Host - hepatitis C viral interactions: The role of genetics

JOURNAL OF HEPATOLOGY

卷:65

Review

Heim, Markus H.^1,2  Bochud, Pierre-Yves^3,4  George, Jacob^5,6 

[1] Univ Basel Hosp, Div Gastroenterol & Hepatol, Petersgraben 4, CH-4031 Basel, Switzerland

[2] Univ Basel, Dept Biomed, Hebelstr 20, CH-4031 Basel, Switzerland

[3] Univ Lausanne Hosp, Infect Dis Serv, Rue Bugnon 46, CH-1011 Lausanne, Switzerland

[4] Univ Lausanne, Rue Bugnon 46, CH-1011 Lausanne, Switzerland

[5] Westmead Hosp, Westmead Inst Med Res, Storr Liver Ctr, Westmead, NSW, Australia

[6] Univ Sydney, Westmead, NSW, Australia

关键词: IL28B;    GWAS;    Interferon;    Hepatitis C virus;    Innate immunity;    Jak-STAT;    CD8(+) T cells;    T cell exhaustion;    Viral escape;    Fibrosis;    Hepatocellular cancer;    Haplotypes;   

DOI  :  10.1016/j.jhep.2016.07.037

来源: Elsevier

【 摘 要 】

Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFN lambda (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFN lambda 4 allele capable of producing a fully active IFN lambda 4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. In the chronic phase of HCV infection, the wild-type IFN lambda 4 genotype is strongly associated with an induction of hundreds of classical type I/type III IFN stimulated genes in hepatocytes. However, the activation of the endogenous IFN system in the liver is ineffective in clearing HCV, and is even associated with impaired therapeutic responses to pegylated (Peg)IFN alpha containing treatments. While the role of genetic variation in the IFN lambda locus to the outcome of CHC treatment has declined, it is clear that variation not only at this locus, but also at other loci, modulate clinically important liver phenotypes, including inflammation, fibrosis progression and the development of hepatocellular cancer. In this review, we summarize current knowledge about the role of genetics in the host response to viral hepatitis and the potential future evolution of knowledge in understanding host-viral interactions. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free