Basal core-promoter mutant of hepatitis B virus and progression of liver disese in hepatitis B e antigen-negative chronic hepatitis B
Basal core-promoter mutant of hepatitis B virus and progression of liver disese in hepatitis B e antigen-negative chronic hepatitis B
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DOI：
10.1111/j.1478-3231.2005.01041.x
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发表时间：
2005-06-01
影响因子：
6.7
通讯作者：
Kao, JH
中科院分区：
文献类型：
--
作者：
Lin, CL;Liao, LY;Kao, JH
背景/目的：乙型肝炎e抗原(HBeAg)阴性的慢性乙型肝炎和HBeAg阳性的慢性肝炎的长期预后是不同的。然而，在这种特殊的临床环境中，导致肝病进展的分子病毒学因素仍然很大程度上是未知的。因此，我们调查了台湾地区HBeAg阴性慢性乙肝患者的临床和病毒学特征与乙肝病毒(乙肝病毒)基因分型以及前C/基本核心-启动子突变之间的关系。方法：对174例HBeAg阴性慢性乙肝患者(其中62例为非活动性携带者，112例为不同肝病阶段)进行了HBVDNA前C区和基本C区基因分型及序列分析。结果：高龄(50岁)(优势比9.0 9；95%可信区间3.2 2~2 5，P<0.0 1)和基本核心启动子变异(优势比4.12；95%CI，1.4 1~12.0 3，P=0.0 1)的乙肝病毒携带者与肝硬变和肝细胞癌的发生有关。进一步分析与肝硬变和肝细胞癌发生相关的性别相关危险因素，发现男性携带者基础核心-启动子突变仅与肝硬变和肝细胞癌的发生有关(优势比为4.35；95%可信区间为1.30~14.52，P=0.02)。结论：高龄患者和携带基本核心启动子变异的患者发生肝硬变和肝细胞癌的风险显著增加。此外，台湾地区HBeAg阴性慢性乙型肝炎患者肝病进展的性别差异可能与基础核心-启动子突变有关。
Background/Aims: The long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are distinct from those in HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in this special clinical setting remain largely unknown. We thus investigated the association of hepatitis B virus (HBV) genotypes as well as precore/basal core-promoter mutations with the clinical and virological characteristics of patients with HBeAg-negative chronic hepatitis B in Taiwan. Methods: HBV genotypes and sequences of precore and basal core-promoter regions of the HBV genome were determined in 174 HBeAg-negative chronic HBV infection patients including 62 inactive carriers and 112 with different stages of liver disease. Results: HBV carriers with older age (> 50 years) (odds ratio, 9.09; 95% confidence interval (CI), 3.22-25, P < 0.001) and basal core-promoter mutant of HBV (odds ratio, 4.12; 95% Cl, 1.41-12.03, P = 0.01) were associated with the development of liver cirrhosis and hepatocellular carcinoma (HCC). The gender-related risk factors associated with the development of liver cirrhosis and HCC were further analyzed, and basal core-promoter mutant was only associated with the development of liver cirrhosis and HCC in male carriers (odds ratio, 4.35; 95% CI, 1.30-14.52, P = 0.02). Conclusions: The risk of development of liver cirrhosis and HCC is significantly increased in patients with advanced age as well as with basal core-promoter mutant of HBV. In addition, basal core-promoter mutant might contribute to the gender difference of the progression of liver disease in HBeAg-negative chronic hepatitis B in Taiwan.