HEPATITIS-B VIRUS PRECORE MUTATION AND FULMINANT-HEPATITIS IN THE UNITED-STATES - A POLYMERASE CHAIN REACTION-BASED ASSAY FOR THE DETECTION OF SPECIFIC MUTATION
HEPATITIS-B VIRUS PRECORE MUTATION AND FULMINANT-HEPATITIS IN THE UNITED-STATES - A POLYMERASE CHAIN REACTION-BASED ASSAY FOR THE DETECTION OF SPECIFIC MUTATION
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DOI：
10.1172/jci117006
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发表时间：
1994-02-01
影响因子：
15.9
通讯作者：
DIENSTAG, JL
中科院分区：
文献类型：
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作者：
LIANG, TJ;HASEGAWA, K;DIENSTAG, JL
在日本、以色列和南欧，B肝炎病毒（HBV）前C区突变导致HBeAg不产生的变异株与暴发性肝炎的发生有关，在这些地区，这种HBV毒株的流行似乎很常见。在美国等HBV感染不流行的地区，这种突变病毒在暴发性肝炎中的作用尚不清楚。我们开发了一种扩增难治性突变检测系统，以特异性地检测核苷酸位置1898处的G至A突变的存在，这是最常见的导致前C终止密码子的突变。此外，该方法提供了一种应变与另一种应变的相对比率的定量测量。使用该系统，我们测试了在美国发生的40例暴发性B型肝炎患者血清中存在的E-IBV株的终止密码子突变。成功地分析了28例患者的血清HBV DNA。在15例患者中观察到不同比例的野生型和突变株的混合物，11例仅为轻度型，2例仅为突变型。这些患者中有4例因HBV相关肝硬化接受了肝移植，移植后发生了暴发性HBV相关肝炎。移植前和移植后的血清样本从一个病人进行了分析：野生型和突变型HBV毒株的混合物中检测到的两个样本。我们的研究表明，野生型和突变型HBV毒株与暴发性肝炎有关，在美国的一些患者中，前C区突变以外的因素也有助于暴发性肝炎的发展。
Hepatitis B virus (HBV) variants with precore mutation(s) resulting in the absence of HBeAg production have been associated with the occurrence of fulminant hepatitis in Japan, Israel, and southern Europe, where the prevalence of this HBV strain appears common. In areas such as United States, where HBV infection is not endemic, the role of this mutant virus in fulminant hepatitis is unknown. We developed an amplification refractory mutation detection system to detect specifically the presence of the G to A mutation at nucleotide position 1898, which is the most frequently observed mutation resulting in a precore stop codon. In addition, this method provided a quantitative measurement of the relative ratio of one strain to the other. Using this system, we tested E-IBV strains for the presence of the stop codon mutation in sera from 40 cases of fulminant hepatitis B occurring in the United States. Serum HBV DNAs from 28 patients were analyzed successfully. A mixture of wild-type and mutant strains in various ratios were observed in 15 patients, mild type exclusively in 11, and mutant exclusively in 2. Four of these patients had undergone liver transplantation for HBV-associated cirrhosis and developed fulminant HBV-associated hepatitis after transplantation. Pre- and posttransplant serum samples from one patient were analyzed: a mixture of wild-type and mutant HBV strains was detected in both samples. Our study demonstrated that both wild-type and mutant HBV strains are associated with fulminant hepatitis, and that in some patients in the United States, factors other than precore mutations contribute to the development of fulminant hepatitis.