Characterization of hepatitis B virus genotypes/subgenotypes in 1301 patients with chronic hepatitis B in North China
Characterization of hepatitis B virus genotypes/subgenotypes in 1301 patients with chronic hepatitis B in North China
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DOI：
10.3760/cma.j.issn.0366-6999.2011.24.011
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发表时间：
2011-12-20
影响因子：
6.1
通讯作者：
Xu Dong-ping
中科院分区：
文献类型：
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作者：
Li Xiao-dong;Wang Lin;Xu Dong-ping
研究背景目前我国北方地区基于大样本测序的乙型肝炎病毒（HBV）B亚型流行率的数据仍然缺乏。此外，HBV基因型是否影响慢性B型肝炎（CH B）患者的耐药相关和HBeAg缺失相关突变仍在研究中。本研究旨在揭示中国北方地区HBV基因型/亚型的临床流行情况，以及HBV基因型分类与HBeAg丢失和耐药发生的临床意义。提取病毒DNA作为模板，采用巢式PCR扩增HBV基因组。结果HBV/B型190例（14.6%），HBV/C型1096例（84.2%），HBV/D型15例（1.2%）; HBV/B2（182/190）、HBV/C2（1069/1096）和HBV/D1（12/15）是各基因型中的主要亚型。北京地区C2的患病率（77.2%）低于北方其他地区（84.9%~ 87.4%）。HBV/C感染患者年龄较大，血清白蛋白水平较低，但HBV DNA和丙氨酸氨基转移酶（ALT）水平与HBV/B感染患者相似。HBV/C感染者中拉米夫定耐药突变rtM 204 I/N的发生率较高（44.9%vs.30.2%，P
Background There is still a paucity of data on hepatitis B virus (HBV) subgenotype prevalence in North China based on sequencing of large-size samples. In addition, whether HBV genotypes impact drug-resistance-associated and HBV e antigen (HBeAg)-loss-associated mutations in patients with chronic hepatitis B (CHB) is still under investigation. This study aimed to disclose clinical prevalence of HBV genotypes/subgenotypes in North China and the clinical implications of HBV genotype classification in respect to HBeAg loss and drug-resistant occurrence.Methods Sera were collected from 1301 nucleos(t)ide analog-experienced CHB patients. Viral DNA was extracted and used as template for HBV genome amplification by nested PCR. DNA sequencing was performed for the analysis of HBV genotypes/subgenotypes, drug-resistance-associated mutations in polymerase gene and HBeAg-loss-associated mutations in precore/basal core promoter (BCP) regions.Results HBV/B, HBV/C, and HBV/D were detected in 190 (14.6%), 1096 (84.2%), and 15 (1.2%) patients, respectively. HBV/B2 (182/190), HBV/C2 (1069/1096), and HBV/D1 (12/15) were predominant subgenotypes within individual genotypes. By contrast, C2 prevalence is relatively lower in Beijing area (77.2%) than in other north areas (84.9%-87.4%). HBV/C-infected patients had an older age and a lower serum albumin level but similar HBV DNA and alanine aminotransferase (ALT) levels compared to HBV/B-infected patients. HBV/C infection had a higher incidence of lamivudine-resistant mutations rtM204I/N (44.9% vs. 30.2%, P