肝硬化肝癌和无肝硬化肝癌患者围术期肝衰竭和死亡的相关因素分析

摘要

Objective To investigate the risk factors resulting in the perioperative liver failure and death for the HBV-associated hepatocellular carcinoma (HCC) patients with or without cirrhosis.Methods The method of retrospective case-control study was performed.The clinicopathological data of 1 083 HCC patients with positive HBsAg who received curative liver resection at the Southwest Hospital from January 2008 to December 2012 were collected.According to the absence or presence of cirrhosis,the HCC patients with positive HBsAg were divided into the 2 groups,including the cirrhosis group (633 patients) and the non-cirrhosis group (450patients).The intraoperative conditions (operation time,volume of intraoperative blood loss,rate of blood transfusion,rate of pringle maneuver) and postoperative conditions (incidence of perioperative complications,duration of postoperative hospital stay,perioperative mortality) of HCC patients were observed.The gender,age,alanine transaminase (ALT),aspartate transaminase (AST),albumin (Alb),total bilirubin (TBil),platelet (PLT),Child-Pugh classification,operation time,volume of intraoperative blood loss,blood transfusion,pringle maneuver,extent of liver resection,number of tumors,tumor diameter,tumor thrombus and liver cirrhosis were enrolled and prognostic factors resulting in perioperative liver failure and death for the HCC patients were explored.Measurement data with skewed distribution were presented as M (range) and comparison between the 2 groups was analyzed using Mann-Whitney U test.Count data were presented as counts (percentage) and comparison between the 2 groups was analyzed using chi-square test or Fisher exact probability.Univariate analysis was performed by chi-square test and multivariate analysis was performed by Logistic regression model (forward).Results (1) The intraoperative conditions:the volume of intraoperative blood loss were 500 mL (range,30-7 000 mL) in the cirrhosis group and 400 mL (range,50-8 000 mL) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (Z =-2.209,P ＜ 0.05).The operation time,rate of blood transfusion and rate of pringle maneuver were 250 minutes (range,82-715 minutes),29.86％ (189/633),62.24％ (394/633) in the cirrhosis group and 242 minutes (range,85-738 minutes),27.11％ (122/450),66.67％ (300/450) in the non-cirrhosis group,respectively,with no statistical differences between the 2 groups (Z =-1.212,x2 =0.969,2.236,P ＞0.05).(2) The postoperative conditions:the incidence of perioperative complications was 30.49％(193/633) in the cirrhosis group and 21.11％ (95/450) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (x2 =11.851,P ＜ 0.05).The incidence of lung infection,abdominal infection and liver failure were 6.48％ (41/633),2.69％ (17/633),5.53％ (35/633) in the cirrhosis group and 3.56％ (16/450),0.89％ (4/450),1.33％ (6/450) in the non-cirrhosis group,respectively,with statistically significant differences between the 2 groups (x2 =4.502,4.465,12.713,P ＜ 0.05).The duration of postoperative hospital stay was 15 days (range,0-70 days) in the cirrhosis group and 14 days (range,0-71 days) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (Z =-3.448,P ＜ 0.05).The perioperative mortality was 5.85％ (37/633) in the cirrhosis group and 2.44％ (11/450) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (x2=7.181,P ＜ 0.05).(3)Results of risk factors affecting perioperative liver failure:①results of univariate analysis showed that age,AST,Alb,Child-Pugh classification,operation time,volume of intraoperative blood loss,blood transfusion,extent of liver resection,tumor diameter,liver cirrhosis with positive HBsAg were associated with perioperative liver failure in HCC patients (x2=5.013,7.979,8.855,16.968,14.148,9.764,18.511,11.749,5.534,12.713,P＜0.05);age,AST,Alb,Child-Pugh classification,operation time,blood transfusion,extent of liver resection and tumor diameter were associated with perioperative liver failure in the cirrhosis group (x2=5.877,5.380,11.087,13.672,8.849,13.170,12.418,5.805,P ＜ 0.05);volume of intraoperative blood loss was associated with perioperative liver failure in the non-cirrhosis group (P ＜ 0.05).②Results of multivariate analysis showed that age≥60 years,Child-Pugh class B,operation time ＞ 360 minutes,blood transfusion,extent of liver resection ≥3 segments and liver cirrhosis were independent risk factors affecting perioperative liver failure in HCC patients with positive HBsAg [OR =2.285,2.716,2.315,2.159,2.459,4.322;95％ confidence interval (CI):1.081-4.831,1.100-6.706,1.064-5.038,1.068-4.362,1.264-9.786,1.763-10.598,P＜0.05];Alb ＜38 g/L,Child-Pugh class B,blood transfusion and extent of liver resection ≥ 3 segments were independent risk factors affecting perioperative liver failure in the cirrhosis group (OR =2.231,2.857,2.186,2.927,95％ CI:1.038-4.795,1.095-7.451,1.045-4.576,1.426-6.008,P ＜ 0.05);volume of intraoperative blood loss ＞ 1 200 mL was an independent risk factor affecting perioperative liver failure in the non-cirrhosis group (OR =15.077,95％CI:2.695-84.353,P ＜ 0.05).(4) Risk factors affecting perioperative death:①results of univariate analysis showed that gender,Alb,TBil,Child-Pugh classification,blood transfusion,extent of liver resection,tumor diameter,tumor thrombus and liver cirrhosis were associated with perioperative death in HCC patients with positive H BsAg (x2=4.462,8.783,4.212,4.869,7.189,11.745,6.837,4.323,7.181,P ＜0.05);Alb,extent of liver resection and tumor diameter were associated with perioperative death in the cirrhosis group (x2=12.173,12.793,10.981,P ＜ 0.05);blood transfusion and tumor thrombus were associated with perioperative death in the non-cirrhosis group (x2 =5.836,6.417,P ＜ 0.05).② Results of multivariate analysis showed that Alb ＜38 g/L,extent of liver resection ≥ 3 segments and liver cirrhosis were independent risk factors affecting perioperative death in HCC patients with positive HBsAg (OR =2.560,2.657,2.567,95％ CI:1.382-4.742,1.471-4.800,1.283-5.134,P ＜ 0.05);Alb ＜ 38 g/L,extent of liver resection ≥ 3 segments and tumor diameter≥5 cm were independent risk factors affecting perioperative death in the cirrhosis group (OR =3.003,2.533,3.060,95％ CI:1.495-6.034,1.251-5.128,1.135-8.251,P＜0.05);blood transfusion and tumor thrombus were independent risk factors affecting perioperative death in the non-cirrhosis group (OR =3.755,4.036,95％ CI:1.047-13.467,1.126-14.469,P ＜ 0.05).Conclusions Liver cirrhosis is an independent risk factor for perioperative liver failure and death in HCC patients with positive HBsAg.The risk of perioperative liver failure and death in HCC patients with cirrhosis is significantly higher than that in HCC patients without cirrhosis,and there is a difference in the risk factors for perioperative liver failure and death.%目的 探讨乙型病毒性肝炎相关的肝硬化肝癌和无肝硬化肝癌患者围术期肝衰竭和死亡的危险因素.方法 采用回顾性病例对照研究方法.收集2008年1月至2012年12月第三军医大学西南医院1 083例行肝癌切除术的HBsAg阳性患者的临床病理资料.根据术后病理学检查结果证实有无肝硬化,将633例合并肝硬化的HBsAg阳性肝癌患者设为肝硬化组,450例无肝硬化的HBsAg阳性肝癌患者设为无肝硬化组.观察指标:(1)术中情况:手术时间、术中出血量、输血率、肝门阻断率.(2)术后情况:围术期并发症发生率、术后住院时间、围术期病死率.(3)纳入患者性别、年龄、ALT、AST、Alb、TBil、PLT、ChildPugh分级、手术时间、术中出血量、输血、肝门阻断、肝切除范围、肿瘤数目、肿瘤直径、癌栓、肝硬化指标,分析影响HBsAg阳性肝癌患者围术期肝衰竭和死亡的危险因素.采用门诊和电话方式进行随访,复查相关实验室和影像学检查.随访时间截至2014年9月.偏态分布的计量资料用M(范围)表示,两组比较采用Mann-Whitney U检验.计数资料用例数(百分比)表示,两组比较采用x2检验或Fisher确切概率法.单因素分析采用x2检验,多因素分析采用Logistic回归模型(前进法).结果 (1)术中情况:肝硬化组患者术中出血量为500 mL(30 ～7 000 mL),无肝硬化组患者术中出血量为400 mL(50 ～8 000 mL),两组比较,差异有统计学意义(Z=-2.209,P＜0.05).肝硬化组患者手术时间、输血率、肝门阻断率分别为250 min(82～715 min)、29.86％(189/633)、62.24％(394/633),无肝硬化组患者上述指标分别为242 min(85～738 min)、27.11％ (122/450)、66.67％(300/450),两组比较,差异无统计学意义(Z=-1.212,x2=0.969,2.236,P＞0.05).(2)术后情况:肝硬化组患者围术期并发症发生率为30.49％(193/633),无肝硬化组患者围术期并发症发生率为21.11％ (95/450),两组比较,差异有统计学意义(x2=11.851,P＜0.05).其中肝硬化组患者肺部感染、腹腔感染、肝衰竭发生率分别为6.48％ (41/633)、2.69％(17/633)、5.53％(35/633),无肝硬化组上述指标分别为3.56％ (16/450)、0.89％ (4/450)、1.33％ (6/450),两组比较,差异有统计学意义(x2=4.502,4.465,12.713,P＜0.05).肝硬化组患者的术后住院时间为15 d(0 ～70 d),无肝硬化组患者的术后住院时间为14 d(0 ～71 d),两组比较,差异有统计学意义(Z=-3.448,P＜0.05).肝硬化组患者和无肝硬化组患者围术期病死率分别为5.85％(37/633)和2.44％(11/450),两组比较,差异有统计学意义(x2=7.181,P＜0.05).(3)影响围术期肝衰竭的危险因素分析结果:①单因素分析结果显示:年龄、AST、Alb、Child-Pugh分级、手术时间、术中出血量、输血、肝切除范围、肿瘤直径、肝硬化与HBsAg阳性肝癌患者围术期肝衰竭相关(x2=5.013,7.979,8.855,16.968,14.148,9.764,18.511,11.749,5.534,12.713,P＜0.05);年龄、AST、Alb、Child-Pugh分级、手术时间、输血、肝切除范围、肿瘤直径与肝硬化组患者围术期肝衰竭相关(x2=5.877,5.380,11.087,13.672,8.849,13.170,12.418,5.805,P＜0.05);术中出血量与无肝硬化组患者围术期肝衰竭相关(P＜0.05).②多因素分析结果显示:年龄≥60岁、ChildPugh分级为B级、手术时间＞360 min、输血、肝切除范围≥3段、肝硬化是HBsAg阳性肝癌患者围术期发生肝衰竭的独立危险因素(OR=2.285,2.716,2.315,2.159,2.459,4.322,95％可信区间:1.081 ～4.831,1.100～6.706,1.064～5.038,1.068 ～4.362,1.264～4.786,1.763 ～ 10.598,P＜0.05);Alb ＜38 g/L、ChildPugh分级为B级、输血、肝切除范围≥3段是肝硬化组患者围术期发生肝衰竭的独立危险因素(OR=2.231,2.857,2.186,2.927,95％可信区间:1.038 ～4.795,1.095～7.451,1.045 ～4.576,1.426 ～6.008,P＜0.05);术中出血量＞1 200 mL是无肝硬化组患者围术期发生肝衰竭的独立危险因素(OR=15.077,95％可信区间:2.695 ～ 84.353,P＜0.05).(4)影响围术期死亡的危险因素分析结果:①单因素分析结果显示:性别、Alb、TBil、Child-Pugh分级、输血、肝切除范围、肿瘤直径、癌栓、肝硬化与HBsAg阳性肝癌患者围术期死亡相关(x2=4.462,8.783,4.212,4.869,7.189,11.745,6.837,4.323,7.181,P＜0.05);Alb、肝切除范围、肿瘤直径与肝硬化组患者围术期死亡相关(x2=12.173,12.793,10.981,P＜0.05);输血、癌栓与无肝硬化组患者围术期死亡相关(x2=5.836,6.417,P＜0.05).②多因素分析结果显示:Alb＜ 38 g/L、肝切除范围≥3段、肝硬化是HBsAg阳性肝癌患者围术期死亡的独立危险因素(OR=2.560,2.657,2.567,95％可信区间:1.382 ～4.742,1.471 ～4.800,1.283 ～5.134,P＜0.05);Alb＜ 38 g/L、肝切除范围≥3段、肿瘤直径≥5 cm是肝硬化组患者围术期死亡的独立危险因素(OR=3.003,2.533,3.060,95％可信区间:1.495～6.034,1.251～5.128,1.135～8.251,P ＜0.05);输血、癌栓是无肝硬化组患者围术期死亡的独立危险因素(OR=3.755,4.036,95％可信区间:1.047 ～ 13.467,1.126 ～ 14.469,P＜0.05).结论 肝硬化是影响HBsAg阳性肝癌患者围术期肝衰竭和死亡的独立危险因素.肝硬化肝癌患者出现围术期肝衰竭和死亡的风险明显高于肝癌无肝硬化患者,并且影响其围术期肝衰竭和死亡的危险因素也不相同.