• Home
  1. Home
  2. 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
Scientific article
English

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

Contributors

Askarieh, Galia; Alsio, Asa; Pugnale, Paolo; Negro, Francesco; Ferrari, Carlo; Neumann, Avidan U.; Pawlotsky, Jean-Michel; Schalm, Solko W.; Zeuzem, Stefan; Norkrans, Gunnar; Westin, Johan; Soderholm, Jonas; Hellstrand, Kristoffer; Lagging, Martin

Published in

Hepatology, vol. 51, no. 5, p. 1523-1530

Publication date

2010

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.

Keywords

  • Adult
  • Chemokine CXCL10/blood/*metabolism
  • Drug Therapy, Combination
  • Female
  • Hepacivirus/genetics
  • Hepatitis C, Chronic/drug therapy/*genetics
  • Humans
  • Interferon-alpha/administration & dosage/therapeutic use
  • Liver/metabolism
  • Male
  • Middle Aged
  • Polyethylene Glycols/administration & dosage/therapeutic use
  • Prognosis
  • RNA, Viral/*genetics/metabolism
  • Recombinant Proteins
  • Ribavirin/administration & dosage/therapeutic use

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

ASKARIEH, Galia et al. 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. In: Hepatology, 2010, vol. 51, n° 5, p. 1523–1530. doi: 10.1002/hep.23509

Main files (1)

Article

Identifiers

Additional URL for this publication

http://onlinelibrary.wiley.com/store/10.1002/hep.23509/asset/23509_ftp.pdf?v=1&t=h1qf1ryb&s=53c3554bfbdc2cde2a702933d9fa53c685fb435c

Journal ISSN

0270-9139
571views
0downloads

Technical informations

Creation

23/05/2012 08:44:04

First validation

23/05/2012 08:44:04

Update

14/03/2023 17:31:32

Status update

14/03/2023 17:31:31

Last indexation

29/10/2024 19:55:12
All rights reserved by Archive ouverte UNIGE and the University of Geneva
OpenAIRE Indexed & Validated