Prevalence, Incidence and Risk Factors for Donor-Specific Anti-HLA Antibodies in Maintenance Liver Transplant Patients

Abstract

Although large retrospective studies have identified the presence of donor-specific antibodies (DSAs) to be a risk factor for rejection and impaired survival after liver transplantation, the long-term predicted pathogenic potential of individual DSAs after liver transplantation remains unclear. We investigated the incidence, prevalence and consequences of DSAs in maintenance liver transplant (LT) recipients. Two hundred sixtyseven LT recipients, who had undergone transplantation at least 6 months previously and had been screened for DSAs at least twice using single-antigen bead technology, were included and tested annually for the presence of DSAs. At a median of 51 months (min-max: 6-220) after an LT, 13% of patients had DSAs. At a median of 36.5 months (min-max: 2-45) after the first screening, 9% of patients have developed de novo DSAs. The sole predictive factor for the emergence of de novo DSAs was retransplantation (OR 3.75; 95% CI 1.28-11.05, p ¼ 0.025). Five out of 21 patients with de novo DSAs (23.8%) developed an antibody-mediated rejection. Fibrosis score was higher among patients with DSAs. In conclusion, monitoring for the development of DSAs in maintenance LT patients is useful in case of graft dysfunction and to identify patients with a high risk of developing liver fibrosis.

Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

“…No increased risk in sensitization has been reported in patients without corticosteroids in a prospective single-center study on kidney transplantation 58 and two retrospective studies on liver transplantation. 59,60 These encouraging results are also supported by the conclusions in the work by Delgado et al, 61 which randomized 37 recipients of kidney transplants with ATG induction, tacrolimus, and mycophenolic acid (MPA) for corticosteroid withdrawal 1 week post-transplantation. Delgado et al 61 did not observe any difference in dnDSA incidence at 5 years.…”

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients

“…20 However, knowledge of the pathological impact of DSAs is still evolving, particularly with regard to the impact of DSAs postliver transplantation. [39][40][41] Furthermore, patient survival can be improved by attention to modifiable risk factors for CVD and cerebrovascular disease, some infections and some cancers. 34 The development of new-onset diabetes posttransplant (NODAT) is also associated with reduced patient and graft survival, as well as an increased risk of infections and CVD.…”

“…39 While DSAs are now identified as a risk factor for graft rejection and are detrimental to patient survival, the full impact of DSAs postliver transplant remains to be fully elucidated. 41 For clarity, this section describes evidence for the impact of DSAs in kidney transplantation and current knowledge on the impact of DSAs in liver transplantation.…”

Advancing Transplantation

“…Several groups have reported an increased incidence of occult fibrosis in the presence of posttransplant DSA. [109][110][111][112][113][114][115][116] In pediatric liver transplant, DSA+ versus DSA− patients are more likely to develop advanced fibrosis on protocol biopsy. 110 DSA+ versus DSA− HCV viremic patients had a tripling in their risk of advanced fibrosis by 1 year posttransplant.…”

“…112 In patients >6 months posttransplant, 9% of DSA−patients developed de novo DSA, one quarter experienced acute AMR, and even HCV-negative patients with DSA (versus without) had more advanced fibrosis. 109 Diagnostic criteria for chronic AMR have recently been proposed for the identification of liver allograft recipients with DSA at higher risk for allograft loss. 117 When attempting to identify DSA+ patients at highest risk for overt problems, several factors have been elucidated.…”