Mycophenolate Mofetil Effect and Trough Level Under 2-Year Old in Pediatric Living Donor Liver Transplantation

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Abstract

Introduction

Mycophenolate mofetil (MMF) is prodrug of mycophenolic acid to improve oral bioavailability. MMF are mainly used as third agent immunosuppression for renal sparing and anti-rejection in liver transplantation. However there have been only few reports of MMF use for very young children after living donor liver transplantation (LDLT). The purpose of this study was to examine the safety and efficacy based on mycophenolic acid (MA) trough level in the under 2 –year old patients.

Methods

The patients under 2-year old who received LDLT between Nov. 2015 and October 2017 were enrolled. Our standard tacrolimus and steroid based immunosuppression were administrated. MMF was added to selected children for the indications including renal sparing, refractory acute cellular rejection (ACR), fulminant hepatitis and preexisting antibody. MMF was administrated twice a day orally. First MMF was given at dosage of 40-50mg/kg/day. Dose was increased to target MA trough level 3 ng/ml. Body weight, height, MMF dosage, MA trough level, ACR episode, serum cystatin C and adverse effects were analyzed.

Results

Seven patients received MMF for renal sparing (n=2), refractory ACR (n=2), fulminant hepatitis (n=2) and preexisting antibody (n=1). Original diseases were biliary atresia (n=5) and fulminant hepatitis (n=2). Median age at transplant was 7 months (ranged 6month to 12month). Median first administration of MMF were post-operative day (POD) 18 (ranged POD 1 to POD 39). Observation period ranged 51 to 730 days. Last available median trough level was 2ng/ml (ranged1.4 to 3.3 ng/ml). Median dose were 84mg/kg and 2012 mg/m2 at last available median trough level. Regression line between MMF dose and MA trough level was Y=1.1*10^3X-0.54. Correlation coefficient was 0.81. There was no ACR episode after MMF was administrated. Average cystatin C serum level was decreased from 1.69 mg/L to 1.08mg/L in renal sparing patients (n=2). One patient whose indication was refractory ACR discontinued MMF due to infection. Other patients were tolerable to MMF without adverse effect.

Discussion

MMF is now commonly used in pediatric liver transplant recipients, but no clear recommendations about the dosing regimen have been made for very young child. Recommend pediatric dose is 300-600mg/m2/day, however young child require more MMF dose to maintain MA trough level in our study. Even if most patients received higher dose that previously documented for pediatric dose, they did not show adverse effect. The patient developed infection might be over immunosuppression because of treating ACR. MMF showed good anti ACR effect at higher dose.

Conclusion

MMF use for the patients under 2-year old after LDLT were tolerable. However they required more dose than that of older patients.

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