Association of post‐transplant donor‐specific HLA antibody with liver graft fibrosis during long‐term follow‐up after pediatric liver transplantation

Abstract

The aim of this study was to evaluate the significance of post-transplant DSA as a predictor of liver fibrosis during long-term follow-up after pediatric LT. We evaluated the histological findings in 18 LT recipients who underwent liver biopsy after DSA screening. Liver fibrosis was scored based on the METAVIR fibrosis staging. Patients were divided into 2 groups based on histological findings, and clinical characteristics among patients with liver fibrosis were assessed. Of 18 patients, 7 were included in the fibrosis group. No significant between-group differences were found regarding peritransplant characteristics, including age, sex, primary disease, ABO incompatibility, and immunosuppressive regimen. Episodes of acute rejection and non-adherence to immunosuppressive drugs were comparable between both groups. The MFI for anti-DR DSA and positive rate were significantly higher in the fibrosis group (1655 vs 216; P = .019, 86% vs 27%; P = .012, respectively). MFI for anti-DQ DSA was higher in the fibrosis group, but non-significantly (2052 vs 384; P = .46). Post-transplant anti-DR DSA is associated with graft fibrosis during long-term follow-up. This finding seems useful for the implementation of valid histological examinations of liver grafts for patients with higher MFI, especially for anti-DR DSA, after pediatric LT.

De novo HLA Class II antibodies are associated with the development of chronic but not acute antibody‐mediated rejection after liver transplantation – a retrospective study

“…[32] and Tokodai et al . [33], who reported that inflammation and fibrosis in paediatric liver transplant biopsies, which are considered as morphological features of chronic rejection, were related to the presence of circulating de novo DSA, especially DSA to HLA Class II antigens. It can be speculated about the reason why non‐DSA to HLA Class II antigens in our study predicted an increased risk for the development of chronic AMR.…”

Recurrence of Hepatocellular Carcinoma After Liver Transplantation is Associated with Episodes of Acute Rejections

“…40 In pediatric patients an association between antibodymediated AR and progress of graft fibrosis leading to liver graft damage after LT was reported. 41,42 Furthermore, development and severity grade of liver fibrosis after LT is discussed as a potential predictor for death and graft loss in recipients. 43 The chronically inflamed environment may promote carcinogenesis and may contribute to the increased frequency of tumor recurrence.…”

Paediatric liver transplantation in Australia and New Zealand: 1985‐2018

“…41 Possible antibody-mediated graft dysfunction is being increasingly identified with HLA donor-specific antibody measurement. 42 Other well-known complications include renal dysfunction and risks of malignancy and/or post-transplant lymphoproliferative disease. Neurodevelopmental and quality of life issues are also being addressed.…”

“…Protocol biopsies have revealed chronic graft dysfunction, even with normal liver function tests, 40 but also children with normal biopsies who might be considered for complete immunosuppression withdrawal 41 . Possible antibody‐mediated graft dysfunction is being increasingly identified with HLA donor‐specific antibody measurement 42 . Other well‐known complications include renal dysfunction and risks of malignancy and/or post‐transplant lymphoproliferative disease.…”