乙型肝炎病毒前C区基因突变与乙型肝炎相关性慢加急性肝衰竭的关系

The relationship between gene mutation in the pre-C region of hepatitis B virus and acute-on-chronic liver failure associated with hepatitis B

目的探讨乙型肝炎病毒(HBV)前C区基因突变与乙型肝炎相关性慢加急性肝衰竭(ACLF)的关系。方法选择2020年5月至2023年5月中国人民解放军北部战区总医院收治的58例慢性乙型肝炎(CHB)患者设为CHB组、51例慢性乙型肝炎肝硬化(CHB-LC)患者设为CHB-LC组、52例乙型肝炎相关性慢加急性肝衰竭患者设为ACLF组。收集三组临床病理资料进行回顾性分析,采集三组外周血清HBVDNA,采用实时荧光定量聚合酶链反应(qRT-PCR)对三组HBV前C区基因进行扩增,而后进行基因测序,记录三组HBV前C区基因1896位变异情况。观察比较三组一般资料、乙型肝炎e抗原(HBeAg)、HBVDNA定量、甘油三酯(TG)、总胆固醇(TC)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、尿素氮(BUN)、前C区基因突变情况,对乙型肝炎相关性ACLF发病的相关影响因素进行logistic回归分析。结果三组患者的性别、年龄、病程、BMI、TG、TC、BUN差异均无统计学意义(均P>0.05),三组患者HBeAg、HBVDNA定量、ALT、AST差异有统计学意义(均P<0.05)。ACLF组的HBVDNA定量、ALT、AST均高于CHB组、CHB-LC组(均P<0.05)。ACLF组HBV前C区基因1896位突变率高于CHB组、CHB-LC组(均P<0.05);logistic多因素回归分析结果显示,HBVDNA定量、ALT、前C区基因突变是乙型肝炎相关性ACLF发病的独立影响因素(OR=1.042、1.570、1.413,P<0.05)。结论HBV前C区基因1896位变异在不同病程HBV感染患者中普遍存在,其变异发生率在CHB、CHB-LC、ACLF中呈逐渐升高趋势,HBVDNA和ALT升高、HBV前C区基因突变是乙型肝炎相关性ACLF发生的独立危险因素,临床需关注该类患者的病情进展。

Objective To explore the relationship between gene mutation in the pre-C region of hepatitis B virus(HBV)and acute-on-chronic liver failure(ACLF)associated with hepatitis B.Methods Fifty-eight patients with chronic hepatitis B(CHB)admitted to the General Hospital of Northern Theater Command of the Chinese People's Liberation Army from May 2020 to May 2023 were selected as the CHB group,51 patients with chronic hepatitis B liver cirrhosis(CHB-LC)were selected as the CHB-LC group,and 52 patients with hepatitis B-related acute-on-chronic liver failure were selected as the ACLF group.The clinicopathological data of the three groups were collected for retrospective analysis.Peripheral serum HBV DNA of the three groups was collected.The pre-C region genes of HBV in the three groups were amplified by real-time fluorescent quantitative polymerase chain reaction(qRT-PCR),and then gene sequencing was performed.The variation at position 1896 of the pre-C region gene of HBV in the three groups was recorded.The general data,hepatitis B e antigen(HBeAg),HBV DNA quantification,triglycerides(TG),total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),and gene mutation in the pre-C region of the three groups were observed and compared.Logistic regression analysis was performed on the related influencing factors of the onset of hepatitis B-related ACLF.Results There were no statistically significant differences in gender,age,disease course,body mass index(BMI),TG,TC,and BUN among the three groups(all P>0.05),and there were statistically significant differences in HBeAg,HBV DNA quantification,ALT,and AST among the three groups(all P<0.05).The HBV DNA quantification,ALT,and AST in the ACLF group were higher than those in the CHB group and the CHB-LC group(all P<0.05).The mutation rate at position 1896 of the pre-C region gene of HBV in the ACLF group was higher than that in the CHB group and the CHB-LC group(all P<O.05);The results of logistic multivariate regression analysis showed that HBV DNA quantification,ALT,and gene mutation in the pre-C region were independent influencing factors for the onset of hepatitis B-related ACLF(0R=1.042,1.570,1.413,P<0.05).Conclusions The variation at position 1896 of the pre-C region gene of HBV is common in patients with HBV infection at different disease courses.The incidence of its variation shows a gradually increasing trend in CHB,CHB-LC,and ACLF.Elevated HBV DNA and ALT and gene mutation in the pre-C region of HBV are independent risk factors for the occurrence of hepatitis B-related ACLF.The progress of the disease in such patients requires clinical attention.