Liver Transplantation: Tacrolimus Blood Levels Variation and Survival, Rejection and Death Outcomes

Abstract

BACKGROUND: Immunosuppressive drugs have important role in transplant of solid grafts, it aim avoid episodes of acute and chronic rejection and improving graft survival and patient survival. In Brazil, in 2016, liver transplantation was the third most frequent, with 1,880 transplants performed, of which 150 in Rio Grande do Sul. Several studies evaluated the association between variability in blood levels of immunosuppressive tacrolimus and late acute cellular graft rejection. OBJECTIVE: To investigate the association of tacrolimus blood levels with clinical outcomes late acute cellular rejection, death, patient survival and graft survival in patients undergoing liver transplantation. METHODS: This is a retrospective longitudinal study including patients submitted to adult liver transplantation by the Liver Transplantation Group in the Santa Casa de Misericórdia Hospital of Porto Alegre, from January 2006 to January 2013, and who used tacrolimus as immunosuppressive therapy. RESULTS: Of the 127 patients included in the study, the majority were male (70.1%), 52-60 years old (33.9%) at the transplant. The most frequent causes of liver transplantation in this series were hepatitis C virus and hepatocellular carcinoma (24.4%) and alcohol (15.7%). Thirteen patients had late acute cellular rejection (10.2%); of these, three had two episodes. Regarding severity classification, seven patients had mild late acute cellular rejection. The mean time of rejection after liver transplantation was 14 months (ranging from 8 to 33 months). Overall survival was 8.98 years. Regarding tacrolimus blood levels, 52 patients with a variation ≥2 standard deviations were identified. Of these patients, eight had rejection; however, the association was not significant (P=0.146). A significant association was found between variation ≥2 standard deviations in tacrolimus blood levels and death (P=0.023) and survival (P=0.019). Regarding 5-year follow-up of graft survival, being two standard deviations above increases by 2.26 times the risk of transplanted graft loss, and for each unit of increase of standard deviation of tacrolimus blood levels there is a two-fold increase in the risk of graft loss in 5 years. CONCLUSION: Increased risk of graft loss associated with increased standard deviations of tacrolimus blood levels may indicate the need for more rigorous and prospective monitoring of tacrolimus blood levels.

Nível Sérico dos Imunossupressores como Marcador de Efetividade da Educação farmacêutica no Transplante de Órgãos Sólidos

“…De acordo com a literatura, percebe-se um predomínio de pacientes transplantados do sexo masculino e com idade superior a 50 anos, independentemente do tipo de órgão transplantado, fígado ou pulmão. 18,19 Nesta análise foi identificada prevalência de pacientes transplantados hepáticos acima de 51 anos, sendo a cirrose pelo vírus da Hepatite C a principal doença de base. Tal dado poderia ser justificado pela inovação no tratamento farmacológico do HCV, assim como no investimento para o acesso ao tratamento universal dos portadores, refletindo no prolongamento da qualidade de vida destes pacientes.…”

Nomograms for Predicting the Incidence of Late-Onset Acute Cellular Rejection in Patients After Pediatric Liver Transplantation

“…Studies have confirmed that LACR has a significant effect on graft degradation and subsequent graft failure in older children (9). One study showed that an increase in the standard deviation of tacrolimus blood concentration will increase the risk of LACR, indicating the need for more rigorous and prospective monitoring of tacrolimus blood concentrations (10). However, the tacrolimus concentrations predicting LACR at various stages after pLT have not been elucidated, yet it would be very useful to determine the occurrence, development, and risk factors of LACR after pLT.…”