Mycophenolate mofetil (MMF) effect on anti-HLA donor-specific antibody (DSA) after pediatric living donor transplantation
Takehisa Ueno1, Koki Takase1, Naoko Uga1, Koichi Deguchi1, Motonari Nomura1, Miho Watanabe1, Masafumi Kamiyama1, Takeshi Kimura2, Hiroomi Okuyama1.
1Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Japan; 2Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan
Introduction: Anti-HLA donor-specific antibody (DSA) was sometimes observed in pediatric living donor liver transplantation (LDLT). The therapeutic strategies for post-transplant DSA in pediatric LDLT remain controversial. Mycophenolate mofetil (MMF), which acts to inhibit T and B cell proliferation as an antimetabolite, is mainly used as a third agent immunosuppression for renal sparing and anti-rejection in liver transplantation. This study aimed to examine the efficacy of MMF after pediatric LDLT based on the mean fluorescence intensity (MFI) of DSA.
Method: The patients under 19 years old who received LDLT in our institution were gathered. Patients who underwent DSA measurement at least twice at an interval of 1 year or more were included in the study. Our standard tacrolimus and steroid-based immunosuppression were administrated. Patients with a maximum MFI > 5000 were defined as having high DSA-MFI. MMF was added to selected children to indicate high DSA-MFI. MMF was administrated twice a day orally. First, MMF was given at a dosage of 40-50mg/kg/day. We evaluated the effects of MMF for maximum DSA-MFI in a group treated with MMF and a group not treated with MMF.
Result:Twenty-two patients were included. There were 16 girls and six boys. Original diseases were biliary atresia (n=17), Alagille syndrome (n=2), metabolic disorders (n=2) and hepatoblastoma (n=1). The median age at the time of transplantation was 2.1 years (0.6 years to 17.3 years), and the age at the time of final DSA measurement was 14.8 years(5.7 years to 30.4 years). There were three patients with preformed DSA and 19 patients with de novo DSA. The DSA at the first measurement was DR locus (n=7), DQ locus(n=15), and the initial DSA was evaluated at a median of 9.3 years (0-23.7 years) after LDLT. Maximum MFI was median 22823(6979-26758) at initial MFI measurement. The interval between the initial and latest DSA measurement was median 22 months (12-110 months). Eight patients were in the MMF administration group and 14 in the non-administration group. MFI max decreased in 6 patients (75%) in the MMF treatment group but only in 2 patients (14%) in the non-treatment group. The change in MFI max was mean -3300 for the MMF-treated group, whereas +5891 for the non-treated group, indicating a significant decrease in MFI max in the treated group (p=0.01). One patient had gastrointestinal symptoms and required a dose reduction of MMF, but no other adverse events were observed.
Conclusion: MMF was helpful for high DSA MFI after pediatric LDLT. Future studies are required to determine the effects of decreased MFI on graft function and prognosis.
[1] anti HLA antibody
[2] mean fluorescence intensity
[3] graft survival
[4] donor specific antibody
[5] living donor liver transplant