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HBV前C/C基因启动子区变异与HBeAg阳性慢性乙型肝炎肝纤维化程度的关系
Association of HBV precore/core promoter variants with the degree of liver fibrosis in patients with HBeAg-positive chronic hepatitis B
文章发布日期:2018年04月04日  来源:  作者:施海燕,李丽雅,何浩岚,等  点击次数:174次  下载次数:5次

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【摘要】:目的探讨HBV前C/C基因启动子区变异与HBeAg阳性慢性乙型肝炎(CHB)患者肝组织病理变化的关系。 方法将2012年4月-2013年12月在广州市第八人民医院住院诊治,且伴有肝活组织检查与相应冻存血清标本的HBeAg阳性CHB患者148例纳入本研究,提取血清DNA后通过巢式PCR扩增HBV前C/C基因启动子区并测序分析。计量资料方差不齐时2组间比较采用非参数Mann-Whitney U检验,计数资料2组间比较采用χ2检验,logistic回归分析与显著肝纤维化相关的参数。结果共116例(784%)患者肝活组织检查提示存在显著肝纤维化(≥S2)。ALT≤正常值上限患者组中,10例(58.8%)伴有显著肝纤维化,并发生T1753V(11.8%)、A1762T/G1764A(35.3%)和G1896A变异(5.9%)。单因素logistic回归分析显示,HBV基因A1762T/G1764A变异和G1896A变异与显著肝纤维化相关并具有统计学意义(P值均<0.05),而年龄、性别、基因型和其他变异位点与显著肝纤维不存在相关性。进一步多因素logistic回归分析显示,HBV基因的A1762T/G1764A变异(比值比7.098, P<0.001)和G1896A变异(比值比16.816, P=0.007)均与显著肝纤维化独立相关。结论HBV前C/C基因启动子区变异可作为评估HBeAg阳性CHB患者显著肝纤维化发生的危险因素。
【Abstract】:ObjectiveTo investigate the association of hepatitis B virus (HBV) precore/core promoter variants with liver pathological changes in patients with HBeAg-positive chronic hepatitis B (CHB). MethodsA total of 148 HBeAg-positive CHB patients who were hospitalized in Guangzhou Eighth People′s Hospital from April 2012 to December 2013, underwent liver biopsy, and had stored frozen serum samples were enrolled. Serum DAN was extracted and then nested PCR was used for the multiplication and sequencing of the HBV precore/core promoter region. The Mann-Whitney U test was used for comparison of continuous data with heterogeneity of variance between two groups, and the chi-square test was used for comparison of categorical data between two groups; a logistic regression analysis was performed to identify the parameters associated with marked liver fibrosis. ResultsOf all patients, 116 (78.4%) were found to have marked liver fibrosis (≥S2) by liver biopsy. Among the patients with ALT ≤upper limit of normal, 10 (58.8%) had marked liver fibrosis; 11.8% had T1753V mutation, 35.3% had A1762T/G1764A mutation, and 5.9% had G1896A mutation. The univariate logistic regression analysis showed that HBV A1762T/G1764A and G1896A mutations were significantly associated with marked liver fibrosis (P<0.05), while age, sex, HBV genotype, and other HBV mutations were not associated with marked liver fibrosis. The multivariate logistic regression analysis showed that HBV A1762T/G1764A mutation (odds ratio [OR]=7.098, P<0.001) and G1896A mutation (OR=16.816, P=0.007) were independently associated with marked liver fibrosis. ConclusionHBV precore/core promoter variants can be used as the risk factors for marked liver fibrosis in HBeAg-positive CHB patients.
【关键字】:肝炎病毒, 乙型; 肝硬化; 肝炎e抗原, 乙型; 启动区(遗传学); 危险因素
【Key words】:hepatitis B virus; liver cirrhosis; hepatitis B e antigens; promoter regions (genetics); risk factors
【引证本文】:SHI HY, LI LY, HE HL, et al. Association of HBV precore/core promoter variants with the degree of liver fibrosis in patients with HBeAg-positive chronic hepatitis B[J]. J Clin Hepatol, 2018, 34(5): 1020-1024. (in Chinese) 施海燕, 李丽雅, 何浩岚, 等. HBV前C/C基因启动子区变异与HBeAg阳性慢性乙型肝炎肝纤维化程度的关系[J]. 临床肝胆病杂志, 2018, 34(5): 1020-1024.

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