熊去氧胆酸减轻移植肝缺血再灌注损伤的临床前瞻性随机对照研究

目的 探讨熊去氧胆酸(UDCA)减轻移植肝缺血再灌注损伤(IRI)的临床效果.方法 将80例终末期肝病成人患者随机分为两组,一组42例,肝移植术后第1天起给予UDCA 10～15 mg·kg-1·d-1,维持治疗3个月,为UDCA组;另一组38例肝移植患者不使用UDCA,作为对照.分析两组术后3周内的肝生化指标、"严重IRI致移植物功能恢复延迟"、急性细胞性排斥反应(ACR)及药物性肝损伤的发生情况,以及术后3个月内血管及胆管并发症、患者死亡率、病毒性肝炎和原发性肝病复发情况.结果 UDCA组供肝热缺血时间和冷缺血时间分别为(3.33±0.92)min和(10.3±1.9)h,对照组分别为(3.68±1.16)min和(9.8±2.4)h,两组间的差异无统计学意义.UDCA组术后第7、14及21天的血清丙氨酸转氨酶显著低于对照组(P＜0.05),第7天的天冬氨酸转氨酶(AST)和γ-谷氨酰转移酶(γ-GT)也显著低于对照组(P＜0.05);两组其它时段AST、γ-GT及各时段胆红素总量、直接胆红素及碱性磷酸酶水平的差异均无统计学意义.UDCA组"严重IRI致移植物功能恢复延迟"发生率为9.5%(4/42),对照组为26.3%(10/38),两组比较,差异有统计学意义(P＜0.05).两组术后3周内ACR发生率和严重程度、药物性肝损伤发生率及术后3个月内胆管和血管并发症发生率的差异无统计学意义,患者死亡率的差异也无统计学意义.结论 UDCA可有效减轻移植肝的缺血再灌注损伤,降低"严重IRI致移植物功能恢复延迟"的发生率;但在冷缺血时间＜12 h的情况下,未能显示出保护胆管的临床效果.

A prospective, randomized, controlled clinical trial of the effects of ursodeoxycholic acid alleviating ischemia/reperfusion injury in liver transplantation

Objective To investigate the effects of ursodeoxycholic acid(UDCA)alleviating ischemia/reperfusion injury(IRI)in liver transplantation. Methods Eighty adult patients with endstage liver diseases were randomly divided into two groups:UIXTA group(n=42)in which UDCA 38)in which UDCA was not administered.The two groups were statistically compared in liver biochemical parameters,rate of severe IRI-induced graft dysfunction,acute cellular rejection(ACR)episodes,drug-induced hepatotoxicity,viral hepatitis and recurrence of primary liver disease within posttransplant 3 weeks as well as rate of vascular,biliary complications and death within post-transplant 3 months.Results Warm ischemia time(WIT)and cold ischemia time(CIT)in UDCA group were respectively(3.33±0.92)min and(10.3±1.9)h,and those in control group were(3.68±1.16)min and(9.8±2.4)h.There were no significant differences in these two parameters between the two groups.In UDCA group,serum ALT levels on post-transplant day 7,14,21 were significantly lower than those in control group(P＜0.05),and compared with control group,serum levels of AST and γ-GT on day 7 were also lower in UDCA group(P＜0.05).The cases of severe IRI-induced graft dysfunction in UDCA group were fewer than those in control group with the difference being significant (9.5 % vs. 26.3 %,P＜0.05).There were no significant difference between the two groups in rate of ACR episode,drug-induced hepatotoxicity within post-transplant 3 weeks as well as rate of vascu lar,biliary complications and death within post-transplant 3 months.Conclusion UDCA treatment can alleviate graft IRI early after liver transplantation. It significantly decreased incidence of severe IRI-induced graft dysfunction.Protective effects of bile duct by UIX2A were not shown when CIT was beneath 12 h.