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Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C.

Journal article
Authors Galia Askarieh
Åsa Alsiö
Paolo Pugnale
Francesco Negro
Carlo Ferrari
Avidan U Neumann
Jean-Michel Pawlotsky
Solko W Schalm
Stefan Zeuzem
Gunnar Norkrans
Johan Westin
Jonas Söderholm
Kristoffer Hellstrand
Martin Lagging
Published in Hepatology
Volume 51
Issue 5
Pages 1523-1530
ISSN 1527-3350
Publication year 2010
Published at Institute of Biomedicine, Department of Infectious Medicine
Pages 1523-1530
Language en
Links dx.doi.org/10.1002/hep.23509
Keywords Adult, Chemokine CXCL10, blood, metabolism, Drug Therapy, Combination, Female, Hepacivirus, genetics, Hepatitis C, Chronic, drug therapy, genetics, Humans, Interferon Alfa-2a, administration & dosage, therapeutic use, Liver, metabolism, Male, Middle Aged, Polyethylene Glycols, administration & dosage, therapeutic use, Prognosis, RNA, Viral, genetics, metabolism, Ribavirin, administration & dosage, therapeutic use
Subject categories Microbiology in the medical area

Abstract

High systemic levels of interferon-gamma-inducible protein 10 kDa (IP-10) at onset of combination therapy for chronic hepatitis C virus (HCV) infection predict poor outcome, but details regarding the impact of IP-10 on the reduction of HCV RNA during therapy remain unclear. In the present study, we correlated pretreatment levels of IP-10 in liver biopsies (n = 73) and plasma (n = 265) with HCV RNA throughout therapy within a phase III treatment trial (DITTO-HCV). Low levels of plasma or intrahepatic IP-10 were strongly associated with a pronounced reduction of HCV RNA during the first 24 hours of treatment in all patients (P < 0.0001 and P = 0.002, respectively) as well as when patients were grouped as genotype 1 or 4 (P = 0.0008 and P = 0.01) and 2 or 3 (P = 0.002, and P = 0.02). Low plasma levels of IP-10 also were predictive of the absolute reduction of HCV RNA (P < 0.0001) and the maximum reduction of HCV RNA in the first 4 days of treatment (P < 0.0001) as well as sustained virological response (genotype 1/4; P < 0.0001). To corroborate the relationship between early viral decline and IP-10, pretreatment plasma samples from an independent phase IV trial for HCV genotypes 2/3 (NORDynamIC trial; n = 382) were analyzed. The results confirmed an association between IP-10 and the immediate reduction of HCV RNA in response to therapy (P = 0.006). In contrast, pretreatment levels of IP-10 in liver or in plasma did not affect the decline of HCV RNA between days 8 and 29, i.e., the second-phase decline, or later time points in any of these cohorts. CONCLUSION: In patients with chronic hepatitis C, low levels of intrahepatic and systemic IP-10 predict a favorable first-phase decline of HCV RNA during therapy with pegylated interferon and ribavirin for genotypes of HCV.

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