Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies


Akçay İ. M. , Katrinli Ş. , Ozdil K., Dinler Doğanay G. , Doganay L.

WORLD JOURNAL OF GASTROENTEROLOGY, vol.24, no.30, pp.3347-3360, 2018 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 24 Issue: 30
  • Publication Date: 2018
  • Doi Number: 10.3748/wjg.v24.i30.3347
  • Title of Journal : WORLD JOURNAL OF GASTROENTEROLOGY
  • Page Numbers: pp.3347-3360

Abstract

The clinical outcome of hepatitis B virus (HBV) infection depends on the success or failure of the immune responses to HBV, and varies widely among individuals, ranging from asymptomatic self-limited infection, inactive carrier state, chronic hepatitis, cirrhosis, hepatocellular carcinoma, to liver failure, depending on the success or failure of immune response to HBV. Genome-wide association studies (GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits. In this review, we discuss GWAS for persistence of HBV infection, antibody response to hepatitis B vaccine, and HBV-related advanced liver diseases. HBV persistence is associated with multiple genes with diverse roles in immune mechanisms. The strongest associations are found within the classical human leukocyte antigen (HLA) genes, highlighting the central role of antigen presentation in the immune response to HBV. Associated variants affect both epitope binding specificities and expression levels of HLA molecules. Several other susceptibility genes regulate the magnitude of adaptive immune responses, determining immunity vs tolerance. HBV persistence and nonresponse to vaccine share the same risk variants, implying overlapping genetic bases. On the other hand, the risk variants for HBV-related advanced liver diseases are largely different, suggesting different host-virus dynamics in acute vs chronic HBV infections. The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.