乙肝相关慢加急性肝衰竭患者肝移植术后影响生存的危险因素分析

Risk factors of short-term mortality after liver transplantation for hepatitis B-related acute-on-chronic liver failure

目的探讨影响乙肝相关慢加急性肝衰竭患者实施肝移植后短期病死率与长期生存的危险因素。方法本研究通过前瞻性收集自2018年8月—2021年7月在首都医科大学附属北京佑安医院因乙肝相关慢加急性肝衰竭实施肝移植的患者40例,其中男性36例、女性4例,年龄为(44.5±8.79)岁。统计患者的基本资料、发病情况、肝移植前48 h内的肝肾功能、血常规、凝血功能、乳酸、感染指标等以及MELD评分、MELD-Na评分、CLIF-C ACLFs评分、CLIF OFs评分、CLIF分级等指标,观察术后90 d内死亡及长期生存情况,并根据肝移植术后3个月内存活情况,分为存活组(n=34)与死亡组(n=6)。符合正态分布的计量资料采用均数±标准差(±s)表示,组间比较采用t检验;偏态分布的计量资料采用M(Q_(1),Q_(3))表示,组间比较采用秩和检验。计数资料采用χ^(2)检验或Fisher确切概率法检验值。通过单因素与多因素分析方法以及生存分析,发现影响肝移植术后短期死亡与长期存活的危险因素,并利用ROC曲线计算敏感度与特异度以及cut-off值。以CLIF-C ACLFs评分48.5分为临界值,把患者分为≥48.5分组(n=10)与<48.5分组(n=30),采用Kaplan-Meier进行生存分析比较。结果40例患者肝移植前48 h内的总胆红素、肌酐、血小板计数、国际标准化比值、乳酸、中性粒细胞/淋巴细胞比值(NLR)分别为24.30(13.45,33.95)mg/dL、0.68(0.53,1.11)mg/dL、56(39,82)×109/L、3.12(2.33,4.46)、2.14(1.59,4.14)mmol/L、4.06(2.12,9.13),MELD、MELD-Na、CLIF OFs、CLIF-C ACLFs、AARC评分分别是(32.1±6.3)、(33.2±5.3)、(11.2±2.6)、(43.8±8.8)、(10.6±2.4)分。在40例患者中,有26例患者并发了肝性脑病,17例患者移植前存在可以控制的全身感染,10例患者合并肾功能损伤,6例患者行呼吸机辅助通气(气管插管),2例患者合并上消化道出血。40例患者均实施了紧急的同种异体原位肝移植术,术后并发症的发生率为47.5%,最常见的为移植后感染(27.5%),其次为肾功能不全(17.5%)。肝移植术后3个月内共有6例患者死亡,病死率为14.5%。存活组与死亡组的移植前临床资料比较,显示两组患者在中性粒细胞淋巴细胞比值(NLR)、乳酸、MELD评分、MELD-Na评分、CLIF-C ACLFs评分、CLIF OF评分、CLIF分级、肝性脑病、感染、肾功能损伤等均有显著差异(P<0.05)。单因素Logistic回归分析显示,肝移植前48 h内的NLR、MELD-Na评分、CLIF-C ACLFs评分、CLIF OF评分是影响肝移植术后短期死亡的危险因素(P<0.05),进一步多因素回归分析显示,CLIF-C ACLFs评分是影响肝移植术后3个月病死率的独立危险因素。采用ROC曲线显示,CLIF-C ACLFs评分的曲线下面积为0.895(95%CI:0.779~1.000,P=0.002),cut-off值为48.5分时诊断敏感度和特异度最高,分别为83.3%和85.3%。同时,CLIF-C ACLFs评分≥48.5分组与<48.5分组的生存分析比较,显示两组在长期生存率上有显著差异(P=0.001)。结论移植前48 h内的NLR、MELD-Na评分、CLIF-C ACLFs评分、CLIF OF评分是影响乙肝相关慢加急性肝衰竭患者实施肝移植术后短期死亡的危险因素,而CLIF-C ACLFs评分是乙肝相关慢加急性肝衰竭患者实施肝移植术后3个月病死率和长期生存的独立危险因素。

Objective To investigate the risk factors for short-term mortality and long-term survival after liver transplantation in patients with hepatitis B related acute-on-chronic liver failure.Methods Forty patients with hepatitis B related acute-on-chronic liver failure performing liver transplantation were prospectively collected from August 2018 to July 2021 in Beijing YouAn Hospital of Capital Medical University.The mean age was(44.5±8.79)years,there were 36 males and 4 females.The basic data,including liver and kidney function,blood routine,coagulation function,lactic acid,infection indexes as well as MELD score,MELD-Na score,CLIF-C ACLFs score,CLIF OFs score,CLIF grade within 48 hours before liver transplantation were counted.The post-LT mortality within 90 days and long-term survival were observed for these patients who were divided into survival group(n=34)and death group(n=6)according to the survival in 3 months after liver transplantation.The measurement data conforming to the normal distribution were expressed by mean±standard deviation(±s),and the comparison was performed by t-test between groups;The skewness data were expressed by M(Q1,Q3),and the rank sum test was used for inter-group comparison.The counting data were tested by Chi square test or Fisher exact probability method.The risk factors of short-term mortality and long-term survival were analyzed through univariate and multivariate analysis as well as survival analysis.The sensitivity,specificity and cut off value were calculated by ROC curve.The patients were divided into≥48.5 scores group(n=10)and<48.5 scores group(n=30)by CLIF-C ACLFs score 48.5 as cut-off value.Kaplan Meier was used for survival analysis and comparison.Results The total bilirubin(TBIL),creatinine(CR),platelet count,international normalized ratio(INR),lactic acid and neutrophil/lymphocyte ratio(NLR)within 48 hours before liver transplantation were 24.30(13.45,33.95)mg/dL,0.68(0.53,1.11)mg/dL and 56(39,82)×109/L,3.12(2.33,4.46),2.14(1.59,4.14)mmol/L,4.06(2.12,9.13)for all forty patients,respectively.The mean MELD,MELD Na,CLIF OFs,CLIF-C ACLFs and AARC scores within 48 hours before transplantation were(32.1±6.3),(33.2±5.3),(11.2±2.6),(43.8±8.8)and(10.6±2.4)scores,respectively.65%of patients were complicated with hepatic encephalopathy,17 patients with controllable systemic infection,10 patients with renal function injury,2 patients with variceal bleeding and 6 patients underwent ventilator-assisted ventilation(endotracheal intubation).All 40 patients underwent emergency orthotopic liver transplantation.The incidence of postoperative complications was 47.5%,the most common was post-LT infection(27.5%),followed by renal insufficiency(17.5%).There were significant differences in neutrophil lymphocyte ratio(NLR),lactic acid,MELD score,MELD Na score,CLIF-C ACLFs score,CLIF OFs score,CLIF grades,hepatic encephalopathy,infection and renal injury between survival group and death group(P<0.05).Univariate logistic regression analysis showed that NLR,MELD Na score,CLIF-C ACLFs score and CLIF OFs score were the risk factors for short-term mortality after liver transplantation(P<0.05).Multivariate logistic regression analysis showed that CLIF-C ACLFs score was an independent risk factor for 3-month mortality after liver transplantation.ROC curve showed that the area under the curve of CLIF-C ACLFs score was 0.895(95%CI:0.779-1.000,P=0.002),and the diagnostic sensitivity and specificity were the highest,83.3%and 85.3%respectively when cut off value was 48.5.Meanwhile,there was significant difference in long-term survival between the patients with CLIF-C ACLFs score≥48.5 and<48.5(P=0.001).Conclusions NLR,MELD Na score,CLIF-C ACLFs score and CLIF OFs score within 48 hours before liver transplantation are the risk factors for short-term mortality after liver transplantation,however CLIF-C ACLFs score is an independent risk factor for three-months mortality and long-term survival in patients with hepatitis B related acute-on-chronic liver failure after liver transplantation.