Systematic Reveiws
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 18, 2017; 9(14): 677-688
Published online May 18, 2017. doi: 10.4254/wjh.v9.i14.677
Inducible protein-10 as a predictive marker of antiviral hepatitis C treatment: A systematic review
Bastian Neesgaard, Morten Ruhwald, Nina Weis
Bastian Neesgaard, Nina Weis, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark
Morten Ruhwald, Department of Infectious Disease Immunology, Section of Human Immunology, Statens Serum Institute, 2300 Copenhagen S, Denmark
Nina Weis, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen Ø, Denmark
Author contributions: Neesgaard B and Weis N contributed equally to this work; Neesgaard B and Weis N designed the research; Neesgaard B and Weis N performed the research; Neesgaard B, Ruhwald M and Weis N analyzed the data; Neesgaard B and Weis N wrote the paper.
Supported by Amagar and Hvidovre Hospital Research Foundation of 45000 Dkr. (to Bastian Neesgaard); and The Family Hede Nielsen Foundation of 10000 Dkr. (to Bastian Neesgaard).
Conflict-of-interest statement: Ruhwald M is registered as inventor on a patent application disclosing IP-10 based liver fibrosis monitoring, using DBS, which could be viewed as a conflict-of-interest. Otherwise all the authors declare that they have no competing interests.
Data sharing statement: The technical appendix, and dataset are available from the corresponding author at
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Nina Weis, MD, PhD, Associate Professor, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre, Kettegårds allé 30, 2650 Hvidovre, Denmark.
Telephone: +45-38-623514 Fax: +45-38-623504
Received: October 22, 2016
Peer-review started: October 28, 2016
First decision: December 1, 2016
Revised: December 30, 2016
Accepted: January 16, 2017
Article in press: January 18, 2017
Published online: May 18, 2017

To investigate interferon-γ-inducible protein-10’s (IP-10) potential to anticipate rapid (RVR)- and sustained virological responses (SVR) to chronic hepatitis C (CHC) treatment.


We included case series examining RVR or SVR in relation to 24 or 48 wk treatment for CHC, in patients treatment free for at least six months, with genotype 1 or 4, and in relation to 24 wk treatment for genotype 2 and 3, with pegylated interferon in combination with ribavirin. Patients had to have both a baseline IP-10 level as well as a hepatitis C virus (HCV)-RNA determination 4 wk after treatment initiation or 24 wk after end of treatment. Studies including patients with liver diseases other than CHC, human immunodeficiency virus-infection, treatment with immunosuppresents or cytostatica, alcohol dependency or active intravenous drug-use were excluded. We found 81 articles by searching the MEDLINE and EMBASE databases. Eight studies were eligible for inclusion. Their quality were assesed using an 18 point checklist for case series, developed using a modified Delphi technique. Information was extracted from the articles, and no raw data was requisitioned. The review protocol was registered at the International Prospective Register of Systematic Reviews (reg. number: CRD42014008736).


Three studies reported on baseline IP-10 level in association with RVR. A signigficant association was found for HCV genotype 1 infection by two studies. Only two studies reported on HCV genotype 4 infected and genotype 2 and 3 infected patients, respectively. A trend was seen for an association between RVR and baseline IP-10 for genotype 4, while no association was found for genotype 2 and 3. Seven studies provided information regarding baseline IP-10 and SVR. Following the pattern regarding rapid virological response all five studies examining SVR in relation to baseline IP-10 levels for HCV, genotype 1 infected patients showed a significant association. Likewise a significant association was seen for HCV, genotype 4 infected, while no association was found for HCV, genotype 2 and 3 infected. Though only two studies examined the assosiation for HCV genotype 4 infected and HCV genotype 2 and 3 infected respectively.


We found indications of a possible association between baseline IP-10 level and virological responses in patients with CHC genotype 1 and 4.

Keywords: Chronic hepatitis C, Inducible protein-10’s, Sustained virological response, Interferon-γ-inducible protein-10, CXCL-10, Chemokine, Genotype, Pegylated interferon, Ribavirin, Rapid virological response

Core tip: This is the first systematic review examining the association between baseline levels of interferon-γ-inducible protein-10 (IP-10) and virological response to treatment with pegylated interferon and ribavirin among patients chronically infected with hepatitis C virus, genotype 1-4. We found a possible correlation for genotype 1 and 4 infected patients, indicating that baseline IP-10 levels could predict which patients, infected with genotype 1 or 4, would have the highest likelihood of benefitting from antiviral treatment with pegylated interferon and ribavirin. These findings can be especially relevant in countries, where treatments with direct acting antivirals are not readily applicable.