Hepatitis C: viral and host factors associated with non-response to pegylated interferon plus ribavirin

Liver International
Early View (Articles online in advance of print)
Published Online: 14 Jul 2010
© 2010 John Wiley & Sons A/S

Tarik Asselah 1,2 , Emilie Estrabaud 1 , Ivan Bieche 3,4 , Martine Lapalus 1 , Simon De Muynck 1 , Michel Vidaud 3,4 , David Saadoun 5 , Vassili Soumelis 6 and Patrick Marcellin 1,2

1 INSERM, U773, Centre de Recherche Bichat-Beaujon CRB3, Paris, France
2 Service d'hépatologie, Hôpital Beaujon, Clichy, France
3 INSERM, U745, Université René Descartes, Paris, France
4 Service de Biochimie, Hôpital Beaujon, Clichy, France
5 Service de Médecine Interne, Hôpital Pitié-Salpétrière, Paris, France
6 INSERM U653, Institut Curie, Paris, France

Correspondence
Dr Tarik Asselah, Service d'Hépatologie, Hôpital Beaujon, 100 Bd du Gl Leclerc, 92110 Clichy, France
Tel: +33 1 4087 5579
Fax: +33 1 4730 9440
e-mail: tarik.asselah@bjn.aphp.fr

Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://www3.interscience.wiley.com/authorresources/onlineopen.html

KEYWORDS

antiviral • boceprevir • immunity • interferon-stimulated genes • pegylated-interferon • polymerase inhibitors • protease inhibitors • STAT-C • sustained virological response • telaprevir

ABSTRACT

Treatment for chronic hepatitis C virus (HCV) infection has evolved considerably in the last years. The standard of care (SOC) for HCV infection consists in the combination of pegylated interferon (PEG-IFN) plus ribavirin. However, it only induces a sustained virological response (SVR) in half of genotype 1-infected patients. Several viral and host factors have been associated with non-response: steatosis, obesity, insulin resistance, age, male sex, ethnicity and genotypes. Many studies have demonstrated that in non-responders, some interferon-stimulated genes were upregulated before treatment. Those findings associated to clinical, biochemical and histological data may help detect responders before starting any treatment. This is a very important issue because the standard treatment is physically and economically demanding. The future of HCV treatment would probably consist in the addition of specifically targeted antiviral therapy for HCV such as protease and/or polymerase inhibitors to the SOC. In genotype 1 patients, very promising results have been reported when the protease inhibitor telaprevir or boceprevir is added to the SOC. It increases the SVR rates from approximately 50% (PEG-IFN plus ribavirin) to 70% (for patients treated with a combination of PEG-IFN plus ribavirin plus telaprevir). Different elements are associated with non-response: (i) viral factors, (ii) host factors and (iii) molecular mechanisms induced by HCV proteins to inhibit the IFN signalling pathway. The goal of this review is to present the mechanisms of non-response, to overcome it and to identify factors that can help to predict the response to anti-HCV therapy.

Received 24 August 2009
Accepted 30 April 2010
DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1478-3231.2010.02283.x About DOI
 
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