Fukuda R, Ishimura N, Kushiyama Y, Moriyama N, Ishihara S, Chowdhury A, Tokuda A, Sakai S, Akagi S, Watanabe M, Fukumoto S
Second Department of Internal Medicine, Shimane Medical University, Japan.
Microbiol Immunol. 1996;40(7):481-8. doi: 10.1111/j.1348-0421.1996.tb01098.x.
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.
具有X基因突变的乙型肝炎病毒（HBV）一直被认为是慢性肝炎的病原体，这类慢性肝炎缺乏已知肝炎病毒的血清学标志物。本研究的目的是再次确认具有X基因突变的HBV是否与这些血清学上“隐匿”的非B、非C（NBNC）慢性肝炎、酒精性肝病（ALD）和自身免疫性肝炎（AIH）有关。从血清中扩增HBV DNA，并对30例NBNC慢性肝炎患者进行测序，与20例ALD患者和5例AIH患者进行比较。通过巢式聚合酶链反应在21例（70%）NBNC慢性肝炎患者中检测到HBV DNA，而在ALD患者中仅1例（5%）检测到HBV DNA，AIH患者中未检测到。在检测到的21份HBV DNA中，有18份（85.7%）在X区域远端有相同的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，并产生了一个翻译终止密码子，使X蛋白从C末端截短了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上“隐匿”的NBNC慢性肝炎病例密切相关，且这类突变HBV DNA的群体并不一致。
