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Presence of Donor-Specific HLA Alloantibodies (DSAs) After Liver Transplantation is a Frequent Fact. Prospective Study in a Pilot Cohort

Díaz, Raquel1; Carbonell, Carlos1; Pérez, Leticia1; Romero, Mario1; Vicario, Jose Luis2; Rincón, Diego1; Bañares, Rafael1; Salcedo, Ma Magdalena1

doi: 10.1097/01.tp.0000520353.85938.90
210.1
Free

1Liver Transplant-Hepatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 2Regional Transfusion Centre, Regional Transfusion Centre, Madrid, Spain.

In recent years, DSAs have been related with liver injury, less survival of allografts and patients after liver transplantation (LT). However, the impact on the natural history after liver transplantation is not well understood. Aim: Analyse the prevalence of preformed DSAs and incidence of de novo DSAs analysis, in a cohort of patients with liver transplant, its risk factors and its medium-term impact. Methods: observational, prospective, unicentric study: adult patients’ cohort, who received a liver transplant between 2010–2011 in H.G.U. Gregorio Maranon, with homogeneous management and follow-up. Clinical evaluations and immunological determinations were registered immediately before LT, 3, 6, 12 months and 5 years after. DSAs presence, class (class I, II, anti-MICA) and mean fluorescence intensity were analysed. Follow-up was finished in August 2016. Thirty-three patients were included their mean age was 52 years old (SD 10.3) and 24.2% were women. The most common cirrhosis etiology was hepatitis C virus infection (45.5%) and the main reason for LT, decompensated cirrhosis (54.55%). Two patients did not finish the follow-up. Eight patients (24.2%) presented preformed DSAs (4 class I, 3 class II and 1 MICA). Preformed DSAs were related with age (45.5 vs 53.8 years old, p = 0.07) and women (50 vs 16%, p = 0.07). DSAs remained positive in 5/8 patients (62.5%) 6 month after LT; and in 4/8 (50%) of patients, 12 months after LT. 5 years after LT these DSAs were negative in all patients. There were no events related with preformed DSAs. Eight patients (24.2%) developed de Novo DSAs within the first year (1 class I DSAs, 5 class II, 1 MICA and 1 mixed class I and II). After 5 years, 2 out of these 8 patients remained positive for DSAs. There were no differences in age, sex, disease etiology or previous transfusions in patients with positive DSAs. Tacrolimus leves at 1, 3 and 6 months and basiliximab administration were the same in patients with positive DSAs. On the other hand, they received MMF in less proportion (37.5% vs. 60%, p = 0.42). During the 5-year follow up after LT, no relation between DSAs development and rejection risk, graft loss or death was found. In conclusion, preformed DSAs presence is a frequent, transitory fact, related with young age and gender; without apparent pathologic impact. In the same way, de novo DSAs development is a relatively frequent fact with possible pathogenic impact which still needs to be determined.

References:

1. JG, Demetris a J, Friedman LS, Gebel HM, Halloran PF, Kirk a D, O' Leary et al. The role of donor-specific HLA alloantibodies in liver transplantation. Am. J. Transplant. 2014 Apr;14(4):779–87

2. Leary JGO, Kaneku H, Demetris AJ, Marr JD, Shiller SM, Susskind BM, et al. Antibody-Mediated Rejection as a Contributor to Previously Unexplained Early Liver Allograft Loss. Liver Transplant. 2014;20:218–27

3. O' Leary JG, Gebel HM, Ruiz R, Bray R a, Marr JD, Zhou XJ, et al. Class II alloantibody and mortality in simultaneous liver-kidney transplantation. Am. J. Transplant. 2013 Apr;13(4):954–60

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