Mycophenolate mofetil monotherapy in liver transplant recipients: A single center experience

Abstract

The long-term use of calcineurin inhibitors (CIs) is associated with significant morbidity in liver transplant recipients. Although mycophenolate mofetil (MMF) is well tolerated, two small studies reported an unacceptable rate of acute allograft rejection in liver transplant recipients receiving MMF monotherapy. In this study, we retrospectively investigated the safety and efficacy of MMF monotherapy in liver transplant recipients. We reviewed the medical records of all patients who underwent liver transplant at our institution. Sixteen patients were identified who received MMF either as monotherapy (n ‫؍‬ 13) or with corticosteroids (n ‫؍‬ 3; 2 of them for other comorbid conditions), and these patients were studied to determine the efficacy and complications. Fifteen (15/16) patients were converted from a CI to MMF because of renal insufficiency. Patients were converted to MMF monotherapy after a median of 2,056 days (range, 606-5,893) after liver transplantation. The median postconversion follow-up was 668 days (range, 60-1,509). Four patients required dialysis despite conversion; of those patients not requiring dialysis, serum creatinine stabilized and showed a trend toward improvement (2.51 ؎ 1.12 mg/dL to 1.85 ؎ .58 mg/dL, P ‫؍‬ .1). However, there were 3 episodes (47, 107, and 1,203 days after conversion) of severe, irreversible allograft rejection after conversion resulting in death in 2 patients and necessitating retransplantation in 1 patient. There were no patient characteristics, except perhaps African-American race, that predicted the development of rejection. In conclusion, MMF monotherapy was associated with a significant risk (19%) of unpredictable, severe, and irreversible allograft rejection even among long-term transplant survivors. Caution should be exercised before converting patients to MMF monotherapy. (Liver

Sustained Renal Response to Mycophenolate Mofetil and CNI Taper Promotes Survival in Liver Transplant Patients with CNI-Related Renal Dysfunction

“…Apart from that, pretransplant hematuria and proteinuria were excluded in all patients, as these parameters may indicate pre-existing causes of RDF other than CNI use, such as diabetes, hypertension, or drug abuse [1]. Thus, we have decided from a risk/benefit point of view not to perform renal biopsy in our trial [20][21][22][23][24][25][26].…”

“…Previously, it has been supposed that renal improvement was induced by CNI tapering, while MMF has been added only for safety reasons [19,20,25]. However, there is increasing evidence that MMF is able to reverse structural kidney damage [34][35][36][37].…”

“…Complete replacement of the CNI by MMF monotherapy is associated with an unacceptable risk of allograft rejection [18][19][20]. The introduction of MMF followed by a significant CNI dose reduction may, however, result in early renal function improvement without increasing the immunological risk for the patient [21][22][23][24][25][26][27].…”

Mycophenolate Mofetil Monotherapy for Severe Side Effects of Calcineurin Inhibitors Following Liver Transplantation

“…To improve management of patients with CNI-induced severe side effects, complete CNI withdrawal which was then followed by MMF monotherapy had been previously evaluated in small-cohort-size studies, which reported an average 15% risk of acute rejection (6,(8)(9)(10)(11)(12)(13)(14)(15). Therefore, complete replacement of CNI followed by MMF monotherapy remains highly controversial (9,15 Figure 1. …”

Immunosuppression based on mycophenolate mofetil in stable liver transplanted patients

“…A randomized study of conversion to MMF in monotherapy, carried out by Steward SF [15], showed that 3 of their 5 patients had a graft loss, which led to study termination. According to Fairbanks KD [16] experience, 3 out of sixteen patients converted, had severe irreversible acute rejection, resulting in death in two patients and necessitating retransplantation in 1 patient. The delayed occurrence of many of these rejections (after the 3rd month) might be due to the disappearance of body storages of CNI, which in stable transplanted patients, even at very low doses, allow the maintenance of the pharmacological homeostasis necessary for immunosuppression.…”