Hepatitis B virus with X gene mutation is associated with the majority of serologically ''silent'' non-B, non-C chronic hepatitis
Hepatitis B virus with X gene mutation is associated with the majority of serologically ''silent'' non-B, non-C chronic hepatitis
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DOI：
10.1111/j.1348-0421.1996.tb01098.x
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发表时间：
1996-01-01
影响因子：
2.6
通讯作者：
Fukumoto, S
中科院分区：
文献类型：
--
作者：
Fukuda, R;Ishimura, N;Fukumoto, S
带有 X 基因突变的乙型肝炎病毒 (HBV) 已被认为是慢性肝炎的病原体，但没有已知肝炎病毒的血清学标记。本研究的目的是再次确认带有 X 基因突变的 HBV 是否与这些血清学上“沉默”的非乙型、非丙型 (NBNC) 慢性肝炎、酒精性肝病 (ALD) 和自身免疫性肝炎 (AIH) 相关，从 30 名 NBNC 慢性肝炎患者的血清中扩增 HBV DNA 并进行测序，并与 20 名 ALD 患者和 5 名 AIH 患者进行比较。通过巢式聚合酶链反应在 NBNC 慢性肝炎中的 21 名患者 (70%) 中鉴定出 HBV DNA，而 ALD 中只有 1 名患者 (5%) 且 AIH 中均未检测到 HBV DNA。 21 名鉴定出的 HBV DNA 中，有 18 名 (85.7%) 在 X 区远端有相同的 8 核苷酸缺失突变。该突变影响了 HBV DNA 的核心启动子和增强子 II 序列，并产生了翻译终止密码子，该翻译终止密码子将 X 蛋白从 C 末端截断了 20 个氨基酸。所有 HBV DNA 在第 83 个核苷酸处都有一个前核心突变，导致 HBe 抗原合成中断。这些结果表明 HBV 突变体与大多数血清学“沉默”的 NBNC 慢性肝炎病例密切相关，并且此类突变 HBV DNA 的群体并不均匀。
Hepatitis B virus (HBV) with X gene mutations has been a putative pathogen of chronic hepatitis without serological markers of known hepatitis viruses. The aim of this study was to reconfirm whether the HBV with the X gene mutation is associated with these serologically ''silent'' non-B, non-C (NBNC) chronic hepatitis, alcoholic liver disease (ALD) and autoimmune hepatitis (AIH), HBV DNA was amplified from serum and sequenced in 30 patients with NBNC chronic hepatitis in comparison with 20 patients with ALD and 5 patients with AIH. HBV DNA was identified in 21 patients (70%) in NBNC chronic hepatitis by nested polymerase chain reaction while only one patient (5%) in ALD and none in AIH showed HBV DNA, Eighteen (85.7%) of the 21 identified HBV DNAs had an identical 8-nucleotide deletion mutation at the distal part of the X region. This mutation affected the core promoter and the enhancer II sequence of HBV DNA and created a translational stop codon which truncated the X protein by 20 amino acids from the C-terminal end. All the HBV DNAs had a precore mutation at the 83rd nucleotide resulting in disruption of HBe antigen synthesis, These results indicate that HBV mutants are closely associated with the majority of serologically ''silent'' NBNC chronic hepatitis cases and the population of such mutant HBV DNAs is not uniform.