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Recognition of Genetic Factors Influencing the Progression of Hepatitis C

Potential for Personalized Therapy

  • Infectious Disorders
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Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. Hepatic fibrosis may develop in subjects with chronic HCV infection, culminating in cirrhosis and an increased risk of hepatocellular carcinoma. The rate of development of fibrosis varies substantially between individuals; while it is influenced by a number of demographic and environmental factors, these account for only a small proportion of the variability.

There are no clinical markers or tests that predict the rate of fibrosis progression in an individual subject. Thus, there has been increasing interest in the influence of host genetic factors on the rate of disease progression, and whether a genetic signature can be developed to reliably identify individuals at risk of severe disease. Numerous case-control, candidate gene, allele-association studies have examined the relationship between host single nucleotide polymorphisms or other genetic mutations and fibrosis in patients with chronic HCV infection. However, these studies have generally been irreproducible and disappointing. As seen with genetic studies for other diseases, small study cohorts and poor study design have contributed to limited meaningful findings. The successful determination of genetic signatures for fibrosis progression in chronic HCV will require multicenter collaborations using genome-wide association studies, with large, phenotypically well-defined sample sets. While these studies will require a significant financial commitment, a successful outcome offers the potential for personalized therapy and better patient management.

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Acknowledgments

Funding for the authors’ research was provided by the National Health and Medical Research Council of Australia, the Sasakawa Foundation (Royal Children’s Hospital), the Queensland Government’s Smart State Health and Medical Research Fund, and the Princess Alexandra Hospital Research and Development Foundation.

The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. School of Medicine, Southern Division, University of Queensland, Level 3, R Wing, Princess Alexandra Hospital, Woolloongabba, Ipswich Rd, Brisbane, Queensland, 4102, Australia

    Julie R. Jonsson, Andrew D. Clouston & Elizabeth E. Powell

  2. Genentech Inc., San Francisco, California, USA

    David M. Purdie

  3. Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia

    Elizabeth E. Powell

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  1. Julie R. Jonsson
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  2. David M. Purdie
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  3. Andrew D. Clouston
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  4. Elizabeth E. Powell
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Correspondence to Julie R. Jonsson.

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Jonsson, J.R., Purdie, D.M., Clouston, A.D. et al. Recognition of Genetic Factors Influencing the Progression of Hepatitis C. Mol Diag Ther 12, 209–218 (2008). https://doi.org/10.1007/BF03256286

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