Ghobrial R M, Farmer D G, Baquerizo A, Colquhoun S, Rosen H R, Yersiz H, Markmann J F, Drazan K E, Holt C, Imagawa D, Goldstein L I, Martin P, Busuttil R W
Dumont-UCLA Liver Transplant Center, Department of Surgery, UCLA School of Medicine, Los Angeles, California 90095, USA.
Ann Surg. 1999 Jun;229(6):824-31; discussion 831-3. doi: 10.1097/00000658-199906000-00009.
To determine the outcome of orthotopic liver transplantation (OLT) for end-stage liver disease caused by hepatitis C virus (HCV).
HCV has become the leading cause of cirrhosis and hepatic failure leading to OLT. Recurrent HCV after OLT is associated with significant complications and may lead to graft loss that requires retransplantation (re-OLT). The authors studied the outcome of transplantation for HCV, the effect of primary immunotherapy, and causes of retransplantation.
The authors conducted a retrospective review of their experience during an 8-year period (1990-1997), during which 374 patients underwent transplants for HCV (298 [79.6%] received one OLT; 76 [20.4%] required re-OLT). Median follow-up was 2 years (range 0 to 8.3). Immunosuppression was based on cyclosporine in 190 patients and tacrolimus in 132 patients. In a third group of patients, therapy was switched from cyclosporine to tacrolimus or from tacrolimus to cyclosporine (cyclosporine/tacrolimus group).
Overall, 1-, 2-, and 5-year actuarial patient survival rates were 86%, 82%, and 76%, respectively. The 2-year patient survival rate was 81 % in the cyclosporine group, 85% in the tacrolimus group, and 82% in the cyclosporine/tacrolimus group. In patients receiving one OLT, overall 1-, 2-, and 5-year patient survival rates were 85%, 81%, and 75%, respectively. The 2-year patient survival rate was 79% in the cyclosporine group, 84% in the tacrolimus group, and 80% in the cyclosporine/tacrolimus group. The overall graft survival rates were 70%, 65%, and 60% at 1, 2, and 5 years, respectively. The graft survival rate at 2 years was similar under cyclosporine (68.5%), tacrolimus (64%), or cyclosporine/tacrolimus (60%) therapy. Re-OLT was required in 42 (11.2%) patients for graft dysfunction in the initial 30 days after OLT. Other causes for re-OLT included hepatic artery thrombosis in 10 (2.6%), chronic rejection in 8 (2.1%), and recurrent HCV in 13 (3.4%) patients. The overall survival rates after re-OLT were 63% and 58% at 1 and 2 years. The 1-year survival rate after re-OLT was 61 % for graft dysfunction, 50% for chronic rejection, 60% for hepatic artery thrombosis, and 60% for recurrent HCV. At re-OLT, 85.3% of the patients were critically ill (United Network for Organ Sharing [UNOS] status 1); only 14.7% of the patients were UNOS status 2 and 3. In re-OLT for chronic rejection and recurrent HCV, the 1-year survival rate of UNOS 1 patients was 38.4%, compared with 87.5% for UNOS 2 and 3 patients. In patients requiring re-OLT, there was no difference in the 1-year patient survival rate after re-OLT when cyclosporine (60%), tacrolimus (63%), or cyclosporine/tacrolimus (56%) was used for primary therapy. With cyclosporine, three patients (1.5%) required re-OLT for chronic rejection versus one patient (0.7%) with tacrolimus. Re-OLT for recurrent HCV was required in four (3%) and seven (3.6%) patients with tacrolimus and cyclosporine therapy, respectively.
Orthotopic liver transplantation for HCV is performed with excellent results. There are no distinct advantages to the use of cyclosporine versus tacrolimus immunosuppression when patient and graft survival are considered. Re-OLT is an important option in the treatment of recurrent HCV and should be performed early in the course of recurrent disease. Survival after re-OLT is not distinctively affected by cyclosporine or tacrolimus primary immunotherapy. The incidence of re-OLT for recurrent HCV or chronic rejection is low after either tacrolimus or cyclosporine therapy.
确定丙型肝炎病毒(HCV)所致终末期肝病原位肝移植(OLT)的疗效。
HCV已成为导致肝硬化和肝衰竭并进而需要进行OLT的主要原因。OLT术后复发性HCV与严重并发症相关,并可能导致移植物丢失,需要再次移植(再次OLT)。作者研究了HCV移植的疗效、初次免疫治疗的效果以及再次移植的原因。
作者对其8年期间(1990 - 1997年)的经验进行了回顾性研究,在此期间374例患者接受了HCV移植(298例[79.6%]接受了一次OLT;76例[20.4%]需要再次OLT)。中位随访时间为2年(范围0至8.3年)。190例患者的免疫抑制方案基于环孢素,132例患者基于他克莫司。在第三组患者中,治疗方案从环孢素转换为他克莫司或从他克莫司转换为环孢素(环孢素/他克莫司组)。
总体而言,1年、2年和5年的精算患者生存率分别为86%、82%和76%。环孢素组2年患者生存率为81%,他克莫司组为85%,环孢素/他克莫司组为82%。接受一次OLT的患者中,总体1年、2年和5年患者生存率分别为85%、81%和75%。环孢素组2年患者生存率为79%,他克莫司组为84%,环孢素/他克莫司组为80%。总体移植物生存率在1年、2年和5年分别为70%、65%和60%。在环孢素(68.5%)、他克莫司(64%)或环孢素/他克莫司(60%)治疗下,2年移植物生存率相似。42例(11.2%)患者在OLT术后最初30天因移植物功能障碍需要再次OLT。再次OLT的其他原因包括肝动脉血栓形成10例(2.6%)、慢性排斥反应8例(2.1%)和复发性HCV 13例(3.4%)。再次OLT后1年和2年的总体生存率分别为63%和58%。因移植物功能障碍再次OLT后1年生存率为61%,慢性排斥反应为50%,肝动脉血栓形成为60%,复发性HCV为60%。在再次OLT时,85.3%的患者病情危重(器官共享联合网络[UNOS]1级);仅14.7%的患者为UNOS 2级和3级。在因慢性排斥反应和复发性HCV进行再次OLT时,UNOS 1级患者1年生存率为38.4%,而UNOS 2级和3级患者为87.5%。在需要再次OLT的患者中,初次治疗使用环孢素(60%)、他克莫司(63%)或环孢素/他克莫司(56%)时,再次OLT后1年患者生存率无差异。使用环孢素时,3例(1.5%)患者因慢性排斥反应需要再次OLT,而使用他克莫司时为1例(0.7%)。接受他克莫司和环孢素治疗的患者中,分别有4例(3%)和7例(3.6%)因复发性HCV需要再次OLT。
HCV原位肝移植效果良好。在考虑患者和移植物生存率时,使用环孢素与他克莫司免疫抑制无明显优势。再次OLT是治疗复发性HCV的重要选择,应在复发性疾病早期进行。再次OLT后的生存率不受环孢素或他克莫司初次免疫治疗的显著影响。他克莫司或环孢素治疗后,因复发性HCV或慢性排斥反应进行再次OLT的发生率较低。