BCP区和前C区突变检测在慢加急性肝衰竭中的临床价值

Clinical value of BCP region and pre-C region mutation detection in acute-on-chronic liver failure

目的探讨检测乙型肝炎病毒(hepatitis B virus,HBV)相关慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)患者基本核心启动子区(basic core promoter,BCP)A1762T/G1764A和前C区G1896A突变的临床价值。方法选取2010年9月至2020年10月中国科学院大学宁波华美医院收治的403例慢性HBV感染患者,根据患者是否发生ACLF将其分为慢性乙型肝炎(chronic hepititis B,CHB)组(369例)和ACLF组(34例),并根据预后将ACLF组患者再分为缓解组和恶化组。采用多因素Logistic回归分析筛选发生ACLF的独立影响因素,并构建联合预测模型。绘制受试者操作特征曲线以评价该模型的诊断价值。结果ACLF组患者的年龄、总胆红素(total bilirubin,TBiL)、谷草转氨酶、碱性磷酸酶、甲胎蛋白、凝血酶原时间均显著高于CHB组(P<0.05),乙型肝炎e抗原阳性率、白蛋白(albumin,ALB)均显著低于CHB组(P<0.05)。ACLF组和CHB组患者A1762T/G1764A突变率比较差异无统计学意义(P>0.05),ACLF组患者G1896A突变率显著高于CHB患者(P<0.05)。多因素Logistic回归分析结果显示,年龄、TBiL、ALB、G1896A突变均是发生ACLF的独立影响因素(P<0.05)。以上4项指标联合诊断ACLF的曲线下面积为0.950,敏感度和特异性分别为88.24%和93.22%;缓解组和恶化组患者的A1762T/G1764A、G1896A突变率比较差异均无统计学意义(P>0.05)。结论HBV相关ACLF患者的前C区G1896A突变率显著增高是ACLF发病的独立危险因素,而BCP区A1762T/G1764A突变与ACLF发病的关系可能并不紧密。

Objective To investigate the clinical value of mutation detection of A1762T/G1764A in basic core pro-moter(BCP)region and G1896A in pre-C region in acute-on-chronic liver failure(ACLF)patients with hepatitis B virus(HBV).Methods A total of 403 patients with chronic HBV infection who were diagnosed and treated in Hwamei Hospital,University of Chinese Academy of Sciences from September 2010 to October 2020 were selected.The patients were divided into chronic hepatitis B(CHB)group(369 cases)and ACLF group(34 cases)according to whether they developed ACLF or not,and the patients in ACLF group were subdivided into remission group and worsening group according to prognosis.Multivariate Logistic regression analysis was used to screen independent in-fluencing factors of ACLF,and a joint prediction model was constructed.Receiver operating characteristic curves were drawn to evaluate the diagnostic value of the model.Results Age,total bilirubin(TBiL),aspartate transaminase,alkaline phosphatase,alpha fetoprotein,prothrombin time in ACLF group were significantly higher than that in CHB group(P<0.05),and the positive rate of hepatitis B virus e antigen and albumin(ALB)were significantly lower than those in CHB group(P<0.05).There was no significant difference in A1762T/G1764A mutation rate between ACLF group and CHB group(P>0.05).The G1896A mutation rate in ACLF group was significantly higher than that in CHB patients(P<0.05).Multivariate Logistic regression results showed that age,TBiL,ALB,and G1896A mutations were all independent influencing factors of ACLF(P<0.05).The area under the curve of the combined diagnosis of ACLF with the above four indicators was 0.950,and the sensitivity and specificity were 88.24%and 93.22%.There was no significant difference in the A1762T/G1764A and G1896A mutation rates between the remission group and the wor-sening group(P>0.05).Conclusion The mutation rate of G1896A in the pre-C region of patients with HBV-related ACLF was significantly increased,which was an independent risk factor for the onset of ACLF,while the A1762T/G1764A mutation in BCP region may not be closely related to the onset of ACLF.