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目的检测乙肝病毒核心启动子(basic core promoter,BCP)区变异位点在乙肝相关疾病中的变异频率,评估乙肝病毒变异在终末期肝病发生中的风险。方法收集2 093例HBV无症状携带者(asymptomatic HBsAg carrier,ASC)、慢性乙型肝炎(chronic hepatitis B,CHB)、肝硬化(liver cirrhosis,LC)和肝细胞癌(hepatocellular carcinoma,HCC)患者,应用测序法检测HBV位点变异;运用病例对照研究方法,以ASC组为对照,研究乙肝病毒核心启动子区的变异与乙肝相关疾病发生间的关系。应用非条件Logistic回归法分析校正年龄和性别后HBV变异在CHB、LC和HCC发生中的风险。结果 HCC组中除T1768A变异外,其余变异位点的变异频率均大于30%,而在ASC组中无变异位点的变异频率超过30%;7个变异位点在4组人群中变异频率均逐渐增高(Ptrend<0.001);除T1768A位点外,其余变异在CHB、LC和HCC组中的校正比值比(adjusted odds ratio,AOR)均逐渐增加,A1762T/G1764A双突变在HCC发生中的AOR为13.91(95%CI 9.66～20.03);HBV BCP区位点累积变异频率在乙肝相关疾病进展过程逐渐递增(Ptrend<0.001)。结论随着HBV BCP区变异在HBV相关肝病进展过程中逐渐累加,终末期肝病的发病风险增加;HBV BCP区变异可作为早期预测HBV相关终末期肝病发生的潜在分子标记物。
Objective To detect the mutation frequency of hepatitis B virus (HBV) basic core promoter (BCP) region in hepatitis B related diseases and to evaluate the risk of hepatitis B virus mutation in the occurrence of end-stage liver disease. Methods A total of 2 093 patients with asymptomatic HBsAg carrier (ASC), chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) The HBV locus mutation was detected by sequencing method. The case-control study method was used to compare the variation of hepatitis B virus core promoter region and hepatitis B related disease with ASC group as control. Unconditional logistic regression was used to analyze the risk of HBV mutation in CHB, LC and HCC after age and gender correction. Results The frequency of mutation in all the other sites was greater than 30% except for T1768A in HCC group, while the mutation frequency was more than 30% in ASC group. The mutation frequency (P <0.001). Except T1768A, all the other mutations increased gradually in the CHB, LC and HCC groups (adjusted odds ratio (AOR)). The AOR of A1762T / G1764A double mutation in HCC Was 13.91 (95% CI 9.66-20.03). The cumulative frequency of HBV BCP loci increased progressively in the progression of hepatitis B related diseases (Ptrend <0.001). Conclusions As the HBV BCP mutation progressively increases during the progression of HBV-related liver disease, the risk of end-stage liver disease increases. HBV BCP mutation may serve as a potential molecular marker for early prediction of HBV-related end-stage liver disease.