European Journal of Clinical Investigation
Early View (Articles online in advance of print)
Published Online: 6 Jul 2010
Journal Compilation © 2010 Stichting European Society for Clinical Investigation Journal Foundation
Andri Rauch * , Janine Rohrbach * and Pierre-Yves Bochud †
* University Clinic of Infectious Diseases, University Hospital Bern and University of Bern, Bern , † Department of Medicine, Service of Infectious Diseases, Institute of Microbiology, University Hospital and University of Lausanne, Switzerland
Correspondence to Andri Rauch, MD, University Clinic of Infectious Diseases, Inselspital PKT2B, 3010 Bern – Switzerland. Tel.: +41 31 632 15 74; fax: +41 31 632 31 76; e-mail: email@example.com
Copyright Journal Compilation © 2010 Stichting European Society for Clinical Investigation Journal Foundation
Hepatitis C treatment • hepatitis C virus • host genomics • interleukin 28B • spontaneous clearance
Eur J Clin Invest 2010
Background Hepatitis C Virus (HCV) infection is spontaneously resolved in about 30% of acutely infected individuals. In those who progress to chronic hepatitis C, HCV therapy permanently eradicates infection in about 40% of cases. It has long been suspected that host genetic factors are key determinants for the control of HCV infection.
Design We will review in this study four genome-wide association studies (GWAS) and two large candidate gene studies that assessed the role of host genetic variation for the natural and treatment-induced control of HCV infection.
Results The studies consistently identified genetic variation in interleukin 28B (IL28B) as the strongest predictor for the control of HCV infection. Importantly, single nucleotide polymorphisms (SNPs) in IL28B strongly predicted both spontaneous and treatment-induced HCV recovery. IL28B is located on chromosome 19 and encodes interferon-λ, a type III interferon with antiviral activity, which is mediated through the JAK-STAT pathway by inducing interferon-stimulated genes. The SNPs identified in the GWAS are in high linkage disequilibrium with coding or functional non-coding SNPs that might modulate function and/or expression of IL28B. The role of the different IL28B alleles on gene expression and cytokine function has not yet been established.
Conclusions These findings provide strong genetic evidence for the influence of interferon-λ for both the natural and treatment-induced control of HCV infection, and support the further investigation of interferon-λ for the treatment of chronic hepatitis C. Furthermore, genetic testing before HCV therapy could provide important information towards an individualized HCV treatment.
Received 9 April 2010; accepted 9 June 2010
DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1365-2362.2010.02337.x About DOI