title: Presence of valine at position 27 of the hepatitis B virus core gene is associated with severe liver inflammation in Chinese patients.
abstract: Although it is widely believed that cytotoxic T lymphocytes (CTL) are responsible for severe flares of chronic hepatitis B that lead to liver failure, the published evidence to support this hypothesis is weak. The frequency of the I27V mutation in the HBV core gene, which produces a core 18-27 peptide capable of binding HLA-A*02, was compared in Chinese patients with severe liver inflammation (n = 77, including 39 with acute-on-chronic liver failure), moderate liver inflammation (n = 44) and inactive disease (n = 45). The frequency with which V27 reverted to the wild-type I27 was compared in severe liver inflammation patients who were either HLA-A*02 positive (n = 5) or negative (n = 5). The frequency of patients with a V27 positive HBV was higher in severe than in moderate liver inflammation (23.4% vs. 6.8%, P = 0.02) or inactive disease (23.4% vs. 4.7%, P = 0.006). After a minimum of 3 months follow-up, the frequency of reversion of V27 to the wild-type I27 was higher in HLA-A*02 positive than negative patients (5/5 vs. 1/5, P = 0.05). In summary, this is the first data showing an association between a specific amino acid mutation (I27V) and severe liver inflammation in patients with chronic hepatitis B. This mutation would produce a peptide that is known to bind HLA-A*02 and stimulate CTL. The high frequency of reversion to wild-type I27 in HLA-A*02 positive subjects suggests that CTL recognizing this peptide exist, and is consistent with the possibility that they contribute to the pathophysiology of severe liver inflammation in chronic hepatitis B.
authors.affiliation: Hepatology Unit and Key Laboratory for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.forename: Shiwu
authors.initials: S
authors.lastname: Ma
authors.forename: Xiaoxiong
authors.initials: X
authors.lastname: Hu
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.forename: Zhanhui
authors.initials: Z
authors.lastname: Wang
authors.forename: Yongyin
authors.initials: Y
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: William G H
authors.initials: WG
authors.lastname: Abbott
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005787:Gene Frequency; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D012720:Severity of Illness Index; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014633:Valine / Q000235:genetics
chemical_list: D015234:HLA-A Antigens; C524866:HLA-A*02 antigen; D015789:HLA-A2 Antigen; D006512:Hepatitis B Core Antigens; D014633:Valine