基线乙型肝炎核心抗体定量与慢加急性肝衰竭患者预后的相关性

Impact of baseline hepatitis B core antibody on prognosis of patients with hepatitis B virus related acute-on-chronic liver failure

目的分析基线乙型肝炎核心抗体定量(qHBcAb)与乙型肝炎病毒(HBV)相关慢加急性肝衰竭(HBV-ACLF)患者预后的相关性,及其对HBV-ACLF预后的预测价值。方法纳入2019年7月1日至2021年12月30日无锡市第五人民医院收治的HBV-ACLF患者91例(HBV-ACLF组),并纳入慢性乙型肝炎(CHB)患者50例(CHB组)及慢性HBV携带状态患者50例(HBV携带组)为对照,收集qHBcAb、血常规、生化、凝血功能、乙型肝炎表面抗原(HBsAg)、乙型肝炎e抗原(HBeAg)、HBV DNA等基线资料,进行回顾性分析。将qHBcAb、HBsAg和HBV DNA数据进行对数转换。采用Cox多因素回归分析qHBcAb水平与生存结局的相关性;随访90 d,用Kaplan-Meier法进行生存分析;用受试者工作特征(ROC)曲线评价qHBcAb对HBV-ACLF患者预后的预测价值。结果HBV-ACLF组基线qHBcAb水平为(4.83±0.42)IU/ml,高于CHB组[(4.59±0.54)IU/ml]及HBV携带组[(3.86±0.74)IU/ml](P均<0.05)。随访90 d后,HBV-ACLF组生存46例(50.5%),死亡45例(49.5%)。生存患者基线qHBcAb水平高于死亡患者[(4.93±0.22)IU/ml比(4.70±0.52)IU/ml,P<0.01]。生存和死亡患者在甲胎蛋白、国际标准化比值、凝血酶原时间、抗凝血酶Ⅲ活性、血小板计数、终末期肝病模型评分、是否合并肝性脑病的差异均有统计学意义(P均<0.05)。Cox多因素回归分析显示基线qHBcAb是患者90 d生存结局的独立影响因素(HR=0.027,95%CI 0.001~0.696,P<0.05)。基线qHBcAb水平预测肝衰竭患者90 d生存结局的ROC曲线下面积为0.639(95%CI 0.525~0.752,P<0.05),截断值为4.89 IU/ml。基线qHBcAb≥4.89 IU/ml患者累积生存率高于基线qHBcAb<4.89 IU/ml患者(P<0.05)。结论基线qHBcAb水平与HBV-ACLF患者的预后相关,可能作为预测HBV-ACLF临床结局的一种新型生物学标志物;当qHBcAb<4.89 IU/ml时,患者病死率较高。

Objective To analyze the impact of baseline quantification of hepatitis B core antibody(qHBcAb)on prognosis of patients with hepatitis B virus(HBV)related acute-on-chronic liver failure(HBV-ACLF).Methods A total of 91 HBV-ACLF patients(HBV-ACLF group),who admitted to Wuxi No.5 People′s Hospital from July 1,2019 to December 30,2021,were included in this study.Fifty chronic hepatitis B(CHB)patients(CHB group)and 50 chronic HBV carriers(HBV carrier group)were enrolled as controls.Baseline clinical data such as qHBcAb,blood routine examination biochemical,and coagulation indices,HBsAg,hepatitis B e antigen(HBeAg),HBV DNA levels were recorded and analyzed retrospectively.The HBV-ACLF,HBsAg and HBV-DNA data were converted logarithmically.Patients were followed-up for 90 days.Cox regression was used to analyze the correlation between HBV-ACLF and survival outcome;survival rate was estimated by the Kaplan-Meier method;receiver operating characteristic(ROC)curve was used to evaluate the predictive value of baseline qHBcAb for the prognosis in patients with HBV-ACLF.Results The baseline qHBcAb level in HBV-ACLF patients was(4.83±0.42)IU/ml,which was significantly higher than that in the CHB group[(4.59±0.54)IU/ml]and chronic HBV carrier group[(3.86±0.74)IU/ml](all P<0.05).At the end of 90 days follow-up,46 patients(50.55%)survived,and 45 patients(49.45%)died in the HBV-ACLF group.The baseline qHBcAb level was significantly higher in the survival group[(4.93±0.22)IU/ml]than in the death group[(4.70±0.52)IU/ml,P<0.01].Significant differences were also found in the alpha fetoprotein,international normalized ratio,prothrombin activity,antithrombinⅢactivity,platelet,end-stage liver disease model score and hepatic encephalopathy complication between the two groups(P<0.05).Cox regression analysis showed that the baseline qHBcAb was an independent risk factor affecting the 90-day survival of HBV-ACLF patients[hazard ratio=0.027,95%confidence interval(CI)0.001-0.696,P<0.05].The area under the ROC curve of baseline qHBcAb level for predicting the 90-day survival outcome of HBV-ACLF patients was 0.639(95%CI 0.525-0.752,P<0.05),with a cut-off value of 4.89 IU/ml.The cumulative survival rate of patients with baseline qHBcAb≥4.89 IU/ml was higher than that of patients with baseline qHBcAb<4.89 IU/ml(P<0.05).Conclusions Higher baseline qHBcAb level is associated with favorable outcome of HBV-ACLF patients and baseline qHBcAb may be used as a new biomarker to predict the clinical outcome of HBV-ACLF patients.HBV-ACLF patients with serum qHBcAb lower than 4.89 IU/ml face increased risk of short-term death.