Sixteen-Year Cohort of Liver Transplantation in the National Health System in Brazil: Analysis of Immunosuppression Maintenance Therapies.

Guilherme Fagundes Nascimento,Juliana Alvares-Teodoro,Francisco Assis Acurcio,Rosângela Maria Gomes,Ludmila Peres Gargano,Nélio Gomes Ribeiro,Tulio Tadeu Rocha Sarmento,Augusto Afonso Guerra,Mariângela Leal Cherchiglia,Charles Simão-Filho

doi:10.3389/fphar.2020.572043

Guilherme Fagundes Nascimento, Juliana Alvares-Teodoro + Show 8 more

Open Access

https://doi.org/10.3389/fphar.2020.572043

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Abstract

ObjectiveTo evaluate factors related to liver graft survival with a focus on immunosuppressive schemes based on calcineurin inhibitors (tacrolimus or cyclosporine).MethodologyThis study was carried out through an open cohort constructed by deterministic and probabilistic matching through three databases of the SUS with assessment of liver graft survival from 2000 to 2015 in Brazil. From this first cohort, a second cohort was constructed by pairing 1: 1 to more precisely assess the effect of the immunosuppressive scheme on graft survival. The Kaplan-Meier method and was used to estimate the probability of survival. Cox’s model of proportional risks was used to assess factors related to graft loss.ResultWe found 12,687 patients in the Full cohort and 470 patients in the Matched cohort. The overall graft survival rates at 1, 5, 10, and 16 years were 72.6, 63.3, 52.8, and 45.3%, respectively. Patients younger had a longer graft survival than older ones. In the Full cohort, male patients had a higher survival rate than female ones. Therapeutic schemes based on tacrolimus were more prevalent and had a better survival rate when compared to schemes that used cyclosporine. Tacrolimus without association with antiproliferative agents or rapamycin inhibitors was the therapeutic scheme associated with greater survival rate in both cohorts (HR = 0.81, 95% CI = 0.72–0.91), (HR = 0.50, 95% CI = 0.30–0.85). In addition, white-skinned patients had longer survival rate in both cohorts (HR = 0.55, 95% CI = 0.50–0.61 and HR = 0.50, 95% CI = 0.34–0.75). On the other hand, patients who a greater time ratio without using an immunosuppressant had lower graft survival rate (HR = 6.46, 95% CI = 5.05–8.27 and HR = 6.57, 95% CI = 2.66–16.22).ConclusionThis 16-year cohort showed that the older age and the greater time ratio without using an immunosuppressant are risk factors for liver graft loss. White-skinned patients and tacrolimus-based regimens, especially tacrolimus without other immunosuppressants, are factors of better prognosis to the graft.

Highlights

Liver transplantation (LT) is well established in Brazil and worldwide
Cyclosporine was introduced as an immunosuppressive and there was a large increase in liver transplantation (LT) survival rates
We identified 12,687 patients submitted to LT in the Full cohort and 470 patients in the Matched cohort, with an average followup of 34.5 and 61.1 months, respectively

Summary

Introduction

Since the first LT in 1963 in the United States, as well as the first operation in 1968 in Brazil, patients’ survival rate has progressively improved. This was possible due to advances in surgical methods, preservation solutions, early diagnosis, peritransplant intensive care, and immunosuppressive regimens (Starzl et al, 1968; Song et al, 2014; Burra et al, 2016). After the 1980s, calcineurin inhibitors (CIs) became the standard for immunosuppressives in LT. During this decade, cyclosporine was introduced as an immunosuppressive and there was a large increase in LT survival rates. Tacrolimus became the standard drug for immunosuppression in LT (Korayem et al, 2017)

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