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免疫血清转化前后,乙肝病毒C基因型完整序列在非活动性携带者与肝细胞癌患者之间的比较。

Comparison of complete sequences of hepatitis B virus genotype C between inactive carriers and hepatocellular carcinoma patients before and after seroconversion.

作者信息

Ito Kiyoaki, Tanaka Yasuhito, Kato Michio, Fujiwara Kei, Sugauchi Fuminaka, Sakamoto Tomoyuki, Shinkai Noboru, Orito Etsuro, Mizokami Masashi

机构信息

Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho, Nagoya 467-8601, Japan.

出版信息

J Gastroenterol. 2007 Oct;42(10):837-44. doi: 10.1007/s00535-007-2100-6. Epub 2007 Oct 15.

Abstract

BACKGROUND

Most patients who acquire chronic hepatitis B virus (HBV) infection by perinatal transmission become inactive carriers (IC) after hepatitis B e (HBe) antigen seroconversion, whereas some patients have persistent abnormal serum transaminase levels and develop hepatocellular carcinoma (HCC) in the anti-HBe-positive phase. The aim of this study was to investigate the HCC-related mutations of HBV.

METHODS

Complete sequences of HBV were examined among eight IC and eight HCC patients infected with HBV genotype C before and after seroconversion.

RESULTS

The frequency of the T1653 mutation tended to be higher among HCC patients after seroconversion (16.7% vs. 62.5%; P = 0.086). The prevalence of a basal core promoter double mutation (T1762/A1764) was high among both IC and HCC patients after seroconversion (83.3% vs. 87.5%; P = 0.825). Among the HCC patients, a pre-S deletion mutant was detected in 62.5% patients before seroconversion, and in 37.5% patients after seroconversion. The core deletion mutant was also detected in 50% of HCC patients only before seroconversion. Deletion mutants of the pre-S or core region before seroconversion were significantly associated with HCC patients (0% vs. 62.5%; P = 0.007, 0% vs. 50%; P = 0.021, respectively).

CONCLUSIONS

Our data showed a significant association of pre-S and core deletion mutants before seroconversion with HCC development. The T1653 mutation after seroconversion was frequently found in HCC patients infected with HBV genotype C. These results suggest that mutations may be predictive factor for development of HCC.

摘要

背景

大多数围产期感染慢性乙型肝炎病毒(HBV)的患者在乙肝e抗原(HBe)血清学转换后成为非活动性携带者(IC),而一些患者血清转氨酶水平持续异常,并在抗-HBe阳性阶段发生肝细胞癌(HCC)。本研究旨在调查HBV与HCC相关的突变。

方法

对8例IC患者和8例感染C基因型HBV且发生血清学转换前后的HCC患者进行HBV全序列检测。

结果

血清学转换后,HCC患者中T1653突变频率有升高趋势(16.7%对62.5%;P = 0.086)。血清学转换后,IC患者和HCC患者中基础核心启动子双突变(T1762/A1764)的发生率均较高(83.3%对87.5%;P = 0.825)。在HCC患者中,62.5%的患者在血清学转换前检测到前S区缺失突变体,37.5%的患者在血清学转换后检测到。仅在血清学转换前,50%的HCC患者检测到核心区缺失突变体。血清学转换前前S区或核心区的缺失突变体与HCC患者显著相关(分别为0%对62.5%;P = 0.007,0%对50%;P = 0.021)。

结论

我们的数据显示血清学转换前前S区和核心区缺失突变体与HCC发生显著相关。血清学转换后,T1653突变在感染C基因型HBV的HCC患者中频繁出现。这些结果表明,突变可能是HCC发生的预测因素。

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