肝细胞癌肝移植术后基于西罗莫司的从头免疫抑制：长期疗效和副作用

De novo sirolimus-based immunosuppression after liver transplantation for hepatocellular carcinoma: long-term outcomes and side effects.

作者信息

Toso Christian, Meeberg Glenda A, Bigam David L, Oberholzer Jose, Shapiro A M James, Gutfreund Klaus, Ma Mang M, Mason Andrew L, Wong Winnie W S, Bain Vincent G, Kneteman Norman M

机构信息

Department of Surgery, Section of Hepatobiliary, Pancreatic and Transplant Surgery, University of Alberta, Edmonton, Canada.

出版信息

Transplantation. 2007 May 15;83(9):1162-8. doi: 10.1097/01.tp.0000262607.95372.e0.

DOI:10.1097/01.tp.0000262607.95372.e0

PMID:17496530

Abstract

BACKGROUND

We report long-term outcomes and side effects after transplantation for hepatocellular carcinoma (HCC) using de novo, sirolimus-based immunosuppression (IS).

METHODS

A total of 70 patients with HCC (mean age: 54.4+/-7 years, female/male: 12/58) were transplanted and included in the study. Immunosuppression included de novo sirolimus, low-dose calcineurin inhibitor for 6 to 12 months, with short-course (3 months) or no steroids.

RESULTS

After 49 months-median follow-up, eight patients have experienced an HCC recurrence, 2 of 34 when Milan criteria were respected (6%) and 6 of 36 when beyond Milan criteria (17%). One- and 4-year tumor-free survivals were 85 and 73%, when Milan criteria were respected and 82% and 75% when they were not, respectively. (P=0.9). After recurrence, mean survival was 23+/-28 months. Half (35 of 70) of the patients experienced a rejection. Incisional hernia (24 of 70, 34%), wound infection (12 of 70, 17%), anemia (39 of 70, 56%), leucopenia (39 of 70, 56%), high triglyceride (43 of 70, 61%), and cholesterol (28 of 70, 40%) levels and mouth ulcers (20 of 70, 29%) were among the most frequent complications. No hepatic artery thrombosis was observed.

CONCLUSIONS

These data suggest that de novo sirolimus-based immunosuppression is associated with satisfactory outcomes after transplantation, even in selected patients beyond Milan criteria. The protocol has proven safe, with an acceptable side-effect profile. This study supports the conduct of larger randomized trials investigating sirolimus after transplantation for HCC.

摘要

背景

我们报告了使用基于西罗莫司的初始免疫抑制（IS）方案进行肝细胞癌（HCC）移植后的长期疗效和副作用。

方法

共有70例HCC患者（平均年龄：54.4±7岁，女性/男性：12/58）接受移植并纳入本研究。免疫抑制方案包括初始使用西罗莫司、低剂量钙调神经磷酸酶抑制剂使用6至12个月，联合短疗程（3个月）或不使用类固醇。

结果

经过49个月的中位随访，8例患者出现HCC复发，符合米兰标准的34例患者中有2例（6%）复发，超出米兰标准的36例患者中有6例（17%）复发。符合米兰标准时，1年和4年无瘤生存率分别为85%和73%，不符合米兰标准时分别为82%和75%。（P = 0.9）。复发后，平均生存时间为23±28个月。一半（70例中的35例）患者发生了排斥反应。最常见的并发症包括切口疝（70例中的24例，34%）、伤口感染（70例中的12例，17%）、贫血（70例中的39例，56%）、白细胞减少（70例中的39例，56%）、高甘油三酯血症（70例中的43例，61%）、高胆固醇血症（70例中的28例，40%）以及口腔溃疡（70例中的20例，29%）。未观察到肝动脉血栓形成。