Background: Chronic antibody mediated rejection (CAMR) which was associated with the anti–human leukocyte antigen donor-specific alloantibodies (DSA) after living donor liver transplantation (LDLT) can influence the graft survival. The aims of this study were to reveal the risk factors of CAMR and propose the optimal treatment for CAMR in pediatric LDLT recipients.
Methods: Among 305 LDLT recipients, we conducted cross-sectional study for 44 pediatric recipients who had liver biopsy because of positive episode of DSA and were followed up for >3 years after primary LDLT. The median recipients’ age at LDLT was 9.5 months and 29 / 44 (65.9%) were indicated due to cholestatic disease. Liver biopsy was performed in the DSA positive cases with mean fluorescence intensity (MFI) >1000.
Results: The median years from LDLT to liver biposy was 6.5 years (1.7-9.3 years). From the 305 patients, 78 (25.6%) had DSA (Only Class I: 5, Only Class II: 33, Both Class I and II: 6). Liver biopsy specimens could be scored for the 44 DSA positive recipients. CAMR was detected in 13 recipients (4.3% of cohort, and 29.5% of DSA positive), Other 31 recipients were diagnosed as follow: chronic rejection 16, late TCMR 2, plasma cell-rich rejection 1, normal or mild fibrosis 12. In the multivariate analysis, high MFI and low graft-to-recipient body weight ratio (GRWR) was associated with the occurrence of CAMR (Odds ratio (95% C.I.): 34.3 (2.03-579.3) and 0.048 (0.002-0.97), respectively). Etiology, ABO incompatibility, immunosuppression, gender, recipient and donor age at operation, and post-transplant follow-up duration were not found as risk factors for CAMR. We performed 4 cases of liver biopsy to assess the therapeutic effect for CAMR one year after first biopsy. Although increasing the dosage of tacrolimus made the fibrosis improve in one case with low MFI, it was not effective in two cases with MFI>10000. Additional Mycophenolate mofetil (MMF) improved the fibrosis in one case with MFI>10000.
Conclusion: Liver biopsy should be done to diagnose CAMR especially in the case with high MFI and low GRWR. Additional immunosuppression drugs such as MMF should be used in the case with MFI>10000.