肝移植后早期使用 FK506 进行无类固醇免疫抑制治疗：前瞻性随机双盲试验的长期结果。

Early steroid-free immunosuppression with FK506 after liver transplantation: long-term results of a prospectively randomized double-blinded trial.

机构信息

Department of Transplantation and Hepatobiliarypancreatic Surgery, Hospital of Johannes Gutenberg University Mainz, Mainz, Germany.

出版信息

Transplantation. 2010 Dec 27;90(12):1562-6. doi: 10.1097/TP.0b013e3181ff8794.

DOI:10.1097/TP.0b013e3181ff8794

PMID:21048536

Abstract

BACKGROUND

The aim of this prospective, randomized, double-blinded, placebo-controlled single center study was to evaluate an early steroid-free immunosuppression in liver transplant patients.

METHODS

From March 2000 to October 2004, 110 patients were included. All patients received tacrolimus and steroids during the first 2 weeks after orthotopic liver transplantation (OLT). Thereafter, patients in the steroid group (n=54) received steroids and the remaining 56 a placebo. After 6 months, the immunosuppression for all was steroid free. Thirty patients were hepatitis C positive. Five years after inclusion, patient survival, organ survival, steroid side effects, and recirrhosis in hepatitis C virus (HCV) patients were reevaluated.

RESULTS

After 5 years, the following parameters were comparable in both groups: patient survival (P=0.236), organ survival (P=0.509), and acute rejections (P=0.409). Steroid-free immunosuppression lead to a higher rate of chronic rejections (P=0.023). Six months after OLT, there was a difference in rates of posttransplant diabetes mellitus (PTDM) (P=0.024) and hypercholesterolemia (P=0.002). However, 5 years after OLT, there was no difference in hypertension (P=0.647), PTDM (P=0.453), hypercholesterolemia (P=0.412), and osteoporosis (P=0.624). In HCV patients, we could not find any differences in patient survival (P=0.096), organ survival (P=0.424), time free from recirrhosis (P=0.647). The rate of recirrhosis was influenced by steroid bolus therapy (P=0.01) but not by avoiding continuous steroid therapy.

CONCLUSIONS

Early tapering down of steroids to a tacrolimus monotherapy is possible with comparable acute rejection rates. During steroid therapy, PTDM and hypercholesterolemia are cumulative. These side effects are reversible. The recirrhosis in HCV patients is not influenced by continuous steroid therapy but more frequent in HCV patients receiving a steroid bolus therapy.

摘要

背景

本前瞻性、随机、双盲、安慰剂对照的单中心研究旨在评估肝移植患者早期无类固醇免疫抑制的效果。

方法

2000 年 3 月至 2004 年 10 月，共纳入 110 例患者。所有患者在原位肝移植（OLT）后 2 周内接受他克莫司和类固醇治疗。此后，类固醇组（n=54）患者接受类固醇治疗，其余 56 例患者接受安慰剂。6 个月后，所有患者均停止使用类固醇。30 例患者为丙型肝炎阳性。纳入后 5 年，重新评估患者生存率、器官存活率、类固醇副作用以及丙型肝炎病毒（HCV）患者的再肝硬化情况。

结果

5 年后，两组的以下参数无显著差异：患者生存率（P=0.236）、器官存活率（P=0.509）和急性排斥反应（P=0.409）。无类固醇免疫抑制导致慢性排斥反应发生率更高（P=0.023）。OLT 后 6 个月，移植后糖尿病（PTDM）（P=0.024）和高胆固醇血症（P=0.002）的发生率存在差异。然而，OLT 后 5 年，高血压（P=0.647）、PTDM（P=0.453）、高胆固醇血症（P=0.412）和骨质疏松症（P=0.624）的发生率无差异。在 HCV 患者中，我们未发现患者生存率（P=0.096）、器官存活率（P=0.424）和无再肝硬化时间（P=0.647）存在差异。再肝硬化的发生率受类固醇冲击疗法的影响（P=0.01），但不受避免持续类固醇治疗的影响。