title: A complete genomic analysis of hepatitis B virus isolated from 516 Chinese patients with different clinical manifestations.
abstract: This study investigated features and clinical implications of HBV mutations in patients with different clinical manifestations. In total, 516 patients were enrolled in this study, including 131 patients with acute hepatitis B, 239 patients with chronic hepatitis B, and 146 patients with acute-on-chronic liver failure. HBV genotypes and mutations were analyzed by direct sequencing of complete viral genomes. Genotypes B2, C1, C2, and D1 accounted for 22.2%, 1.6%, 74.6%, and 1.6%, respectively. Genotype B was more frequently detected in patients with acute hepatitis B than those with chronic hepatitis B and acute-on-chronic liver failure. Deletion mutations were detected mostly in preS1 and preS2 regions and the detection rates were 3.8%, 19.7%, and 24.7% for acute hepatitis B, chronic hepatitis B and acute-on-chronic liver failure patients, respectively. Incidences of point mutation T53C (preS1F53L), G1613A (polR841K), G1775A and A1762T + G1764A in the basal core promoter region, G1896A and G1899A in precore region and A2189C (coreI97L) in core region increased along with acute hepatitis B, chronic hepatitis B, and acute-on-chronic liver failure. The mutation G1896A was independently associated with poor survival of patients with acute-on-chronic liver failure. The gradual increase of viral mutation incidences was also observed in three HLA-A2-restricted cytotoxic T lymphocyte epitopes from HLA-A2-positive patients, that is env188-196 (5.8%, 10.1%, 22.5%), core107-115 (4.3%, 4.6%, 19.7%), and x92-100 (1.4%, 20.2%, 33.8%). In conclusion, certain viral mutations in various regions of HBV genome are associated with disease progression of HBV infection.
authors.affiliation: Viral Hepatitis Research Laboratory, Institute of Infectious Diseases, Beijing, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Xu
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wan
authors.forename: Siyu
authors.initials: S
authors.lastname: Bai
authors.forename: Panyong
authors.initials: P
authors.lastname: Mao
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Mao
authors.forename: Shaojie
authors.initials: S
authors.lastname: Xin
authors.forename: Dongping
authors.initials: D
authors.lastname: Xu
mesh_terms: D000328:Adult; D002681:China; D004279:DNA, Viral / Q000737:chemistry* / Q000235:genetics*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D006509:Hepatitis B / Q000473:pathology* / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte
keywords: disease progression; epitope; full-length genome; hepatitis B virus; mutation