Liang T J, Hasegawa K, Rimon N, Wands J R, Ben-Porath E
Department of Medicine, Harvard Medical School, Boston, Mass.
N Engl J Med. 1991 Jun 13;324(24):1705-9. doi: 10.1056/NEJM199106133242405.
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.
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.
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.
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 hepatitis B infection. Naturally occurring viral mutations in the HBV genome may predispose the infected host to more severe liver injury.
以色列海法市有5名患者发生了医院内暴发性乙型肝炎疫情。先前的调查确定疑似传染源是一名乙型肝炎表面抗原携带者，其乙型肝炎e抗原抗体呈阳性且患有慢性肝病。我们检测了导致此次疫情的乙型肝炎病毒（HBV）毒株，以确定前核心区或核心区的特定突变。
通过聚合酶链反应扩增源患者、5名暴发性乙型肝炎患者以及5名急性自限性乙型肝炎对照患者血清中的病毒DNA来确定HBV的存在。然后对扩增的病毒HBV DNA样本进行克隆和测序。
病毒DNA的序列分析确定，源患者和5名暴发性肝衰竭患者中存在同一株在前核心区有两个突变的HBV突变体。该HBV突变体在X区、前核心区和核心区与其他已知HBV亚型有显著的序列差异。来自一名在疫情期间患有亚临床乙型肝炎的住院患者以及另外4名急性自限性乙型肝炎对照患者的克隆HBV DNA在前核心区均含有野生型序列。
在我们研究的此次疫情中，一种突变的乙型肝炎病毒株从一个共同来源传播给了5名患者，这些患者随后死于暴发性乙型肝炎感染。HBV基因组中自然发生的病毒突变可能使受感染宿主更容易发生更严重的肝损伤。
