良性疾病肝移植长期存活患者他克莫司低浓度方案研究

发布时间：2019-02-20 19:30

【摘要】：背景：肝移植术后免疫抑制剂的应用使得肝移植,特别是良性疾病肝移植存活率显著上升。但长期使用免疫抑制剂,特别是钙调酶抑制剂使得肝移植术后肾功能不全、新生糖尿病、新发肿瘤、病毒感染的发生率和病死率增加。目前研究提出钙调酶抑制剂最小化方案,通过延迟使用、替换或减量、撤除等方式,降低其副作用。但对于长期存活患者,远期免疫抑制方案缺乏研究。方法：本研究通过对112例良性疾病肝移植长期存活患者术后他克莫司浓度监测以及相关指标随访,针对术后他克莫司浓度是否低于3ng/ml及以下分为低浓度组和普通浓度组,对于是否术后3年内稳定低于5ng/ml及以下分为早期组和晚期组,通过统计学比较,对上述分组术后排斥反应发生率、术后远期并发症进行比较并对低浓度组的预测因素进行分析。结果：无论是他克莫司浓度稳定低于3ng/ml及以下还是3年内稳定低于5ng/ml不增加排斥反应发生率,且降低浓度后1年内肝功能未见明显异常(肝功能为降低浓度前基线2倍以下)。术后3年内稳定低于5ng/ml及以下可降低肝移植术后乙肝复发、乙肝感染、新生糖尿病发病率(P0.05)。而术后6月他克莫司浓度、术前肝功能(谷丙转氨酶、谷草转氨酶)为术后是否可稳定低于3ng/ml的预测因素。结论：我们推荐术后他克莫司浓度尽早稳定低于5ng/ml,且把最终浓度目标定为低于3ng/ml的良性疾病肝移植长期存活患者他克莫司低浓度方案是安全可行的,且会降低患者远期并发症发生率,提高患者长期生存质量。
[Abstract]:Background: immunosuppressive agents after liver transplantation significantly increase the survival rate of liver transplantation, especially in benign diseases. But long-term use of immunosuppressive agents, especially calmodulase inhibitors, has increased the incidence and mortality of renal dysfunction, neonatal diabetes, new tumors, and viral infections after liver transplantation. At present, a scheme to minimize calmodulin inhibitors is proposed to reduce the side effects of calmodulin inhibitors by delaying their use, replacing or reducing them, and removing them. However, for long-term survival patients, long-term immunosuppressive protocols are not studied. Methods: the concentration of tacrolimus was monitored in 112 patients with long-term survival after liver transplantation for benign diseases and the related indexes were followed up. Whether the concentration of tacrolimus was lower than that of 3ng/ml or not was divided into two groups: low concentration group and normal concentration group, and whether the concentration of tacrolimus was lower than that of 5ng/ml within 3 years after operation and was divided into early group and late group by statistical comparison. The incidence of postoperative rejection and long-term complications were compared and the predictive factors of low concentration group were analyzed. Results: whether tacrolimus concentration was lower than 3ng/ml or lower than 5ng/ml for 3 years did not increase the incidence of rejection. There was no significant abnormality of liver function within 1 year after the decrease (liver function was less than 2 times the baseline before the reduction of the concentration). Stable lower than 5ng/ml and below 3 years after liver transplantation can reduce the recurrence of hepatitis B, hepatitis B infection, the incidence of new-born diabetes (P0.05). Six months after operation, tacrolimus concentration and preoperative liver function (alanine aminotransferase, alanine aminotransferase) were the predictors of postoperative stability compared with 3ng/ml. Conclusion: it is recommended that tacrolimus should be stable below 5 ng / ml as soon as possible after operation, and the final concentration target is lower than 3ng/ml in patients with long term survival of liver transplantation for benign diseases. It is safe and feasible to use tacrolimus low concentration regimen. And will reduce the incidence of long-term complications and improve the long-term quality of life of patients.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R657.3

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