人工肝多模式序贯联合治疗乙型肝炎病毒相关慢加急性肝衰竭患者的近期疗效观察

Therapeutic effect of artificial liver multi-mode sequential combination in patients with hepatitis B virus-related acute-on-chronic liver failure

目的探索人工肝多模式序贯联合治疗乙型肝炎病毒相关慢加急性肝衰竭(hepatitis B virus-related acute-on-chronic liver failure,HBV-ACLF)患者的疗效。方法回顾性分析2018年1月至2021年6月于无锡市第五人民医院经人工肝治疗的HBV-ACLF住院患者临床资料,将86例患者分为人工肝多模式序贯联合治疗组(简称序贯联合组)和常规治疗组,分析病程14 d两组细胞因子水平变化和终末期肝病模型(model for end-stage liver disease,MELD)评分,随访30 d分析患者预后及人工肝并发症情况。统计学比较采用两独立样本t检验和χ^(2)检验,Cox回归分析患者死亡的危险因素,Kaplan-Meier法分析患者的生存情况。结果86例患者中序贯联合组48例,平均人工肝次数为4.68次/人;常规治疗组38例,平均人工肝次数为3.17次/人。病程14 d后序贯联合组患者白细胞介素(interleukin,IL)6、IL-8、γ干扰素诱导蛋白(interferonγ-inducible protein,IP)-10水平及MELD评分下降幅度均大于常规治疗组,差异均有统计学意义(t=3.80、3.62、4.95、1.11,均P<0.050)。随访30 d,患者生存63例,死亡23例。Cox回归分析提示基线国际标准化比值[风险比(hazard ratio,HR)=0.558,95%可信区间(confidence interval,CI)0.193~0.856,P=0.027]、基线抗凝血酶Ⅲ活性(HR=0.876,95%CI 0.824~0.932,P<0.001)、人工肝治疗模式(HR=0.819,95%CI 0.236~0.992,P=0.005)、自发性腹膜炎(HR=0.170,95%CI 0.045~0.647,P=0.009)、肝性脑病(HR=0.004,95%CI 0.001~0.030,P<0.001)是影响患者30 d生存结局的独立影响因素。序贯联合组累积生存率高于常规治疗组,差异有统计学意义(χ^(2)=5.45,P=0.020)。两组患者发生出血、深静脉血栓及心率血压不稳定的比例差异均无统计学意义(χ^(2)=0.63、1.20、0.54,均P>0.050),序贯联合组患者血小板计数下降幅度小于常规治疗组,差异有统计学意义(t=-4.17,P=0.002)。结论人工肝多模式序贯联合治疗HBV-ACLF患者可以更有效地清除细胞因子和降低MELD评分,延长患者生存期,并且对血小板计数影响较小。

Objective To explore the therapeutic effect of multi-mode sequential combination of artificial liver in the treatment of hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).Methods The clinical data of HBV-ACLF patients treated with artificial liver in Wuxi Fifth People′s Hospital from January 2018 to June 2021 were retrospectively analyzed.Eighty-six patients were divided into artificial liver multi-mode sequential combination therapy group(sequential combination group)and conventional treatment group.The cytokine level changes and model for end-stage liver disease(MELD)score were analyzed at 14 days of disease duration.The survival outcome and complications of artificial liver were analyzed after 30 days of follow-up.Two independent samples t test and chi-square test were used for statistical analysis.Cox regression analysis was used to analyze the risk factors of death,and Kaplan-Meier method was used to analyze the survival rate of patients.Results A total of 86 patients were enrolled,including 48 patients in sequential combination group with the average number of artificial liver of 4.68 times/person,and 38 patients in conventional treatment group with the average number of artificial liver of 3.17 times/person.At 14 days of disease duration,interleukin(IL)-6,IL-8,interferonγ-inducible protein(IP)-10 level and MELD score in sequential combination group decreased significantly than those in the conventional treatment group(t=3.80,3.62,4.95 and 1.11,respectively,all P<0.050).After 30 days of follow-up,63 patients survived and 23 patients died.Cox regression analysis showed that baseline international normalized ratio(hazard ratio(HR)=0.558,95%confidence interval(CI)0.193 to 0.856,P=0.027),baseline antithrombinⅢactivity(HR=0.876,95%CI 0.824 to 0.932,P<0.001),artificial liver mode(HR=0.819,95%CI 0.236 to 0.992,P=0.005),spontaneous peritonitis(HR=0.170,95%CI 0.045 to 0.647,P=0.009)and hepatic encephalopathy(HR=0.004,95%CI 0.001 to 0.030,P<0.001)were independent influencing factors for 30-day survival outcome.The cumulative survival rate of sequential combination group was higher than that of conventional treatment group,and the difference was statistically significant(χ^(2)=5.45,P=0.020).There were no significant differences in the proportions of bleeding,deep vein thrombosis,heart rate and blood pressure instability between the two groups(χ^(2)=0.63,1.20 and 0.54,respectively,all P>0.050).The platelet decline of patients in sequential combination group was slighter than that in conventional treatment group,and the difference was statistically significant(t=-4.17,P=0.002).Conclusions Multi-mode sequential combination therapy of artificial liver could eliminate cytokines and reduce MELD score more effectively in patients with HBV-ACLF,and prolong the survival time of patients and have little effect on platelet count.