV detection than those with clearance (248 ± 32 versus 142 ± 22 pg/mL, P = 0.008). The proportion of individuals with spontaneous clearance was 0% (0 of 22, P = 0.048) and 16% (27 of 165) and in those with and without plasma IP-10 levels ≥380 pg/mL. In adjusted analyses, favorable IL28B genotype was associated with spontaneous clearance, while higher HCV RNA level was independently associated with lower odds of spontaneous clearance. Conclusion: High IP-10 levels at acute HCV detection were associated with failure to spontaneously clear HCV. Patients with acute HCV and high baseline IP-10 levels, particularly >380 pg/mL, should be considered for early therapeutic intervention, and those with low levels should defer therapy for potential spontaneous clearance. (HEPATOLOGY 2013;)

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