HBV pgRNA联合HBcrAg对慢性乙型肝炎患者停药后复发的预测价值

Predictive value of HBV pgRNA combined with HBcrAg on the relapse of patients with chronic hepatitis B after drug withdrawal

目的分析乙型肝炎病毒(hepatitis B virus,HBV)前基因组RNA(pregenomic RNA,pgRNA)水平联合HBV核心相关抗原(hepatitis B virus core-related antigen,HBcrAg)定量对慢性乙型肝炎(chronic viral hepatitis B,CHB)患者停药后复发风险的预测价值。方法选取中国人民解放军联勤保障部队第926医院2020年6月至2021年6月收治的113例CHB患者为研究对象,所有患者均已给予足疗程的正规抗病毒治疗,停药前均检测批pgRNA与HBcrAg。根据患者停药1年内复发情况分为复发组(38例)和未复发组(70例),比较两组患者的一般资料、肝功能、肾功能、甲胎蛋白(alphafetoprotein,AFP)、pgRNA及HBcAg水平等指标。应用多因素Logistic回归分析CHB患者停药后复发的影响因素。应用受试者工作特征(receiver operator characteristic,ROC)曲线分析pgRNA联合HBcrAg对CHB患者停药后复发风险的预测价值。结果复发组患者饮酒史比例[47.37%(18/38)比22.86%(16/70)]、AFP[(29.64±7.18)μg/L比(20.38±6.46)μg/L]、pgRNA[(7.97±1.99)lg拷贝/ml比(4.97±1.24)lg拷贝/ml]和HBcrAg[(7.04±1.76)lg IU/ml比(5.11±1.28)lg IU/ml]水平均显著高于未复发组(P均<0.05)。多因素Logistic回归分析表明,饮酒史(OR=5.354,95%CI:1.055~68.858,P=0.046)、AFP(OR=1.189,95%CI:1.036~1.468,P=0.015)、pgRNA(OR=1.047,95%CI:1.117~8.109,P=0.007)和HBcrAg(OR=2.152,95%CI:1.154~4.308,P=0.021)是CHB患者停药后复发的独立危险因素。pgRNA与HBcrAg联合预测CHB患者停药后复发的ROC曲线下面积为0.954,最佳截点为>0.128,此时敏感度为98.9%,特异度为97.1%。结论pgRNA和HBcrAg与CHB患者停药后复发风险密切相关,早期监测两者水平有助于发现停药后复发高风险的患者,早期调整治疗方案。

Objective To analyze the predictive value of hepatitis B virus(HBV)pregenomic RNA(pgRNA)level combined with hepatitis B virus core-related antigen(HBcrAg)quantification on the relapse of patients with chronic viral hepatitis B(CHB)after drug withdrawal.Methods A total of 113 patients with CHB who were treated in the 926th Hospital of the Chinese People’s Liberation Army Joint Logistic Support Force from June 2020 to June 2021 were involved.All patients had received a full course of formal antiviral therapy,pgRNA and HBcrAg were detected before drug withdrawal.Patients were divided into relapse group(38 cases)and non-relapse group(70 cases)according to the recurrence situation within 1 year after drug withdrawal.General data,liver function,renal function,alpha-fetoprotein(AFP),pgRNA and HBcAg of patients in two groups were compared.Multivariate Logistic regression was used to analyze the influencing factors of relapse in patients with CHB after drug withdrawal.Receiver operator characteristic(ROC)curve was used to analyze the value of pgRNA combined with HBcrAg in predicting the relapse in patients with CHB after drug withdrawal.Results The proportion of alcohol consumption history[47.37%(18/38)vs.22.86%(16/70)],AFP[(29.64±7.18)μg/L vs.(20.38±6.46)μg/L],pgRNA[(7.97±1.99)lg copy/ml vs.(4.97±1.24)lg copy/ml]and HBcrAg[(7.04±1.76)lg IU/ml vs.(5.11±1.28)lg IU/ml]of patients in relapse group were significantly higher than those in non-relapse group(all P<0.05).Multivariate Logistic regression analysis showed that alcohol consumption history(OR=5.354,95%CI:1.055~68.858,P=0.046),AFP(OR=1.189,95%CI:1.036~1.468,P=0.015),pgRNA(OR=1.047,95%CI:1.117~8.109,P=0.007)and HBcrAg(OR=2.152,95%CI:1.154~4.308,P=0.021)were independent risk factors for relapse in patients with CHB after drug withdrawal.The area under the ROC curve of pgRNA+HBcrAg for predicting the relapse of patients with CHB after drug withdrawal was 0.954,with an optimal cutoff point>0.128,the sensitivity was 98.9%and the specificity was 97.1%.Conclusions pgRNA and HBcrAg were closely related to the relapse in CHB patients after drug withdrawal.Early monitoring of both levels was helpful to identify high risk of relapse in patients with CHB after drug withdrawal and early adjustment of treatment plan.