Mycophenolate Mofetil Can Be Used as Monotherapy Late After Liver Transplantation

Abstract

We report our experience with calcineurin inhibitor (CNI) withdrawal and MMF monotherapy in 50 adult liver transplant (OLT) recipients with CNI-related toxicity. Thirty-four patients had chronic renal dysfunction (CRD) associated with arterial hypertension, 11 had only CRD and other five patients had hypertension. The mean time between OLT and introduction of MMF was 81 months. After the introduction of MMF, CNI was progressively reduced and withdrawn if possible. At the end of the follow up (mean time: 18 months) CNI was withdrawn in 39 patients (78%), and there was a significant decrease from baseline in serum creatinine (1.81-1.49 mg/dL; p < 0.0001), BUN (76.6-52.8 mg/dL; p < 0.0001) and uric acid (9-7.5 mg/dL; p < 0.0001) levels, and an increase in creatinine clearance (44.7-55.1 mL/min; p < 0.0001). Excluding patients who developed graft rejection and two patients who died, CRD improved in 32 of 40 patients (80%), and arterial hypertension improved in 22 of 29 patients (76%). Five patients (10%) developed acute rejection, and one patient (2%) chronic rejection. Twenty-six patients (52%) experienced side-effects, with asthenia, herpes virus infection, and diarrhea being the most common. Only eight patients (16%) required MMF dose reduction. In conclusion, MMF monotherapy late after OLT improves CRD and hypertension in most patients, is safe and well tolerated.

Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy

“…The incidence of acute rejection was lower in patients treated with MMF, but patient and graft survival rates were similar at 1 year. In addition to replacing azathioprine as part of a triple therapy regimen after liver transplantation, MMF may also have a role in permitting CNI dose reduction or withdrawal in recipients with renal dysfunction [80][81][82], although such a strategy is not completely without risk [81].…”

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

“…Most studies showed improvement in renal function, but recovery was more pronounced when CNI were totally withdrawn (6,7). 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.…”

Hot-topic debate on kidney function: Renal-sparing approaches are beneficial

“…25 More recent studies focusing on patients with CNI-related side effects (renal dysfunction and metabolic side effects in particular) over the long term have been more promising. [26][27][28][29] In these series, MMF monotherapy was most often considered more than 1 year after transplantation. In all cases, MMF was introduced, and in parallel, CNIs were slowly tapered for discontinuation within 4 to 6 months.…”

“…26 In these select patients, the rate of acute rejection was low (<10%). 29 Chronic rejection was a rare event, and CNIs had to be reintroduced in only a few patients. 28 However, because of the potential risk of rejection and graft loss, physicians should be very cautious with CNI withdrawal and MMF monotherapy and should closely monitor liver function tests.…”