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Viral hepatitis: Human genes that limit infection

https://doi.org/10.1016/j.bpg.2010.07.009Get rights and content

Treatment response and susceptibility to chronic viral hepatitis C and B may be modified by host genetic factors. The majority of genetic variants that confer a significant risk have been localized in genes involved in immune response. However, many findings could not be replicated and almost none of the identified risk factors had a noticeable impact on clinical decisions. In contrast, recent findings in independent large genome wide association studies confirmed genetic variants in the interferon gamma gene locus as strong predictors of outcome with outstanding clinical relevance. This review gives an overview on significant genetic susceptibility factors for susceptibility and treatment outcome in chronic viral hepatitis C and B that have been identified by the classical candidate gene approach and genome wide studies and also highlights some recent findings on genetic factors for common adverse drug reactions.

Introduction

Different investigational approaches have been used to identify genetic susceptibility factors for the natural course and treatment response in hepatitis C and B. Until the last decade the candidate gene approach was most frequently used. More recently genome wide association studies were applied to identify genetic predictors of spontaneous course and therapy outcome in chronic viral hepatitis C and B.

Section snippets

Interleukins, interferons and members of the tumour necrosis factor (TNF) family

Cytokines represent a large family of molecules, including the chemokines, interleukins, interferons and members of the tumour necrosis factor (TNF) family, all which play an important role for the initiation and regulation of immune responses and, therefore, might affect susceptibility to and/or natural course of HCV infection.

Recently, allelic variants in the IL28B gene have gained major scientific interest as several genome-wide association studies identified a panel of single nucleotide

Influence of individual genetic factors on treatment response in chronic viral hepatitis C and B

Chronic viral hepatitis C is difficult to cure and current standard treatment options suffer from variable success rates and considerable adverse effects [73]. A number of viral and clinical factors such as viral genotype, viral load, gender and stage of fibrosis have been identified as predictors of response. However, different studies suggest that genetically determined inter-individual differences in immune response may also have an impact on treatment outcome [4], [5], [6], [74], [75].

Side effects

Current standard of care for chronic HCV infection is treatment with peginterferon and ribavirin. However, this therapy is hampered by a number of possible side effects. Two of the most common being anaemia and neuropsychiatric symptoms.

Ribavirin dose reduction due to anaemia is associated with poorer treatment outcome. Recently, variants in the inosine triphosphatase (ITPA) gene, which confers a corresponding enzyme deficiency, have been associated with anaemia in patients treated with

Summary

The influence of individual genetic characteristics on the course of HCV and probably also HBV became obvious by the recent discovery of the impact of genetic variants in the interferon-lambda pathway. These observations stress the importance of further in depth genetic analysis in the field of pharmacogenomics in order to improve current therapy standards.

Practice points

  • Genetic testing is not yet a standard procedure for the identification of individual risks for spontaneous clearance or

Conflict of interest statement

None.

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