Preformed donor‐specific HLA antibodies are associated with increased risk of early mortality after liver transplantation

Abstract

There is limited evidence for a negative impact of preformed, donor-specific HLA antibodies (DSA) identified by cross-matching on outcomes after liver transplantation. Three recent studies have suggested an association between preformed DSA detected by Luminex and reduced graft or recipient survival in liver transplant cohorts with a high prevalence of hepatitis C. This study investigated the impact of preformed DSA identified by Luminex in the Scottish liver transplant population. All recipients of liver transplants in Scotland between 2007 and 2015 with samples available for day of transplant antibody testing and donor HLA typing were included (n=459); 96% of the cohort were white and 19% had a primary diagnosis of hepatitis C. The median follow-up time was 36 months. Preformed DSA were detected in 88 recipients. In multivariate analysis, preformed DSA with a median fluorescent intensity ≥10 000 were associated with recipient mortality at 1 year. There was no association between DSA and overall graft or recipient survival. This study adds to the growing body of evidence supporting a detrimental impact of preformed, high-level DSA in a subset of liver transplant recipients by identifying an association in an ethnically and demographically distinct liver transplant population.

Preformed donor‐specific antibodies do not affect the 1‐year allograft survival in living donor liver transplantation

“…Yoshizawa et al reported that the presence of HLA class I DSAs with MFI > 10000 had a significant negative effect on the clinical outcome of patients with preformed DSAs in a cohort of 18 patients who underwent LDLT. McCaughan et al also reported that there was a significant association between preformed DSAs with a cumulative MFI > 10000 and recipient survival within the first year after LT. However, when we divided the groups with DSAs with MFI > 10000 and analyzed their results, there was no significant effect attributed to preformed DSAs in our study.…”

Outcome of Liver Transplant Patients With Preformed Donor‐Specific Anti–Human Leukocyte Antigen Antibodies

“…However, few data concerning the medium‐term and longterm impact of pDSAs exist. It has been suggested that pDSAs can reduce patient survival rates, induce early graft rejections, accelerate liver fibrosis, and, in a few highly sensitized cases, induce early graft failure …”

Preformed donor‐specific antibodies are associated with 90‐day mortality in living‐donor liver transplantation

“…reported the first case of AMR due to DSAs that fulfilled all humoral alloinjury criteria in an ABO‐compatible setting . Thereafter, important reports on the results of DDLT in patients with DSAs have been published from various centers . In those studies, detection of DSAs by Luminex, particularly with high MFI, was associated with rejection and impaired graft survival .…”

“…Patients with DSAs >10 000 MFI, C1q or C3‐binding DSAs, multiple DSAs, or DSAs together with a condition involving complement activation (such as an inflammatory disease) are assumed to be at elevated risk for AMR. In such high‐risk patients, we first consider changing the donor in cases of LDLT.…”

“…[8][9][10][11]30,31 In those studies, detection of DSAs by Luminex, particularly with high MFI, was associated with rejection and impaired graft survival. [8][9][10][11]30,31 In a study of LDLT, Song et al in Korea reported that recipients with multiple DSAs tended to have more acute rejection episodes and lower graft survival rates than did DSA-negative patients. 23 Yoshizawa et al reported that 7 of 11 LDLT recipients strongly positive (MFI >10 000) for DSAs against HLA class I died within 4 months.…”