Assessment of Donor‐Specific Human Leukocyte Antigen Antibodies Following Pediatric Liver Transplantation: Predictors, Protectors, and Clinical Relevance

Background Following pediatric liver transplantation (pLT), the significance and management of donor‐specific antibodies (DSA) against human leukocyte antigen (HLA) remain undefined. The aim of this single‐center study was to investigate the occurrence of DSA, their clinical impact on predictors for and protectors against DSA. Patients and Methods We compared anti‐HLA DSA (cutoff for mean fluorescence intensity (MFI) ≥ 1000), clinical and laboratory results and outcome in a routine (RG, n = 142, standard DSA testing) and a hepatopathy group (HG, n = 19, DSA testing following indeterminate hepatopathy) in 161 pLT patients, treated 2000–2021, retrospectively. Results 40% of RG and 32% of HG patients were DSA+ (39% of all patients, of which 13% with antibody‐mediated rejection [AMR]). Most frequent DSA subtypes were HLA‐DQ3, ‐DQ1, ‐DQ2 in RG and HLA‐DQ2, ‐DR15 in HG. MFI was higher for anti‐HLA II DSA (15 257 DSA+ vs. 5500 DSA−, p = 0.003), especially with AMR (21 000 DSA+ with AMR vs. 14 584 DSA+ without AMR, p = 0.042). Predictors for DSA included age at pLT, re‐pLT, and cystic fibrosis. Living donation and cold ischemia time <8 h appeared to offer protection. Graft survival was poorer with DSA (RG 78% DSA+ vs. 97% DSA−, p = 0.018, HG 67% DSA+ vs. 100% DSA−, p = 0.0007). Patient survival was 97% for the entire cohort. Conclusions DSA were detectable in 39% and associated with AMR in 13% of children post‐pLT in addition to worse graft survival in all patients. Patient survival of 97% was not influenced. Potential DSA and predictors and protectors were identified. Therefore, DSA diagnostics are recommended after pLT.