Liver graft injury caused by de novo donor-specific HLA antibodies in pediatric liver transplant recipients with low, moderate, and high immunologic risk

Abstract

Background: This study investigated the association between different risk levels of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) and liver graft injury after liver transplantation in pediatric patients.

Methods: This retrospective cohort study enrolled 130 patients after liver transplantation. Subjects were divided into the following 4 groups according to the mean fluorescence intensity (MFI) of dnDSAs: high risk group(MFI ≥10,000), medium risk group(4000 ≤ MFI <10,000), low risk group(500 ≤ MFI <4000), and negative group(<500). Liver function indices were examined along with liver puncture biopsy，and the relationship between dnDSA risk level and liver injury after transplantation was assessed.

Results: Pediatric liver transplant recipients showed significant differences in liver function (ALT, AST, GGT and Bilirubin) according to dnDSA risk level (P < 0.05), and no differences in cumulative incidences of rejection (P = 0.413) and liver fibrosis (P = 0.978) were observed among the number of dnDSAs group. There were differences in the cumulative incidences of antibody-mediated rejection (AMR) (P = 0.001) and T cell-mediated rejection （TCMR） (P = 0.003) across risk groups. The cumulative incidences of TCMR and liver fibrosis (P = 0.0001) were higher in the low-risk group than in the other 3 groups. There were no differences in graft survival rate (P = 0.846) across risk groups.

Conclusion: DnDSAs in pediatric liver transplant recipients are associated with liver transplant rejection and fibrosis. The level of dnDSAs in low risk group should not be disregarded. Routine detection of dnDSAs has clinical utility for noninvasive risk stratification in this population.

Keywords: De novo donor-specific anti-HLA antibodies; Fibrosis; Liver graft injury; Pediatric liver transplantation; Rejection.