[B]Precore Mutations Occur Early in HBV Infection but Do Not Worsen Outcomes[/B]
By Brian Boyle, MD
Hepatitis B virus (HBV) precore mutants have been detected in 4%–10% of hepatitis B e antigen (HBeAg)-positive patients. It is currently thought that precore mutants emerge due to the selective pressure that occurs during the process of HBeAg seroconversion. Some studies have suggested that precore mutants are associated with more severe HBV-related liver disease, however, other studies have not confirmed this finding.
In a study published in The Journal of Infectious Diseases, investigators sought to assess the relationship between the development of precore and core promoter mutants and HBeAg seroconversion and the clinical effect of these mutations. The study enrolled 376 Chinese patients with chronic HBV seen at a hospital in Hong Kong between January 1999 and December 2001. The majority of these patients had no biochemical or clinical evidence of cirrhosis at presentation and subsequent follow-up; however, 20 presented with hepatocellular carcinoma and/or other cirrhosis-related complications, and 24 developed complications during the follow-up period.
The investigators found that 50% of patients <30 years of age had precore mutations and that there was no significant difference in the prevalence of precore mutations between the different age groups. The prevalence of precore mutations was 44.2% among HBeAg–positive patients and 56.5% in anti-HBe–positive patients (p=.031).
There were no significant differences in the alanine aminotransferase (ALT) and HBV DNA levels between patients with and without precore mutations. Further, the median HBV DNA level in anti-HBe–positive patients was elevated irrespective of the presence or absence of precore mutations. Finally, there was no difference in the prevalence of precore mutations between patients with and without complications.
Based upon these findings, the authors conclude, “to our knowledge this study was the first study to show that precore mutations occurred early in chronic HBV infection among the Chinese. The development of cirrhosis related complications and HCC was unrelated to precore mutations, but was probably due to the persistence of significant viremia after HBeAg seroconversion. Core promoter mutations might also play a role.”
10/23/02
Reference
M Yuen and others. Relationship between the Development of Precore and Core Promoter Mutations and Hepatitis B e Antigen Seroconversion in Patients with Chronic Hepatitis B Virus. The Journal of Infectious Diseases. 2002; 86:1335–8.
Copyright 2002 by HIV and Hepatitis. All Rights Reserved.
Reproduction of articles for personal or educational use is encouraged and does not require permission from the publisher.作者: cao1976 时间: 2015-8-17 17:54
一米阳光发表于 2008-12-11 14:42：
HBeAg阴性血清中乙肝病毒前C区变异分析
A study on the mutations of precore gene of hepatitis B virus genome in e antigen-negative sera
GUO Long-hua，HUANG Xian-zhang，ZHUANG Jun-hua.
Clinical Laboratory，Ersha Island Branch，Guangdong Provincial Hospital of Traditional Chinese Medicine，Guangzhou 510105，China
【Abstract】 Objective To investigate the mutations of precore gene in the e antigen-negative sera of patients with hepatitis B virus（HBV） infection and provide information for diagnosis and remedy of the diseases.Methods Precore gene were amplified by heminested-PCR from e antigen- negative sera and e antigen -postive sera，and the PCR products were sequenced，and the sequences were analysed.Results There was a hot point mutation in nucleotide position 1896G→A in precore gene.Conclusion The mutations in precore gene an cause e antigen sero conversion.
【Key words】 hepatitis B virus;mutation;precore gene
乙型肝炎病毒（hepatitis B virus，HBV）是不完全双链环状DNA病毒，基因组全长约3.2kb，为已知对人类致病的最小DNA病毒。HBV复制过程中要经过逆转录，由于逆转录酶缺乏有效的碱基校对功能，故HBV基因组比一般DNA病毒易发生变异。给疾病的预防、诊断、治疗和预后带来新的问题。有关HBV基因组的变异，近些年来一直是人们研究的热点。
HBV基因突变可在三个水平上影响HBeAg合成。基本核心启动子（BCP）突变属于在转录水平影响HBeAg合成。PreC基因提前出现终止子、启始密码子变异和移码突变，都可在翻译水平上影响HBeAg的合成。其中最常见的是nt 1896位G→A。如果nt 1862位G→T使第17位密码子由缬氨酸（valine，V）变成苯丙氨酸（phenylalanine，F），HBeAg前体信号肽就不能被切除，从而影响HBeAg分泌，属于翻译后水平上的影响。nt 1862位G→T变异易引发重症肝炎［4］，本次研究未发现此种变异。HBeAg可表达于肝细胞表面，成为细胞毒T细胞（cytotoxic T lymphocyte，CTL）的靶抗原，或通过抗体依赖细胞介导的细胞毒作用（antibody dependent cell mediated cytotoxicity，ADCC）以清除HBeAg感染的肝细胞。如果体内有HBV在复制，HBeAg阴转，反而有助于HBV免疫逃逸。HBeAg阴性的HBV感染者应引起人们重视。由于血液中的HBeAg可以干扰或抑制CTL对肝细胞膜上的HBcAg的攻击，故HBeAg的减少可使CTL对肝细胞膜上的HBcAg攻击得为强烈，从而引起严重的肝损害，导致重症肝炎。
【参考文献】
1 Bayraktar Y，Koseoglu A，Temizer A，et al.Relationship between the serum alamine aminotransferase level at the end of interferon treatment and histologic changes in wild type and precore mutant hepatitis B virus infections.J Viral Hepat，1996，3（3）:137-142.