Association of HBV precore/core promoter variants with the degree of liver fibrosis in patients with HBeAg-positive chronic hepatitis B
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摘要: 目的探讨HBV前C/C基因启动子区变异与HBe Ag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HBe Ag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...Abstract: Objective To investigate the association of hepatitis B virus ( HBV) precore/core promoter variants with liver pathological changes in patients with HBe Ag-positive chronic hepatitis B ( CHB) . Methods A total of 148 HBe Ag-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. Results Of 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 T1753 V mutation, 35. 3% had A1762 T/G1764 A mutation, and 5. 9% had G1896 A mutation. The univariate logistic regression analysis showed that HBV A1762 T/G1764 A and G1896 A 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 A1762 T/G1764 A mutation ( odds ratio [OR]= 7. 098, P < 0. 001) and G1896 A mutation ( OR = 16. 816, P = 0. 007) were independently associated with marked liver fibrosis. Conclusion HBV precore/core promoter variants can be used as the risk factors for marked liver fibrosis in HBe Ag-positive CHB patients.
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