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乙型肝炎病毒亚基因型及核心启动子/前核心区变异与急性肝炎患者临床特征的关联

Association of hepatitis B virus subgenotypes and basal core promoter/precore region variants with the clinical features of patients with acute hepatitis.

作者信息

Hayashi Kazuhiko, Katano Yoshiaki, Takeda Yasushi, Honda Takashi, Ishigami Masatoshi, Itoh Akihiro, Hirooka Yoshiki, Nakano Isao, Yoshioka Kentaro, Toyoda Hidenori, Kumada Takashi, Goto Hidemi

机构信息

Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

出版信息

J Gastroenterol. 2008;43(7):558-64. doi: 10.1007/s00535-008-2197-2. Epub 2008 Jul 23.

Abstract

BACKGROUND

In endemic areas, including Japan, basal core promoter (BCP) and precore (PC) variants of hepatitis B virus (HBV) have been reported to be associated with the clinical outcome of acute hepatitis B patients. However, the associations of BCP/PC variants with clinical outcomes have not been observed in nonendemic areas. HBV subgenotypes, which show geographic variations in prevalence, may underlie this discrepancy in clinical outcomes. Little is known about the differences in the clinical and virological features of HBV subgenotypes and BCP/PC variants. The aim of this study was to investigate the distributions of subgenotypes and BCP/PC variants to identify clinical differences in acute hepatitis B patients.

METHODS

One hundred thirty-nine patients with acute hepatitis were enrolled. Nested polymerase chain reaction was used to amplify the pre-S region of HBV for genotyping and the BCP/PC regions for variant screening.

RESULTS

HBV subgenotypes A1 (n = 3), A2 (n = 28), B1 (n = 3), B2 (n = 9), C1 (n = 5), C2 (n = 84), C variant (n = 1), D2 (n = 3), and H (n = 3) were detected. BCP/PC variants were not associated with progression to chronic hepatitis. Patients infected with subgenotype C2 who progressed to fulminant hepatic failure frequently carried variants at nucleotides non-T1753 and non-T1754 and T1762, A1764, and A1896.

CONCLUSIONS

BCP/PC variants would be associated with progression to fulminant hepatitis in subgenotype C2. Knowledge of HBV subgenotypes and BCP/PC variants is useful for developing strategies to treat acute hepatitis B patients.

摘要

背景

在包括日本在内的乙肝流行地区,据报道乙肝病毒(HBV)的基础核心启动子(BCP)和前核心(PC)变异与急性乙肝患者的临床结局相关。然而,在非流行地区尚未观察到BCP/PC变异与临床结局之间的关联。HBV亚基因型在流行率上存在地理差异,可能是导致临床结局出现这种差异的原因。目前对于HBV亚基因型和BCP/PC变异的临床及病毒学特征差异知之甚少。本研究的目的是调查亚基因型和BCP/PC变异的分布情况,以确定急性乙肝患者的临床差异。

方法

招募了139例急性肝炎患者。采用巢式聚合酶链反应扩增HBV的前S区域进行基因分型,扩增BCP/PC区域进行变异筛查。

结果

检测到HBV亚基因型A1(n = 3)、A2(n = 28)、B1(n = 3)、B2(n = 9)、C1(n = 5)、C2(n = 84)、C变异型(n = 1)、D2(n = 3)和H(n = 3)。BCP/PC变异与进展为慢性肝炎无关。进展为暴发性肝衰竭的C2亚基因型感染患者,常在非T1753、非T1754以及T1762、A1764和A1896核苷酸位点携带变异。

结论

BCP/PC变异可能与C2亚基因型进展为暴发性肝炎有关。了解HBV亚基因型和BCP/PC变异对于制定治疗急性乙肝患者的策略具有重要意义。

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