Host Genetic Determinants of Hepatitis B Virus Infection

Abstract

Chronic hepatitis B virus (HBV) infection is still a major health problem worldwide. Recently, a great number of genetic studies based on single nucleotide polymorphisms (SNPs) and genome-wide association studies have been performed to search for host determinants of the development of chronic HBV infection, clinical outcomes, therapeutic efficacy, and responses to hepatitis B vaccines, with a focus on human leukocyte antigens (HLA), cytokine genes, and toll-like receptors. In addition to SNPs, gene insertions/deletions and copy number variants are associated with infection. However, conflicting results have been obtained. In the present review, we summarize the current state of research on host genetic factors and chronic HBV infection, its clinical type, therapies, and hepatitis B vaccine responses and classify published results according to their reliability. The potential roles of host genetic determinants of chronic HBV infection identified in these studies and their clinical significance are discussed. In particular, HLAs were relevant for HBV infection and pathogenesis. Finally, we highlight the need for additional studies with large sample sizes, well-matched study designs, appropriate statistical methods, and validation in multiple populations to improve the treatment of HBV infection.

Advances in Targeting the Innate and Adaptive Immune Systems to Cure Chronic Hepatitis B Virus Infection

“…Modulation of B cell function and antibody production may represent another option for immunotherapy (87,177). A number of host genetic determinants have been identified to contribute to HBV control and pathogenesis (178). Many of these determinants play a role in immune control of HBV infection.…”

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

“…The vaccines achieved 99% seroprotection rates in healthy children and adolescents but approximately 5%-7% of the adult population are non-responders and the rate can increase to 70% in elderly persons and in special risk groups [13,129,136,142]. Also, genetically determined resistance may contribute to non-responsiveness to HBsAgS SVP vaccines [143][144][145]. At the molecular level, yeast-derived HBsAg SVPs are not N-glycosylated at the N146 position within the S-domain, in contrast to SVPs produced in mammalian cell lines and harvested from the cell culture medium, or isolated from the blood of chronic hepatitis B patients.…”

Editorial: genome‐wide association for developing chronic hepatitis B—authors’ reply

“…Numerous genetic studies have used either candidate gene or genome‐wide approaches to investigate host determinants of chronic HBV infection, with a focus on immune‐related genes 3 . The strongest associations have been demonstrated within the human leucocyte antigen ( HLA ) class II genes.…”