Uncommon side effect of MMF in renal transplant recipients

Mycophenolate mofetil (MMF) is a potent immunosuppressive agent used in renal transplantation. Gastrointestinal and hematological side effects are commonly observed, but hepatotoxicity has not been reported. In this study, we assessed MMF-related hepatotoxicity in renal transplant recipients. A total of 124 renal transplantation recipients (RTRs) were evaluated for elevated liver enzymes associated with MMF, and 79 patients were enrolled to the study. Patients used MMF 2 g/day. The patients who had progressive increase in liver enzymes after renal transplantation and their AST, ALT, GGT, ALP, bilirubin levels, hepatitis, cytomegalovirus (CMV), abdominal ultrasonography, duration of hepatotoxicity, and decreased dosage or withdrawal of MMF were recorded. Also, we evaluated their liver enzymes while the patients were on the waiting list. Of the 79 patients, 11 patients (13.9%) had a progressive increase in liver enzymes. The median (min-max) age of the patients with MMF-hepatotoxicity was 29 (19-54) and 72.7% of them were male. None of the patients had hepatitis B or C, CMV infection, or other possible causes for elevated liver enzymes and their abdominal ultrasonography were normal. High liver enzyme levels regressed after the withdrawal (n=6) or reduce dosage (n=5) of MMF. The median time of the increase in liver enzymes was 28 (4-70) days and after 50% reduction or withdrawal of MMF, returned to normal values in 16 (4-210) days. The median levels of ALT in waiting list (I), before (II), and after (III) reduction dosage or withdrawal of MMF were 22.0 (3-22), 222.0 (51-508), and 33.0 (21-64) U/L, respectively (p I-II=0.004,p I-II=0.013, andp II-III=0.005). There were no differences for ALP, GGT, total bilirubin, and direct bilirubin levels. Also, the correlation between recovery time of ALT and persistence time of ALT elevation before adjustment of MMF was significant (r=0.739, p=0.009). Consequently, after renal transplantation, hepatotoxicity can occur due to a lot of reason including MMF usage. If hepatotoxicity related to MMF is not considered, especially in the early period of renal transplantation, resolution of hepatotoxicity can be required long term.