Rescue therapy with sirolimus in a renal transplant recipient with tacrolimus-induced hepatotoxicity

Abstract

Calcineurin inhibitors at elevated serum concentrations frequently cause mild elevation of the liver chemistries. Although rare, severe hepatotoxicity is their serious complication. A 54-year-old man with end-stage renal disease due to chronic glomerulonephritis without biopsy received a renal allograft from the deceased donor. Eleven days after transplantation severe liver injury (AST up to 421 IU/L, ALT 1242 IU/L, and GGT 212 IU/L) with the serum bilirubin within the normal range was recorded. Tacrolimus trough level was 5.5 ng/mL. Liver ultrasound and color-Doppler of the portal system were normal. Liver failure completely resolved after withdrawal of the calcineurin inhibitor and switch to sirolimus. After 9 months of follow-up our patient has excellent graft and liver function. Awareness of the possible association of tacrolimus use with hepatotoxicity is important to timely discontinuation of the causative agent, and to introduce sirolimus as the rescue therapy.

Incidence, clinical features and risk factors of tacrolimus induced idiosyncratic liver injury in renal transplant recipients: A nested case-control study

“…For example, one study reported that tacrolimus eventually resulted in cholestatic jaundice 60 days post-liver transplantation with increases in both alkaline phosphatase (ALP) and total bilirubin (TBIL) levels ( Taniai et al, 2008 ). Another study showed that liver enzyme levels increased significantly 12 days post-renal transplantation, with aspartate aminotransferase (AST) elevated to 421 U/L, alanine aminotransferase (ALT) at 1242 U/L, and serum TBIL levels within the normal range ( Mesar et al, 2013 ). Today, increasing accessibility to digital health data owing to the transition to electronic health records, together with the rising costs and known limitations of traditional clinical trials, real-world data offer enhanced research efficacy, which bridges the evidentiary gap between clinical research and practice ( Corrigan-Curay et al, 2018 ).…”

Analysis of liver function test abnormalities in kidney transplant recipients: 7 year experience

“…Franco-Esteve et al reported only a single incidence of hepatotoxicity among 47 patients treated with mTOR inhibitor monotherapy and Jacques et al reported severe sirolimus-inducedacutehepatitis 19,20. Interestingly sirolimus was a rescue therapy in one KTR who experienced tacrolimus-related hepatotoxicity 15. We found only one case of sirolimus related hepatotoxicity.…”

“…Taniai et al presented a case in which hepatotoxicity was induced by both tacrolimus and cyclosporine after living donor liver transplantation 14. A case presented by Mesar et al reported complete resolution of LFTA after withdrawal of calcineurin inhibitor (tacrolimus) and replacement with sirolimus 15. It is important to be aware of the possible association of tacrolimus with hepatotoxicity in order to discontinue therapy and replace with sirolimus in cases of hepatotoxicity.…”

Retrospective Analysis of Pre-and Post-Operative Laboratory Findings of Patients Undergoing Kidney Transplantation

“…An early increase in liver enzyme levels in kidney transplant patients may be a clinical manifestation of cytomegalovirus cytomegalovirus (CMV) infection, as well as the effect of one or more immunosuppressive therapy or the presence of a primary hepatocellular abnormality involving the bile duct. 20 In the patient group of this study, an increase was observed in AST and ALT values in the first week after transplantation. Transient elevated liver enzyme levels are a common finding in kidney transplant recipients, usually within a month of transplant.…”