Chronic hepatitis B virus (HBV)
infection can cause a broad spectrum diseases, including from asymptomatic HBV carriers or cryptic
hepatitis, to acute
hepatitis, chronic hepatitis,
Liver cirrhosis and primary
hepatocellular carcinoma. The variable pattern and clinical outcome of the
infection were mainly determined by virological itself factors, host
immunological factors and genetic factors as well as the experimental factors. Among the human genetic factors, major candidate or identified genes involved in the process of HBV
infection fall into the following categories: (1) genes that mediate the processes of viral entry into hepatocytes, including genes involved in viral binding, fusion with cellular membrane and transportation in target cells; (2) genes that modulate or control the immune response to HBV
infection; (3) genes that participate in the pathological alterations in liver tissue; (4) genes involved in the development of
liver cirrhosis and
hepatocellular carcinoma associated with chronic HBV
infection, including genes related to mother-to-infant transmission of HBV
infection; and (5) those that contribute to resistance to
antiviral therapies. Most of the reports of human genes associated with HBV
infection have currently focused on HLA associations. For example, some investigators reported the association of the HLA class II alleles such as DRB1*1302 or
HLA-DR13 or DQA1*0501-DQB1*0301-DQB1*1102 haplotypes with acute and/or
chronic hepatitis B virus infection, respectively. Several pro-inflammatory
cytokines such as Th1
cytokines (including IL-2 and IFN-gamma) and
TNF-alpha have been identified to participate the process of viral clearance and host immune response to HBV. In contrast, the Th2
cytokine IL-10 serves as a potent inhibitor of Th1 effector cells in HBV diseases. The MBP polymorphisms in its encoding region were found to be involved in
chronic infection. Thus, reports from various laboratories have shown some inconsistencies with regard to the effects of host genetic factors on HBV clearance and persistence. Since genetic interactions are complex, it is unlikely that a single allelic variant is responsible for HBV resistance or susceptibility. However, the collective influence of several single nucleotide polymorphisms (SNPs) or haplotype (s) may underlie the natural combinational or synergistic protection against HBV. The future study including the multi-cohort collaboration will be needed to clarify these preliminary associations and identify other potential candidate genes. The ongoing study of the distributions and functions of the implicated allele polymorphisms will not only provide insight into the pathogenesis of HBV
infection, but may also provide a novel rationale for new methods of diagnosis and therapeutic strategies.