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乙型肝炎病毒核心启动子突变与病毒载量的相关性在 HBeAg(+)和 HBeAg(-)患者中不同。

Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients.

机构信息

Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Lippo Karawaci, Tangerang, 15810, Indonesia.

出版信息

World J Gastroenterol. 2011 Feb 14;17(6):708-16. doi: 10.3748/wjg.v17.i6.708.

Abstract

AIM

To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.

METHODS

Sixty-four patients with chronic hepatitis, 65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study. HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing. Viral load was measured by real-time polymerase chain reaction.

RESULTS

Of 179 patients, 108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted. The A1896 mutation was not found in HBeAg(+) patients, however, this mutation was detected in 70.7% of HBeAg(-) patients. This mutation was frequently found when HBeAg was not expressed (87.7%), compared to that found in HBeAg seroconverted patients (65.1%). The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P = 0.004). The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients, however, the prevalence of this mutation did not significantly differ among the two groups (P = 0.054). In HBeAg(+) patients, the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001). The A1899 mutation did not correlate with HBV DNA (P = 0.609). In HBeAg(-) patients, the T1762/A1764 mutation alone was not correlated with HBV DNA (P = 0.095), however, the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).

CONCLUSION

The percentage of HBeAg(-) patients is high in Indonesia, and most of the HBeAg(-) patients had been seroconverted. The A1896 mutation was most likely the major cause of HBeAg loss. The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients, but not in HBeAg(-) patients.

摘要

目的

鉴定乙型肝炎 e 抗原(HBeAg)的流行情况,并评估印度尼西亚患者乙型肝炎病毒(HBV)核心启动子突变与病毒载量之间的相关性。

方法

本研究纳入了 64 例慢性肝炎患者、65 例肝硬化患者和 50 例肝细胞癌患者。采用酶联免疫吸附试验检测 HBeAg 和乙型肝炎 e 抗体(HBeAb),采用测序分析突变。实时聚合酶链反应测量病毒载量。

结果

在 179 例患者中,有 108 例(60.3%)为 HBeAg(-),其中 86 例(79.6%)HBeAg(-)患者发生了血清转换。在 HBeAg(+)患者中未发现 A1896 突变,但在 70.7%的 HBeAg(-)患者中检测到该突变。当 HBeAg 不表达时,该突变更为常见(87.7%),而在 HBeAg 血清转换患者中则为 65.1%。A1899 突变在 HBeAg(-)患者中也比在 HBeAg(+)患者中更为常见(P=0.004)。T1762/A1764 突变在 HBeAg(+)和 HBeAg(-)患者中均较常见,但两组之间该突变的发生率无显著差异(P=0.054)。在 HBeAg(+)患者中,T1762/A1764 突变与较低的 HBV DNA 相关(P<0.001)。A1899 突变与 HBV DNA 不相关(P=0.609)。在 HBeAg(-)患者中,单独的 T1762/A1764 突变与 HBV DNA 不相关(P=0.095),但 T1762/A1764 或 A1896 突变的存在与 HBV DNA 增加相关(P<0.001)。

结论

印度尼西亚 HBeAg(-)患者的比例较高,且多数 HBeAg(-)患者已发生血清转换。A1896 突变可能是 HBeAg 丢失的主要原因。在 HBeAg(+)患者中,单独的 T1762/A1764 突变与较低的病毒载量相关,但在 HBeAg(-)患者中则不相关。

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