DiMartini Andrea, Fontes Paulo, Dew Mary Amanda, Lotrich Francis E, de Vera Michael
Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Liver Transpl. 2008 Jun;14(6):815-22. doi: 10.1002/lt.21427.
Calcineurin-inhibiting immunosuppressive medications are the mainstay of posttransplant immunosuppression. Although these highly beneficial drugs are critical for posttransplant survival, significant numbers of transplant recipients experience side effects, some requiring a switch to a different immunosuppressive regimen. Neurotoxicity is one of the most debilitating side effects because of its impact on mental status and cognition. As our center uses tacrolimus as the initial immunosuppressant for all liver transplant (LTX) recipients, we were interested in those patients who required a switch because of neurotoxic side effects. Over a 5-year period, 827 adult LTX recipients received their first graft at our center. Ninety-four patients were no longer on tacrolimus by 2 months post-LTX (86 switched because of concerns over neurotoxicity, and 8 switched because of renal function concerns). Of those experiencing neurotoxic side effects, the majority (64%) had altered mental status, and 26% had seizures (first onset post-LTX). On the basis of our prior work, we hypothesized that patients with a pre-LTX history of excessive alcohol use would be at higher risk for neurotoxic effects. We also hypothesized that the elderly and those who had more advanced illness (that is, higher Model for End-Stage Liver Disease scores) at LTX would be at risk as well. We found that patients with a pre-LTX diagnosis of alcoholic liver disease were not more likely to be switched from tacrolimus. Furthermore, we found that in addition to older age and higher Model for End-Stage Liver Disease scores, poorer hepatic functioning was significantly associated with a switch from tacrolimus. We discuss the implications of these findings and the relevance for future clinical care in these high-risk patients.
钙调神经磷酸酶抑制性免疫抑制药物是移植后免疫抑制的主要手段。尽管这些非常有益的药物对移植后的存活至关重要，但仍有相当数量的移植受者出现副作用，有些需要改用不同的免疫抑制方案。神经毒性是最使人衰弱的副作用之一，因为它会影响精神状态和认知。由于我们中心将他克莫司作为所有肝移植（LTX）受者的初始免疫抑制剂，我们对那些因神经毒性副作用而需要换药的患者很感兴趣。在5年的时间里，827名成年LTX受者在我们中心接受了首次移植。94名患者在LTX后2个月时不再使用他克莫司（86名因担心神经毒性而换药，8名因肾功能问题而换药）。在出现神经毒性副作用的患者中，大多数（64%）有精神状态改变，26%有癫痫发作（首次发作于LTX后）。根据我们之前的研究，我们假设LTX前有过量饮酒史的患者发生神经毒性作用的风险更高。我们还假设老年人以及LTX时病情更严重（即终末期肝病评分更高）的患者也有风险。我们发现，LTX前诊断为酒精性肝病的患者不太可能从他克莫司换药。此外，我们发现，除了年龄较大和终末期肝病评分较高外，肝功能较差与从他克莫司换药显著相关。我们讨论了这些发现的意义以及对这些高危患者未来临床护理的相关性。
