乙型肝炎病毒相关慢加急性肝衰竭患者器官功能衰竭的特点与预后

Study on characteristics and prognosis of organ failure in patients with hepatitis B virus-associated acute-on-chronic liver failure

目的应用慢性肝衰竭-序贯器官功能评估（CLIF-SOFA）评分评估我国乙型肝炎病毒相关慢加急性肝衰竭（HBV-ACLF）患者器官衰竭的发生率、器官衰竭的特点及其与预后的关系，更好地指导临床治疗和预后判断。方法回顾性分析316例2015年2月至2016年2月住院期间诊断为HBV-ACLF患者的临床资料，根据CLIF-SOFA评分评估患者有无肝内和肝外器官衰竭，分析其临床特点及其与预后的关系。连续性变量用方差分析或KruskalWallisH检验、分类变量资料的比较应用x2或Fisher精确检验，用受试者工作特征曲线下面积（AUROC）和z检验比较各种预后评分的预测效能。结果316例HBV-ACLF患者的年龄为（45±11）岁，男性占87．3％。78．8％的患者基础肝病为乙型肝炎肝硬化。患者28d、90d和180d无肝移植病死率分别为20．5％（63／307）、36．7％（110／300）和39．2％（116／296）。根据CLIF-SOFA评分，89．9％的患者（284例）在基线时有器官衰竭，其中97．5％的患者有肝脏衰竭（总胆红素≥12mg／d1），只有2．5％患者在无肝脏衰竭的情况下出现了凝血、肾脏、循环或呼吸衰竭。除肝脏器官衰竭外，肝外器官衰竭的发生率依次是凝血（23．1％）、肾脏（5．7％）、脑（3．8％）、循环（1．3％）和呼吸（0．3％）。随着器官衰竭数量的增加，患者的病死率也逐渐增加，2个和3个及3个以上器官衰竭患者90d病死率分别为69．6％和69．2％，显著高于单个器官衰竭和无器官衰竭的患者（分别为27％和6．9％，P〈0．001）。肝脏衰竭合并凝血衰竭（国际标准化比值≥2．5或血小板计数≤20×10^9／L）的患者预后最差，90d病死率高达75％。结论根据CLIF-SOFA评分，我国HBV-ACLF患者主要的器官功能衰竭是肝脏衰竭，2个及以上器官衰竭的患者3个月病死率高达70％，需及时考虑肝移植。

Objective To evaluate the incidence, and the characteristics of organ failure in relationship to prognosis in hepatitis B virus-associated acute-on-chronic liver failure （HBV-ACLF） patients using chronic liver failure-sequential organ failure assessment （CLIF-SOFA） score for judgments of clinical treatment and prognosis. Methods Clinical data of 316 patients who were diagnosed as HBV-ACLF during hospitalization from February 2015 to February 2016 were retrospectively analyzed. Intrahepatic and extrahepatic organ failures were assessed according to CLIF-SOFA score, and the relationship between clinical characteristics and prognosis was analyzed. Continuity variables were analyzed by analysis of variance, or Kmskal-Wallis H test. Comparison of the categorical data were done usingZ 2 or Fisher＇s exact test, and the predictive efficacy of various prognostic scores was compared using the area under the receiver operating characteristic curve （AUROC） and Z-test. Results Of 316 cases （87.3% men） of HBV-ACLF, the mean age was （45 ± 11） years old. 78.8% of patients with underlying liver disease had hepatitis B virus induced cirrhosis. Mortality rates in patients without liver transplantation at 28 days, 90 days and 180 days were 20.5% （63/307）, 36.7% （110/300） and 39.2% （116/296）, respectively. According to the CLIF-SOFA score, 89.9% （284 patients） had organ failure at baseline, of which 97.5% had liver failure （Total bilirubin ≥12 mg/dl） and only 2.5% had coagulation, kidney, circulation or respiratory failure without liver failure. Besides liver failure, the incidence of extrahepatic organ failure was coagulation （23.1%）, kidney （5.7%）, brain （3.8%）, circulation （1.3%） and respiratory failure （0.3%）. With increasing number of organ failure, the mortality rate of two and three or more organ failures were 69.6% and 69.2%, respectively, which was significantly higher than that of single organ failure and non-organ failure patients （27% and 6.9%, respectively; P 〈 0.001）. Liver failure with coagulation failure （International normalized ratio 〉/2.5 or platelet count ≤ 20×10^9/L） had worst prognosis with a mortality rate of up to 75% at 90 days. Conclusion According to the CLIF-SOFA score, the main organ failure in patients with HBV- ACLF in China is liver failure. The mortality rate in patients with two or more organ failures is as high as 70% within 3 months. Therefore, timely manner liver transplantation should be considered.