A HEPATITIS-B VIRUS MUTANT ASSOCIATED WITH AN EPIDEMIC OF FULMINANT-HEPATITIS
A HEPATITIS-B VIRUS MUTANT ASSOCIATED WITH AN EPIDEMIC OF FULMINANT-HEPATITIS
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DOI：
10.1056/nejm199106133242405
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发表时间：
1991-06-13
影响因子：
158.5
通讯作者：
BENPORATH, E
中科院分区：
文献类型：
--
作者：
LIANG, TJ;HASEGAWA, K;BENPORATH, E
背景 在以色列海法的5名患者中发生暴发性B型肝炎的医院内暴发。 既往调查确定疑似来源为一名B型肝炎表面抗原携带者，该人B e型肝炎抗原抗体阳性且患有慢性肝病。 我们检测了导致这一流行病的B型肝炎病毒（HBV）株，以确定前核心区或核心区的特异性突变。 通过聚合酶链反应扩增来源患者血清中的病毒DNA来鉴定HBV的存在，5名暴发性B型肝炎患者和5名急性自限性B型肝炎对照。 将扩增的HBV DNA进行克隆和测序。 病毒DNA的序列分析确定，在前C区有两个突变的相同HBV突变体存在于源患者和5名暴发性肝衰竭患者中。 该HBV突变体在X、前C区和核心区与其他已知HBV亚型有显著的序列差异。 克隆的HBV DNA来源于亚临床B型肝炎住院患者和其他4例急性自限性B型肝炎对照者，其前C区均含有野生型序列。 在我们研究的这次暴发中，一种变异的B型肝炎病毒株从一个共同的来源传播给5名患者，这些患者随后死于暴发性B型肝炎感染。 HBV基因组中自然发生的病毒突变可能使受感染的宿主易于发生更严重的肝损伤。
Background. A nosocomial outbreak of fulminant hepatitis B occurred in five patients in Haifa, Israel. Previous investigations identified the suspected source as a carrier of hepatitis B surface antigen who was positive for antibodies to hepatitis B e antigen and had chronic liver disease. We examined the strain of hepatitis B virus (HBV) that caused this epidemic, in order to identify specific mutations in the precore or core region.Methods. The presence of HBV was identified by polymerase-chain-reaction amplification of viral DNA in serum from the source patient, the five patients with fulminant hepatitis B, and five controls with acute, self-limited hepatitis B. The amplified viral HBV DNA samples were then cloned and sequenced.Results. Sequence analysis of viral DNA established that the same HBV mutant with two mutations in the precore region was present in the source patient and the five patients with fulminant hepatic failure. This HBV mutant had significant sequence divergence from other known HBV subtypes in the X, precore, and core regions. Cloned HBV DNA derived from a hospitalized patient who had subclinical hepatitis B at the same time as the outbreak and from four other control subjects with acute, self-limited hepatitis B all contained the wild-type sequence in the precore region.Conclusions. In the outbreak we studied, a mutant hepatitis B viral strain was transmitted from a common source to five patients who subsequently died of fulminant hepatitis B infection. Naturally occurring viral mutations in the HBV genome may predispose the infected host to more severe liver injury.