目的：探讨乙型肝炎病毒（HBV）前C/C基因启动子区变异与HBeAg阴性慢性乙型肝炎（CHB）患者肝组织病理变化的关系。方法：将2012年4月至2013年12月在广州市第八人民医院住院诊治所有伴肝活检的HBeAg阴性CHB患者71例纳入本项研究，提取血清DNA后通过巢式PCR扩增HBV的S基因区与前C／C基因启动子区并测序分析，Logistic回归分析与显著性肝脏组织学异常相关的病毒性因素指标。结果：基因型B患者组与基因型C患者组比较，显著性肝脏炎症发生率（15.8%vs．27.3%，χ2=1.398，P=0.237）及显著性肝纤维化发生率（71.1% vs．84.4%，χ2=1.926，P =0.165）均无显著差异。纳入年龄、性别、HBV基因型以及变异位点（T1753V、A1762T／G1764A、A1846T和G1896A）进行Logistic回归分析，HBV基因的A1762T／G1764A变异与显著性肝脏炎症相关（OR =4.296，P =0.037），而年龄、性别、基因型和其他位点变异与显著性肝组织病理学改变无显著相关性（均P >0.05）。结论：HBV前C／C基因区变异可能可作为评估肝组织病理变化的生化指标。%Objective To investigate the relationship between HBV mutations in the precore (PC)/core promoter region and the liver histological changes in HBeAg negative CHB patients. Method A total of 71 HBeAg negative CHB patients with liver biopsy from April 2012 to Dec 2013 were enrolled. DNA was extracted from blood serum, then the HBV S gene and PC/core promoter region were amplified by semi-nested PCR and sequenced. The relationship between significant liver histological changes and viral factors were analyzed by Logistic regression analysis. Results The incidence of significant necroinflammation (15.8% vs. 27.3%, χ2 =1.398, P = 0.237) and significant fibrosis (71.1% vs. 84.4%, χ2= 1.926, P = 0.165) were found to be similar between patients infected with HBV genotype B and genotype C . By Logistic regression analysis including risk factors of age, sex, HBV genotype and mutations (T1753V,A1762T/G1764A,A1846T and G1896A), the A1762T/G1764A mutation in HBV associated with significant necroinflammation (OR = 4.296, P = 0.037), while factors of age, sex, genotype and other mutation were not associated with significant liver histological changes. (all P > 0.05). Conclusion Mutation in PC/core promoter region of HBV may act as a marker to evaluate the liver histological changes.
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