Understanding the Host Genetics of Chronic Hepatitis B and C

[Guest guest]

https://www.thieme-connect.com/ejournals/abstract/sld/doi/10.1055/s-0031-1276642

Semin Liver Dis 2011; 31(2): 115-127

DOI: 10.1055/s-0031-1276642

© Thieme Medical Publishers

Understanding the Host Genetics of Chronic Hepatitis B and C

Mark Thursz1, Leland Yee2, Salim Khakoo1

1 Hepatology and Gastroenterology Section, Department of Medicine, Imperial

College, London, United Kingdom

2 Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania

ABSTRACT

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.

[Guest guest]

https://www.thieme-connect.com/ejournals/abstract/sld/doi/10.1055/s-0031-1276642

Semin Liver Dis 2011; 31(2): 115-127

DOI: 10.1055/s-0031-1276642

© Thieme Medical Publishers

Understanding the Host Genetics of Chronic Hepatitis B and C

Mark Thursz1, Leland Yee2, Salim Khakoo1

1 Hepatology and Gastroenterology Section, Department of Medicine, Imperial

College, London, United Kingdom

2 Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania

ABSTRACT

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.