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Understanding the host genetics of chronic hepatitis B and C

Record type: Article

The outcome of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are heterogeneous, ranging from an asymptomatic self-limiting infection to cirrhosis and hepatocellular carcinoma. Several viral environmental and demographic variables have been identified as determinants of disease outcome, but these fail to explain a large proportion of the variability. Evidence from twin studies suggests that the host genetic background is an important contributor to disease outcome. Identification of genes that influence the outcome of infection has been attempted using a wide spectrum of approaches including candidate gene disease association studies, genome-wide scanning in affected sibling pairs and most recently genome-wide association studies. We summarize the main findings from a large number of studies in this review. Many studies have focused on the MHC loci from which several reproducible disease associations have been identified. More recently, genome-wide association studies have identified an important locus within the IL-28 - Il-29 region on chromosome 29, which appears to be a major determinant of the treatment response in patients infected with HCV and also a determinant of spontaneous resolution of infection. Translation of the genetic architecture of chronic viral hepatitis into therapeutic opportunities has been slow to proceed. One clinical trial and one drug development program have been based on genetic discoveries. The use of IL-28B genotyping to predict the response to pegylated interferon and ribavirin may also find its way into clinical practice. Indeed, stratification of clinical trial populations based on IL-28B genotype is already considered mandatory.

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Citation

Thursz, Mark, Yee, Leland and Khakoo, Salim I. (2011) Understanding the host genetics of chronic hepatitis B and C Seminars in Liver Disease, 31, (2), pp. 115-127. (doi:10.1055/s-0031-1276642). (PMID:21538279).

More information

Published date: May 2011
Keywords: genome-wide association study, genetic susceptibility, interferon lambda, complex trait, genetic architecture
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337519
URI: http://eprints.soton.ac.uk/id/eprint/337519
ISSN: 0272-8087
PURE UUID: 86bb05ca-a634-4341-a701-2cb06a9ccf91

Catalogue record

Date deposited: 26 Apr 2012 14:29
Last modified: 18 Jul 2017 06:02

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Contributors

Author: Mark Thursz
Author: Leland Yee
Author: Salim I. Khakoo

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