MYCOPHENOLATE MOFETYL (MMF) THERAPY USED IN A PRIMARY IMMUNOSUPPRESSIVE REGIMEN FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION (OLT)

Abstract

A191 Aims: MMF is a new immunosuppressive (IS) drug for use following OLT which may decrease acute rejection and lead to a reduction in calcineurin inhibitors (CNI) in case of nephrotoxicity. Few studies have evaluated its early use in a primary IS regimen on a large cohort of liver transplant recipients. The aims of this study were: a) to evaluate the impact of MMF on patient survival, frequency of acute and chronic allograft rejection, rate of post-transplant infectious events; and b) to quantify CNI reduction in case of nephrotoxicity. Methods: Patients with MMF in a primary IS regimen (group A) were compared to those without initial MMF (group B). Prognostic analysis used χ2, Kruskal-Wallis, T test and log-rank tests, and the Kaplan Meier method. Results: From 1995 to 2003, 169 adult recipients (173 OLT) were followed for 34 months (109 males, 60 females; age: 48 years). An IS regimen with MMF-CNI-corticosteroids was prescribed in group A (95 consecutive patients, mean follow-up 30.5±10 months), and an azathioprine-CNI-corticosteroid regimen was used in group B (74 patients, mean follow-up 44.4±16 months). Within group B, MMF was never used in 48 patients and secondarily introduced in 26 patients in order to reduce CNI (nephrotoxicity in 20% of cases). Post-transplant survival was significantly higher in group A than in group B at 1 year (90.1±3,1% vs 78.4±4.8%, p=0.02) and 2 years (87±3.8% vs 77±4.9%, p=0..05). Acute and chronic rejection rates were significantly lower in group A than in group B (18.9% vs 43.2%, p= 0.0005 and 0% vs 3.9%, p=0.05). The retransplantation rate did not differ in the two groups (1.1% vs 4.1%). The global rate of early bacterial and CMV-induced events did not differ in the two groups (group A: 34% and 35% versus group B: 31% et 29%). In group A, a decrease in the dose of MMF dose was required in 35% of cases and total arrest in 23% of cases. Frequencies of renal dysfunction and severe renal dysfunction (clearance of creatinine <80 ml/min or <30 ml/min) did not differ in the 2 groups at one year (51.7% vs 48.3% and 0% vs 0%), 2 years (37.7% vs 62.3% and 0% vs 1.9%) or 3 years (72.7% vs 83.7%, and 9.1% vs 6.4%). In group B, secondary use of MMF (mean 36 months post-OLT) in 20 transplant recipients with renal dysfunction led to a reduction in CNI (cyclosporine 0.6 mgkg-1d-1 vs 2.6 mgkg-1d-1, p=0.002, tacrolimus 0.02 mgkg-1d-1 vs 0.08, p=0.009) and a stabilization of renal function with an increase in creatinine clearance of 8 ml/min in 1 year compared to patients from group B without MMF. Conclusions: MMF is an efficient and safe immunosuppressant following OLT which reduces rejection and improves 1- and 2-year survival without significantly increased infectious hazard. Moreover, it enables reduction of CNI and maintenance of renal function in cases of nephrotoxicity.