肝移植治疗肝脏恶性肿瘤的长期疗效及预后危险因素

Long-term survival and risk factors of prognosis after liver transplantation for malignant liver tumors

目的总结肝移植治疗肝脏恶性肿瘤的长期疗效，筛选影响移植后肿瘤复发的危险因素。方法对单中心189例肝脏恶性肿瘤患者行肝移植的临床资料进行回顾性分析。根据肿瘤临床病理类型分别计算受者累积存活率，分析肿瘤临床病理类型与肝移植术后肿瘤复发间的关系，筛选影响肿瘤复发的相关危险因素。结果189例中围手术期死亡19例，170例进入随访期，随访率为98．8％。其中166例的原发疾病为原发性肝癌，3例为肝门部胆管癌，1例肝转移癌。166例原发性肝癌肝移植者术后1、3、5和10年的总体存活率分别为52％、38％、36％和36％，其中符合米兰标准者（49例）的存活率分别为96％、87％、87％和87％，超出米兰标准者（136例）的存活率分别为42％、26％、24％和24％（P〈0．05）。肿瘤复发是造成肝癌肝移植受者随访期死亡的最主要原因（92．5％）。3例肝门部胆管癌和1例肝转移癌肝移植受者均于术后2年内肿瘤复发。符合米兰标准的肝癌肝移植受者术后肿瘤复发率（10．2％）显著低于超出米兰标准者（68．4％，P〈0．05）。而在超出米兰标准者中，无大血管侵犯者移植后肿瘤复发率（95．3％）显著低于肿瘤侵犯大血管者（55．9％，P＜0．05）。以他克莫司为主要免疫抑制剂的受者的肿瘤复发率（46．2％）低于应用环孢素A者（68．3％，P＜0．05）。移植术前肝肿瘤经皮穿刺射频消融（RF）治疗可降低受者术后肿瘤复发风险（P：0．039，OR=0．293），而术前外周血乙型肝炎病毒（HBV）DNA〉10＾4拷贝／L是移植术后肿瘤复发的高危因素（P=0．016，OR=2．294）。结论对于符合米兰标准的肝癌患者而言，肝移植的远期疗效较好；而合并大血管侵犯者肝移植的预后不佳。移植前RF治疗有助于降低术后肿瘤复发风险，移植等待期应高度重视抗HBV治疗。

Objective To investigate the long-term survival of the recipients with liver malignant tumors receiving liver transplantation and determine the risk factors of tumor recurrence after liver transplantation. Methods The follow-up data of the orthotopic liver transplantation for liver malignant tumors during 1999-2010 were retrospectively analyzed. The survival rate of different pathological tumor types was analyzed respectively. The tumor recurrence rate, mortality and morbidity, and the risk factors of the tumor recurrence were also analyzed. Results 170 recipients were followed up. The follow-up duration ranged from 8-132 months. The general 1 , 3-, 5-,10-year survival rate was 52%, 38%, 36%, and 36%respectively. The 1 , 3 , 5-, 10-year survival rate of HCC matching Millan Criteria was 96 %, 87%, 87%, 87%, while that of HCC exceeding Millan Criteria was 42%, 26%, 24%, 24%respectively （P〈0. 05）. Tumor recurrence was the main course of the death during follow-up period （92. 5% ）. The recurrence rate of HCC matching and exceeding Millan Criteria was 10. 2%, and 68. 4% respectively （P〈0. 05）. Among the recipients exceeding Millan Criteria, the recurrence rate of HCC with and without blood vessel invasion was 95. 3%, 55. 9% respectively （P〈0. 05）. Radiofrequency ablation before transplantation could decrease the risk of tumor recurrence post-transplantation （P = 0. 039, OR = 0. 293）, while the highHBV-DNA load （〉10^4 copy/L） was the risk factor of tumor recurrence. Conclusion Orthotopic liver transplantation is an effective and safe treatment for hepatocellular carcinoma matching Millan criteria. Blood vessel invasion is regarded as the contraindication of the liver transplantation of HCC. RF is an effective bridging therapy for the HCC patients, and anti-virus therapy is important during transplant waiting period.