Aritomi T, Yatsuhashi H, Fujino T, Yamasaki K, Inoue O, Koga M, Kato Y, Yano M
Institute for Clinical Research, Nagasaki Chuo National Hospital and WHO Collaborating Center for Reference and Research on Viral Hepatitis, Japan.
J Gastroenterol Hepatol. 1998 Nov;13(11):1125-32. doi: 10.1111/j.1440-1746.1998.tb00588.x.
It was recently reported that mutations in the precore and core promoter region of hepatitis B virus (HBV) are associated with fulminant hepatitis. The aim of this study was to investigate the association of mutations in the precore and core promoter region of HBV with fulminant and severe acute hepatitis. We studied Japanese patients with acute HBV infection, including seven patients with fulminant hepatitis, 12 with severe acute hepatitis and 41 with acute self-limited hepatitis. The presence of HBV mutants was examined by using a point mutation assay to detect a G to A transition at position 1896 in the precore region and an A to T transition at position 1762 and a G to A transition at position 1764 in the core promoter region. Significant differences in the proportion of mutations in the precore or core promoter region were present between patients with fulminant hepatitis and self-limited acute hepatitis (7/7 (100%) vs 4/41 (9.8%), P<0.01) and between severe acute hepatitis and self-limited acute hepatitis (6/12 (50.0%) vs 4/41 (9.8%), P<0.01). The frequency of mutation increased proportionately with the severity of disease in patients with acute HBV infection. Fulminant hepatitis B in Japan is closely associated with mutations in the core promoter and precore gene of HBV. Point mutation assays for HBV precore and core promoter analysis may be useful to predict the outcome of liver disease in patients with acute HBV infection.
最近有报道称，乙型肝炎病毒（HBV）前核心区和核心启动子区域的突变与暴发性肝炎有关。本研究的目的是调查HBV前核心区和核心启动子区域的突变与暴发性和严重急性肝炎之间的关联。我们研究了日本急性HBV感染患者，包括7例暴发性肝炎患者、12例严重急性肝炎患者和41例急性自限性肝炎患者。通过点突变检测法检测前核心区1896位的G到A转换、核心启动子区域1762位的A到T转换以及1764位的G到A转换，以检查HBV突变体的存在情况。暴发性肝炎患者与自限性急性肝炎患者在前核心区或核心启动子区域的突变比例存在显著差异（7/7（100%）对4/41（9.8%），P<0.01），严重急性肝炎患者与自限性急性肝炎患者也存在显著差异（6/12（50.0%）对4/41（9.8%），P<0.01）。急性HBV感染患者中，突变频率随疾病严重程度成比例增加。日本的暴发性乙型肝炎与HBV核心启动子和前核心基因的突变密切相关。用于HBV前核心区和核心启动子分析的点突变检测法可能有助于预测急性HBV感染患者的肝病结局。
