Human genetics of HCV infection phenotypes in the era of direct-acting antivirals

Abstract

The recent introduction of direct-acting antivirals (DAAs) has revolutionized hepatitis C virus (HCV) therapy by improving virus eradication rates to over 90% in most patient groups. However, the impact of DAAs on global disease burden is currently limited, and a large number of chronically infected individuals remain at risk of developing liver complications, such as liver cirrhosis and hepatocellular carcinoma (HCC). The identification of patients at risk of liver complications and a greater understanding of the biological mechanisms involved in HCV disease progression might improve disease control. Recent genome-wide association and exome sequencing studies have identified several host genetic variants influencing the progression of liver fibrosis and the development of HCC associated with HCV infection and are reviewed here. Interestingly, some of the genetic variants associated with those HCV-associated liver complications were also associated with the clinical course of non-viral chronic hepatitis. Future challenges include the incorporation of this genetic information into clinical risk models for personalized disease management and the study of emerging phenotypes such as liver fibrosis regression and HCC development after HCV eradication.

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Acknowledgement

We thank Laurent Abel, Jean-Laurent Casanova and both branches of the Laboratory of Human Genetics of Infectious Diseases for helpful discussion and support. The Necker branch of the Laboratory of Human Genetics of Infectious Diseases is supported by The National Agency for Research on AIDS and Viral Hepatitis (ANRS), National Institute of Health and Medical Research (INSERM), Paris Descartes University, the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID) and the French National Research Agency under the “Investments for the future” program (Grant number ANR-10-IAHU-01).

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Nahon, P., Cobat, A. Human genetics of HCV infection phenotypes in the era of direct-acting antivirals. Hum Genet 139, 855–863 (2020). https://doi.org/10.1007/s00439-020-02136-4

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