Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001, Minas Gerais, Brazil; Department of Structural Biology, Federal University of Alfenas, Alfenas, 37130-001, Minas Gerais, Brazil.
Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001, Minas Gerais, Brazil; Department of Pathology and Parasitology, Federal University of Alfenas, Alfenas, 37130-001, Minas Gerais, Brazil.
Transplant Rev (Orlando). 2018 Jul;32(3):157-167. doi: 10.1016/j.trre.2018.04.003. Epub 2018 Apr 17.
Although contraindicated for decades, heart transplantation (HT) has finally become a feasible therapeutic option for the treatment of Chagasic patients with end-stage heart failure. Part of the success in achieving acceptable survival rates after HT is due to the enhancement of the pharmacological management of allograft rejection and reactivation of Trypanosoma cruzi infection.
By using the framework of a systematic review, we investigated if Chagasic patients who have undergone a HT are treated with similar immunosuppressive and antitrypanosomal regimens in endemic and non-endemic countries and exhibits similar T. cruzi reactivation, allograft rejection and survival rates. From a structured search in PubMed/Medline, Scopus, and Web of Sciences databases, 30 clinical studies were reviewed.
Although immunosuppressive regimens are variable in endemic and non-endemic countries, the current evidence supports the administration of lower doses of corticosteroids, adjusted cyclosporine levels (100-150 ng/mL) 3 months after HT, and azathioprine rather than mycophenolate mofetil to reduce the risk of T. cruzi reactivation and rejection episodes. Antitrypanosomal therapy exclusively based on benznidazole, nifurtimox, and allopurinol was consistent in endemic and non-endemic countries, achieving effective results in the control of infection reactivation. The evidence that supports prophylactic antitrypanosomal therapy or administration of allopurinol alone is limited. By highlighting the main sources of research bias, we hope that our critical analysis can help to expedite clinical research and to reduce methodological bias, thereby improving the quality of evidence in new research initiatives.
尽管几十年来一直被禁忌，但心脏移植（HT）最终已成为治疗晚期心力衰竭的恰加斯病患者的可行治疗选择。HT 后实现可接受的存活率部分原因是增强了同种异体移植物排斥反应和克氏锥虫感染再激活的药物治疗管理。
通过使用系统评价框架，我们调查了在流行地区和非流行地区进行 HT 的恰加斯病患者是否接受了类似的免疫抑制和抗锥虫治疗方案，以及是否表现出相似的克氏锥虫再激活、同种异体移植物排斥反应和存活率。通过对 PubMed/Medline、Scopus 和 Web of Sciences 数据库进行结构化搜索，共回顾了 30 项临床研究。
尽管免疫抑制方案在流行地区和非流行地区有所不同，但目前的证据支持使用较低剂量的皮质类固醇、调整环孢素水平（HT 后 3 个月为 100-150ng/mL）以及使用硫唑嘌呤而不是霉酚酸酯来降低克氏锥虫再激活和排斥反应的风险。抗锥虫治疗完全基于苯并咪唑、硝呋替莫和别嘌呤醇，在流行地区和非流行地区均取得了有效的结果，可有效控制感染再激活。支持预防性抗锥虫治疗或单独使用别嘌呤醇的证据有限。通过突出研究偏倚的主要来源，我们希望我们的批判性分析能够有助于加快临床研究并减少方法学偏倚，从而提高新研究计划中的证据质量。
