RESUMO
Introducción. El tacrolimus es un medicamento inmunosupresor ampliamente usado en trasplante hepático, que presenta una gran variabilidad interindividual la cual se considera asociada a la frecuencia de polimorfismos de CYP3A5 y MDR-1. El objetivo de este estudio fue evaluar la frecuencia de los polimorfismos rs776746, rs2032582 y rs1045642 y su asociación con rechazo clínico y toxicidad farmacológica. Métodos. Se incluyeron pacientes inmunosuprimidos con tacrolimus a quienes se les realizó trasplante hepático en el Hospital San Vicente Fundación Rionegro entre 2020 y 2022, con supervivencia mayor a un mes. Se evaluaron las variables clínicas, rechazo agudo y toxicidad farmacológica. Se secuenciaron los genes de estudio mediante PCR, comparando la expresión o no en cada uno de los pacientes. Resultados. Se identificaron 17 pacientes. El 43 % de los pacientes se clasificaron como CYP3A5*1/*1 y CYP3A5*1/*3, entre los cuales se encontró asociación con aumento en la tasa de rechazo agudo clínico, al comparar con los pacientes no expresivos (100 % vs. 44 %, p=0,05); no hubo diferencias en cuanto a la toxicidad farmacológica u otros desenlaces. Se encontró el polimorfismo rs2032582 en un 50 % y el rs1045642 en un 23,5 % de los pacientes, sin embargo, no se identificó asociación con rechazo u otros eventos clínicos. Conclusiones. Se encontró una asociación entre el genotipo CYP3A5*1/*1 y CYP3A5*1/*3 y la tasa de rechazo clínico. Sin embargo, se requiere una muestra más amplia para validar estos datos y plantear modelos de medicina personalizada.
Introduction. Tacrolimus is an immunosuppressive drug widely used in liver transplantation, which presents great interindividual variability which is considered associated with the frequency of CYP3A5 and MDR-1 polymorphisms. The objective of this study was to evaluate the frequency of the rs776746, rs2032582 and rs1045642 polymorphisms and their association with clinical rejection and drug toxicity. Methods. Immunosuppressed patients with tacrolimus who underwent a liver transplant at the Hospital San Vicente Fundación Rionegro between 2020 and 2022 were included, with survival of more than one month. Clinical variables, acute rejection and pharmacological toxicity were evaluated. The study genes were sequenced by PCR, comparing their expression or not in each of the patients. Results. Seventeen patients were identified. 43% of the patients were classified as CYP3A5*1/*1 and CYP3A5*1/*3, among which an association was found with increased rates of clinical acute rejection when compared with non-expressive patients (100% vs. 44%, p=0.05). There were no differences in drug toxicity or other outcomes. The rs2032582 polymorphism was found in 50% and rs1045642 in 23.5% of patients; however, no association with rejection or other clinical events was identified. Conclusions. An association was found between the CYP3A5*1/*1 and CYP3A5*1/*3 genotype and the clinical rejection rate. However, a larger sample is required to validate these data and propose models of personalized medicine.
Assuntos
Humanos , Farmacogenética , Transplante de Fígado , Polimorfismo de Nucleotídeo Único , Transplante de Órgãos , Tacrolimo , Rejeição de EnxertoRESUMO
Portal vein thrombosis was considered a contraindication for liver transplantation. This study analyzes the perioperative complications and survival of liver transplant patients with portal vein thrombosis (PVT). A retrospective observational cohort study of liver transplant patients was conducted. The outcomes were early mortality (30 days) and patient survival. A total of 201 liver transplant patients were identified and 34 (17%) patients with PVT were found. The most frequent extension of thrombosis was Yerdel 1 (58.8%), and a portosystemic shunt was identified in 23 (68%) patients. Eleven patients (33%) presented any early vascular complication, PVT being the most frequent (12%). The multivariate regression analysis showed a statistically significant association between PVT and early complications (OR = 3.3, 95% confidence interval 1.4-7.7; p = 0.006). Moreover, early mortality was observed in eight patients (24%), of which two (5.9%) presented Yerdel 2. For Yerdel 1, patient survival according to the extent of thrombosis was 75% at 1 year and 3 years, while for Yerdel 2, it was 65% at 1 year, and 50% at 3 years (p = 0.04). Portal vein thrombosis significantly influenced early vascular complications. Furthermore, portal vein thrombosis Yerdel 2 or higher impacts the survival of liver grafts in the short and long term.
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Background: Simultaneous pancreas-kidney transplantation (SPKT) is a complex and demanding procedure with a considerable risk of morbidity and mortality. Advances in surgical techniques and organ preservation have introduced changes in care protocols. Two cohorts of patients receiving SPKT with two different protocols were compared to determine overall survival and pancreatic and renal graft failure-free survival. Methods: This retrospective observational study was conducted in two cohorts of SPKT recipient patients that underwent surgery between 2001 and 2021. Outcomes were compared in transplant patients between 2001 and 2011 (cohort 1; initial protocol) and 2012-2021 (cohort 2; improved protocol). In addition to the temporality, the cohorts were defined by a protocolization of technical aspects and medical management in cohort 2 (improved protocol), compared to a wide variability in the procedures carried out in cohort 1 (initial protocol). Overall survival and pancreatic and renal graft failure-free survival were the primary outcomes. These outcomes were determined using Kaplan-Meier survival analysis and the log-rank test. Results: Fifty-five SPKT were performed during the study period: 32 in cohort 1 and 23 in cohort 2. In the survival analysis, an average of 2546 days (95% CI: 1902-3190) was found in cohort 1, while in cohort 2, it was 2540 days (95% CI: 2100-3204) (p > 0.05). Pancreatic graft failure-free survival had an average of 1705 days (95% CI: 1037-2373) in cohort 1, lower than the average in cohort 2 (2337 days; 95% CI: 1887-2788) (p = 0.016). Similarly, renal graft failure-free survival had an average of 2167 days (95% CI: 1485-2849) in cohort 1, lower than the average in cohort 2 (2583 days; 95% CI: 2159-3006) (p = 0.017). Conclusions: This analysis indicates that pancreatic and renal graft failure-free survival associated with SPKT decreased significantly in cohort 2, with results related to improvements in the treatment protocol implemented in that cohort.
