【摘要】：背景： 肝移植術(shù)后免疫抑制劑的應(yīng)用使得肝移植,特別是良性疾病肝移植存活率顯著上升。但長期使用免疫抑制劑,特別是鈣調(diào)酶抑制劑使得肝移植術(shù)后腎功能不全、新生糖尿病、新發(fā)腫瘤、病毒感染的發(fā)生率和病死率增加。目前研究提出鈣調(diào)酶抑制劑最小化方案,通過延遲使用、替換或減量、撤除等方式,降低其副作用。但對于長期存活患者,遠期免疫抑制方案缺乏研究。 方法： 本研究通過對112例良性疾病肝移植長期存活患者術(shù)后他克莫司濃度監(jiān)測以及相關(guān)指標隨訪,針對術(shù)后他克莫司濃度是否低于3ng/ml及以下分為低濃度組和普通濃度組,對于是否術(shù)后3年內(nèi)穩(wěn)定低于5ng/ml及以下分為早期組和晚期組,通過統(tǒng)計學(xué)比較,對上述分組術(shù)后排斥反應(yīng)發(fā)生率、術(shù)后遠期并發(fā)癥進行比較并對低濃度組的預(yù)測因素進行分析。 結(jié)果： 無論是他克莫司濃度穩(wěn)定低于3ng/ml及以下還是3年內(nèi)穩(wěn)定低于5ng/ml不增加排斥反應(yīng)發(fā)生率,且降低濃度后1年內(nèi)肝功能未見明顯異常(肝功能為降低濃度前基線2倍以下)。術(shù)后3年內(nèi)穩(wěn)定低于5ng/ml及以下可降低肝移植術(shù)后乙肝復(fù)發(fā)、乙肝感染、新生糖尿病發(fā)病率(P0.05)。而術(shù)后6月他克莫司濃度、術(shù)前肝功能(谷丙轉(zhuǎn)氨酶、谷草轉(zhuǎn)氨酶)為術(shù)后是否可穩(wěn)定低于3ng/ml的預(yù)測因素。 結(jié)論： 我們推薦術(shù)后他克莫司濃度盡早穩(wěn)定低于5ng/ml,且把最終濃度目標定為低于3ng/ml的良性疾病肝移植長期存活患者他克莫司低濃度方案是安全可行的,且會降低患者遠期并發(fā)癥發(fā)生率,提高患者長期生存質(zhì)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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R657.3

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1 Tommaso Maria Manzia;Roberta Angelico;Paolo Ciano;Jon Mugweru;Kofi Owusu;Daniele Sforza;Luca Toti;Giuseppe Tisone;;Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients[J];World Journal of Gastroenterology;2014年34期

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