Orlando Giuseppe, Baiocchi Leonardo, Cardillo Andrea, Iaria Giuseppe, De Liguori Carino Nicola, De Luca Linda, Ielpo Benedetto, Tariciotti Laura, Angelico Mario, Tisone Giuseppe
Transplant and General Surgery Unit, S. Eugenio Hospital, Italy.
Liver Transpl. 2007 Jan;13(1):46-54. doi: 10.1002/lt.20926.
Although mycophenolate mofetil (MMF) monotherapy has been successfully used in liver transplant recipients suffering from calcineurin-inhibitor (CNI)-related chronic toxicity, still no consensus has been reached on its safety, efficacy and tolerability. We attempted the complete weaning off CNI in 42 individuals presenting chronic renal dysfunction and/or dyslipidemia and/or arterial hypertension and simultaneously introduced 1.5 gm/day MMF. CNI could be completely withdrawn in 41 cases. A total of 32 (75%) patients are currently on <or=1.5 gm/day of MMF. Mean follow-up from the introduction of MMF is 31.5 months and mean length of follow-up from the beginning of MMF monotherapy is 27.3 months. Renal function improved in 31/36 (89%) cases. Blood levels of cholesterol and triglycerides decreased in 13 of 17 (76%) and 15 of 17 (89%) patients, respectively. Arterial hypertension improved in 4 of 5 (80%) cases. A total of 8 patients showed a single episode of fluctuation of liver function tests during tapering off CNI. This feature was interpreted as an acute rejection (AR), based on the resolution of the clinical setting after escalation of MMF daily dose to 2 gm. A further patient developed a biopsy-proven AR insensitive to MMF adjustment, requiring reinstitution of the CNI dose. No deaths or major toxicity requiring MMF discontinuation occurred. In conclusion, low dose MMF monotherapy is safe, effective, and well tolerated.
尽管霉酚酸酯(MMF)单药治疗已成功应用于患有钙调神经磷酸酶抑制剂(CNI)相关慢性毒性的肝移植受者,但在其安全性、有效性和耐受性方面仍未达成共识。我们尝试让42例出现慢性肾功能不全和/或血脂异常和/或动脉高血压的患者完全停用CNI,同时引入1.5克/天的MMF。41例患者能够完全停用CNI。目前共有32例(75%)患者服用≤1.5克/天的MMF。从引入MMF开始的平均随访时间为31.5个月,从MMF单药治疗开始的平均随访时长为27.3个月。36例中的31例(89%)肾功能得到改善。17例患者中的13例(76%)胆固醇水平以及17例中的15例(89%)甘油三酯水平下降。5例中的4例(80%)动脉高血压得到改善。共有8例患者在逐渐停用CNI期间出现单次肝功能检查波动。基于将MMF每日剂量增至2克后临床症状缓解,这一特征被解释为急性排斥反应(AR)。另有1例患者经活检证实为对MMF调整不敏感的AR,需要重新使用CNI剂量。未发生需要停用MMF的死亡或重大毒性事件。总之,低剂量MMF单药治疗安全、有效且耐受性良好。