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Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation.

ABSTRACT: Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p < 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%; p = 0.692; hepatic 3.5% vs. 2.7%, p = 0.788; malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications.

SUBMITTER: Unlu S

PROVIDER: S-EPMC7763868 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation.

Ünlü Sinem S Lachmann Nils N Jara Maximilian M Ritschl Paul Viktor PV Wiering Leke L Eurich Dennis D Denecke Christian C Biebl Matthias M Chopra Sascha S Gül-Klein Safak S Schöning Wenzel W Schmelzle Moritz M Reinke Petra P Tacke Frank F Pratschke Johann J Öllinger Robert R Dziodzio Tomasz T

Journal of clinical medicine 20201209 12

Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-n ...[more]

PMID: 33317012

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Project description:Background and objectivesThe prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation.Design, setting, participants, & measurementsThe outcome of 4233 consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays. Using these screening results, DSA against HLA-A, -B, -C, -DRB1 and -DQB1 were determined. Data on clinical outcome and possible covariates were collected retrospectively.ResultsPretransplant DSA were associated with lower overall graft survival, with a hazard ratio of 2.53 for living donation (95% confidence interval [95% CI], 1.49 to 4.29; P<0.001) and 1.59 for deceased donation (95% CI, 1.21 to 2.11; P=0.001). ABO-incompatible transplantation was associated with worse graft survival (hazard ratio, 2.09; 95% CI, 1.33 to 3.27; P=0.001) independent from DSA. There was no difference between DSA against class 1, class 2, or both. Stratification into DSA <3000 medium fluorescence intensity (MFI) and DSA ≥3000 MFI resulted in overlapping survival curves. Therefore, separate analyses were performed for 3-month and long-term graft survival. Although DSA <3000 MFI tended to be associated with both lower 3-month and long-term transplant survival in deceased donation, DSA ≥3000 MFI were only associated with worse long-term transplant survival in deceased donation. In living donation, only strong DSA were associated with reduced graft survival in the first 3 months, but both weak and strong DSA were associated with reduced long-term graft survival. A higher incidence of antibody-mediated rejection within 6 months was only associated with DSA ≥3000 MFI.ConclusionsPreformed DSA were associated with an increased risk for graft loss in kidney transplantation, which was greater in living than in deceased donation. Even weak DSA <3000 MFI were associated with worse graft survival. This association was stronger in living than deceased donation.

Project description:Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab (N = 36) in combination with thymoglobulin (N = 20) or anti-IL2 receptor antibody (N = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P = 0.55 and P = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients (P = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients (P = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization (P < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and de novo DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without de novo DSA had an AMR rate of 18% without graft loss while one patient lost her graft without signs of AMR. Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss.

Project description:BackgroundLiving donor liver transplantation (LDLT) provides an alternative to deceased donor liver transplantation (DDLT) for patients with end-stage liver disease in the circumstance of scarcity of deceased grafts. However, the outcomes of LDLT remain controversial.MethodA systematic review and meta-analysis were performed to compare the outcomes of LDLT with DDLT. Twelve outcomes were assessed.ResultsThirty-nine studies involving 38563 patients were included. LDLT was comparable in red blood cell transfusion, perioperative mortality, length of hospital stay, retransplantation rate, hepatitis C virus recurrence rate, and hepatocellular carcinoma recurrence rate with DDLT. Cold ischemia time was shorter and duration of recipient operation was longer in LDLT. Postoperative intra-abdominal bleeding rate occurred less frequently in LDLT recipients (odds ratio (OR) = 0.64, 95%confidence interval (CI) = 0.46 - 0.88, P = 0.006), but this did not decrease the perioperative mortality. LDLT was associated with significantly higher biliary (OR = 2.23, 95%CI = 1.59 - 3.13, P < 0.00001) and vascular (OR = 2.00, 95%CI = 1.31 - 3.07, P = 0.001) complication rates and better overall survival (OS) (1 year: OR = 1.32, 95%CI = 1.01 - 1.72, P = 0.04; 3 years: OR = 1.39, 95%CI = 1.14 - 1.69, P = 0.0010; and 5 years: OR = 1.33, 95%CI = 1.04 - 1.70, P = 0.02). According to subgroup analysis, biliary complication rate and OS improved dramatically as experience increased, while vascular complication rate could not be improved because it was mainly caused by the difference of the donor type itself.ConclusionsLDLT remains a valuable option for patients in need of liver transplantation for it provides an excellent alternative to DDLT without compromising recipient outcomes. Further refinement in biliary and vascular reconstruction techniques and the accumulation of liver transplantation centers' experience are the key factors in expanding the application of LDLT.

Dataset Information

Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation.

Publications

Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation.

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