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[韩国慢性乙型肝炎病毒感染患者前核心区和核心启动子突变的患病率及临床意义]

[The prevalence and clinical significance of precore and core promoter mutations in Korean patients with chronic hepatitis B virus infection].

作者信息

Kim Hyung Joon, Yoo Byung Chul

机构信息

Department of Gastroenterology, College of Medicine, Chung Ang University, Seoul, Korea.

出版信息

Taehan Kan Hakhoe Chi. 2002 Jun;8(2):149-56.

Abstract

BACKGROUND/AIMS: Precore and core promoter mutations of hepatitis B virus (HBV) have been reported in Korea but their prevalence and clinical significance have not been determined. The aims of this study were to determine the prevalence of precore and core promoter mutations and their relationships to hepatitis B e antigen (HBeAg) status, viral replication level, and severity of liver disease in Korea.

METHODS

Among the patients who visited the Liver Diseases Clinics (Chung Ang University Hospital) between December 1998 and August 1999, 150 patients were randomly selected: 50 HBeAg-positive HBV-DNA positive patients by a branched DNA (bDNA) assay, 50 HBeAg-negative bDNA-positive patients, and 50 HBeAg-negative bDNA-negative patients. Serum HBV-DNA was amplified by a polymerase chain reaction (PCR) in these patients and the core promoter/precore HBV sequence was determined in 135 of the patients whose sera were positive for HBV-DNA by PCR.

RESULTS

All of the 135 determined HBV-DNA sequences had HBV genotype with T at nucleotide 1858. Precore mutation (A1896) was detected in 95.7% of HBeAg-negative bDNA-positive patients and 94.9% of HBeAg-negative bDNA-negative patients. In HBeAg-positive patients 88% had wild type and 12% had mixture of wild type and A1896 mutant. Core promoter TA mutation (T1762/A1764) was detected in 93.5% of HBeAg-negative bDNA-positive patients, 94.9% of HBeAg-negative bDNA-negative patients and 74% of HBeAg-positive patients. No correlation was found between the presence of precore/core promoter mutations and liver disease severity or HBV-DNA levels.

CONCLUSION

Precore stop codon mutation occurred almost invariably, along with HBeAg seroconversion, irrespective of subsequent viral replication levels or disease severity. Core promoter TA mutation was frequent both in the HBeAg-positive patients and HBeAg-negative patients irrespective of viral replication levels or disease severity.

摘要

背景/目的:韩国已报道了乙型肝炎病毒(HBV)前核心区和核心启动子突变,但它们的流行情况及临床意义尚未明确。本研究的目的是确定韩国前核心区和核心启动子突变的流行情况,以及它们与乙肝e抗原(HBeAg)状态、病毒复制水平和肝病严重程度的关系。

方法

在1998年12月至1999年8月期间就诊于肝病门诊(忠南大学医院)的患者中,随机选取150例患者:50例通过分支DNA(bDNA)检测为HBeAg阳性且HBV-DNA阳性的患者,50例HBeAg阴性且bDNA阳性的患者,以及50例HBeAg阴性且bDNA阴性的患者。对这些患者的血清HBV-DNA进行聚合酶链反应(PCR)扩增,并对135例血清HBV-DNA经PCR检测为阳性的患者测定核心启动子/前核心区HBV序列。

结果

135个已测定的HBV-DNA序列均为核苷酸1858处为T的HBV基因型。前核心区突变(A1896)在95.7%的HBeAg阴性且bDNA阳性患者和94.9%的HBeAg阴性且bDNA阴性患者中被检测到。在HBeAg阳性患者中,88%为野生型,12%为野生型与A1896突变体的混合型。核心启动子TA突变(T1762/A1764)在93.5%的HBeAg阴性且bDNA阳性患者、94.9%的HBeAg阴性且bDNA阴性患者以及74%的HBeAg阳性患者中被检测到。未发现前核心区/核心启动子突变的存在与肝病严重程度或HBV-DNA水平之间存在相关性。

结论

前核心区终止密码子突变几乎总是与HBeAg血清学转换同时发生,而与随后病毒复制水平或疾病严重程度无关。核心启动子TA突变在HBeAg阳性患者和HBeAg阴性患者中均很常见,与病毒复制水平或疾病严重程度无关。

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