title: X region mutations of hepatitis B virus related to clinical severity.
abstract: Chronic hepatitis B virus (HBV) infection remains a major health problem, with more than 240 million people chronically infected worldwide and potentially 650000 deaths per year due to advanced liver diseases including liver cirrhosis and hepatocellular carcinoma (HCC). HBV-X protein (HBx) contributes to the biology and pathogenesis of HBV via stimulating virus replication or altering host gene expression related to HCC. The HBV X region contains only 465 bp encoding the 16.5 kDa HBx protein, which also contains several critical cis-elements such as enhancer II, the core promoter and the microRNA-binding region. Thus, mutations in this region may affect not only the HBx open reading frame but also the overlapped cis-elements. Recently, several types of HBx mutations significantly associated with clinical severity have been described, although the functional mechanism in most of these cases remains unsolved. This review article will mainly focus on the HBx mutations proven to be significantly related to clinical severity via epidemiological studies.
authors.affiliation: Hong Kim, Seoung-Ae Lee, Bum-Joon Kim, Department of Biomedical Sciences, Microbiology and Immunology, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, Chongno-gu, Seoul 110-799, South Korea.
authors.forename: Hong
authors.initials: H
authors.lastname: Kim
authors.affiliation: Hong Kim, Seoung-Ae Lee, Bum-Joon Kim, Department of Biomedical Sciences, Microbiology and Immunology, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, Chongno-gu, Seoul 110-799, South Korea.
authors.forename: Seoung-Ae
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Hong Kim, Seoung-Ae Lee, Bum-Joon Kim, Department of Biomedical Sciences, Microbiology and Immunology, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, Chongno-gu, Seoul 110-799, South Korea.
authors.forename: Bum-Joon
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology; D009154:Mutation; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication / Q000235:genetics
chemical_list: D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: Clinical severity; Hepatitis B virus infection; Hepatitis B virus-X protein mutation; Hepatocellular carcinoma