Published online Aug 14, 2018. doi: 10.3748/wjg.v24.i30.3347
Peer-review started: April 10, 2018
First decision: May 16, 2018
Revised: May 29, 2018
Accepted: June 25, 2018
Article in press: June 25, 2018
Published online: August 14, 2018
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. 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.
Core tip: Genome-wide association studies (GWAS) have proven to be very useful in uncovering the host genetic factors that influence the clinical outcomes of hepatitis B virus (HBV) infection. Both class I and class II human leukocyte antigen (HLA) genes were implicated in persistence of HBV infection; associated variants affected antigen-binding specificities and expression levels of HLA molecules. HBV persistence and vaccine nonresponse were associated with the same HLA-DP allotypes, suggesting a critical role for the surface antigen in HBV pathogenesis. These findings might be exploited for development of potent vaccines based on alternative epitopes. GWAS for HBV-related pathologies identified many other immune-related genes, and provided genetic markers to detect the individuals at high risk for HBV-related diseases.