Prevalence, Risk Factors, and Impact of Donor‐Specific Alloantibodies After Adult Liver Transplantation

Abstract

The incidence and impact of anti-human leukocyte antigen donor-specific alloantibodies (DSAs) developing after liver transplantation (LT) remains controversial and not extensively studied. The aim of the present study was to assess the incidence of DSAs, to identify risk factors for the development of DSAs, and to understand the impact of DSAs in a large population of adult LT recipients. This single-center retrospective study included all adult patients who underwent a first LT between 2000 and 2010 in our center. The study population mainly consisted of male patients, the mean age was 52.4 years, and the main indication was alcoholic cirrhosis (54.1%). From the 297 patients included in the cross-sectional study, 14 (4.7%) had preformed DSAs, and 59 (19.9%) presented de novo DSAs (12.2% at 1 year, 13.4% at 5 years, and 19.5% at 10 years). Multivariate analysis found that female donor sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.12-2.01; P = 0.01) and delay between LT and DSA screening (HR, 1.10; 95% CI, 1.01-1.20; P = 0.03) were associated with occurrence of de novo DSAs. From the 190 patients included in the subgroup longitudinal analysis, exposure to tacrolimus (mean trough level during the periods 0-2 years and 0-3 years) was significantly lower for patients having DSAs at 5 years. Concerning histology, only acute rejection (P = 0.04) and portal fibrosis ≥2 (P = 0.02) were more frequent at 1 year for patients with DSAs. Patient survival and graft survival were not significantly different according to the presence or not of DSAs at 1 year. Among the 44 patients who had de novo or persistent preformed DSAs, the diagnosis of antibody-mediated rejection was made in 4 (9.1%) patients after 1, 47, 61, and 74 months following LT. In conclusion, the results of the present study suggest that DSAs are observed in a minority of LT adult patients, with limited overall impact on graft and patient outcome.

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

“…In our cohort, only 10 patients had criteria for acute AMR, as previously described . The low incidence of acute AMR even in a cohort of at‐risk recipients with pDSAs is in line with previously published studies . Nonetheless, because the C4d staining was not performed in patients with histological features of cellular rejection and because T‐cell mediated rejection (TCMR) and AMR histological features may overlap, we may have missed a few cases.…”

Non-invasive screening for subclinical liver graft injury in adults via donor-specific anti-HLA antibodies

“…While this was the first analysis of the predictive value of CK18 levels for graft injury after liver transplantation beyond hepatitis C 28 , the association of DSA with graft injury in general is a well described phenomenon 4,12,14,16,18,20,21 . However, we are not aware of another study with a specific focus on non-invasive capacities of both parameters in comparison to the routine blood markers to detect subclinical graft injury in adults.…”

Impact of low tacrolimus exposure and high tacrolimus intra-patient variability on the development of de novo anti-HLA donor-specific antibodies in kidney transplant recipients

“…More recently, Del Bello et al described that at a cutoff CV of >35% the odds ratio for developing dnDSA within the first 2 years posttransplantation was 4.83 (p = 0.01) and at a cutoff CV of >40% the odds ratio increased to 9.73 (p = 0.01) [79]. However, dnDSA and a high tacrolimus IPV seem to have a limited overall impact on graft and patient outcome after liver transplantation [80,81].…”