Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation

Abstract

BACKGROUND In a previous paper, we reported a high prevalence of donor-specific antibody (DSA) in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort. AIM To clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients. METHODS We performed a retrospective analysis of 123 pediatric liver transplantation (LT) recipients who participated in yearly follow-ups including Luminex testing for DSA at our center. The cohort was split into two groups according to the DSA status (DSA-positive n = 54, DSA-negative n = 69). Groups were compared with regard to liver function, biopsy findings, graft survival, need for re-LT and immunosuppressive medication. RESULTS DSA-positive pediatric patients showed a higher prevalence of chronic rejection ( P = 0.01), fibrosis ( P < 0.001) and re-transplantation ( P = 0.018) than DSA-negative patients. Class II DSAs particularly influenced graft survival. Alleles DQ2, DQ7, DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis. Mean fluorescence intensity levels and DSA number did not impact graft survival. Previous episodes of chronic rejection might lead to DSA development. CONCLUSION DSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT. Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibody-mediated rejection improved early identification of patients at risk of graft loss.

Protocol Biopsies in Pediatric Liver Transplantation Recipients Improve Graft Histology and Personalize Immunosuppression

“…In another study of OLT recipients, the prevalence of DSAs was high (48%), and the incidence of bridging fibrosis or cirrhosis was 88% in DSA-positive patients versus 17% in DSA-negative patients (33). Accordingly, the most recently published findings of our center confirmed that the amount of fibrosis and rejection is higher in patients with DSAs (34). In the present study, DSA-positive patients showed a significantly higher Metavir fibrosis score than DSA-negative patients.…”

Basiliximab Induction and Postoperative Steroid-free Immunosuppression With Tacrolimus in Pediatric Liver Transplantation: A Randomized Clinical Trial

“…A recent study showed that the positivity of DSA is related to chronic antibody-mediated rejection as well as compromised long-term survival rate. 20 About the effect of steroid in DSA, a retrospective analysis of 749 liver transplant recipients showed that the risk of de novo DSA was reduced in the presence of steroid therapy in univariate but not in multivariate analysis. 21 Similarly, in a retrospective analysis of 232 liver transplant patients, de novo DSA was tested annually, but the multivariate analysis did not show an association between steroid therapy and de novo DSA.…”

Asymptomatic Allograft Fibrosis in Pediatric Liver Transplantation: Potential Clinical Implications

“…6 In fact, an association between DSA and fibrosis has been well documented. [7][8][9] However, cAMR is a diagnosis of exclusion with an estimated prevalence of 8% to 15% in recipients who present with persistent or de novo DSAs, specially targeting HLA class II. 10 Although cAMR may be an important contributor, its relatively low prevalence makes it difficult to explain the high prevalence of allograft fibrosis.…”