Donor-Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients

Levitsky, Josh; Kaneku, Hugo; Jie, Chunfa; Walsh, R. C.; Abécassis, Michaël; Tambur, Anat R.

doi:10.1111/ajt.13757

Cited by 58 publications

(54 citation statements)

References 30 publications

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“…This suggests that while CNI therapy may participate in the clearance of pfDSA, these antibodies did not appear to have an impact on outcomes. Together, these results add to the controversy about pfDSA as some reports have shown associations with liver allograft failure and early rejection when pfDSA are against HLA‐II antigens …”

Section: Discussionmentioning

confidence: 60%

Prevalence and Impact of De Novo Donor‐Specific Antibodies During a Multicenter Immunosuppression Withdrawal Trial in Adult Liver Transplant Recipients

et al. 2019

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Section: Discussionmentioning

confidence: 60%

Prevalence and Impact of De Novo Donor‐Specific Antibodies During a Multicenter Immunosuppression Withdrawal Trial in Adult Liver Transplant Recipients

et al. 2019

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“…These corroborative findings, which are consistent with results in other organs, may help to explain recent data demonstrating higher survival and less impact of donor specific antibodies in LDLT vs. DDLT recipients. 5, 6, 23 In regard to immune-mediated diseases, higher rejection rates in autoimmune hepatitis have led to recommendations for augmented immunosuppression. 7, 15, 22, 24 However, in A2ALL and SRTR cohorts, LT recipients with other immune-mediated liver disease (primary biliary cirrhosis, primary sclerosing cholangitis) had significantly increased risks, suggesting the need to maintain a higher level of immunosuppression in all immune-mediated diseases.…”

Section: Discussionmentioning

confidence: 99%

Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients

Levitsky

Goldberg

Smith

et al. 2017

Clinical Gastroenterology and Hepatology

192

162

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Background & Aims Acute rejection is detrimental to most transplanted solid organs, but is considered to be less of a consequence for transplanted livers. We evaluated risk factors for and outcomes after biopsy-proven acute rejection (BPAR) based on an analysis of a large national sample of recipients of liver transplants from living and deceased donors. Methods We analyzed data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) from 2003 through 2014 as the exploratory cohort and the Scientific Registry of Transplant Recipients (SRTR) from 2005 through 2013 as the validation cohort. We examined factors associated with time to first BPAR using multivariable Cox regression or discrete-survival analysis. Competing risks methods were used to compare causes of death and graft failure between recipients of living vs deceased donors. Results At least 1 BPAR episode occurred in 239/890 recipients in A2ALL (26.9%) and 7066/45,423 recipients in SRTR (15.6%). In each study, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% CI, 0.43–0.76 and SRTR HR, 0.78; 95% CI, 0.66–0.91) (P<.001) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each study, BPAR was associated with significantly higher risks of graft failure and death. The risks were highest in the 12 month post-BPAR period in patients whose first episode occurred more than 1 year after liver transplantation. The HRs for graft failure were 6.79 in A2ALL (95% CI, 2.64–17.45) and 4.41 in SRTR (95% CI, 3.71–5.23). The HRs for death were 8.81 in A2ALL (95% CI, 3.37–23.04) and 3.94 in SRTR (95% CI, 3.22–4.83). In analyses of cause-specific mortality, associations were observed for liver-related (graft failure) causes of death but not for other causes. Conclusions Contrary to previous data, acute rejection after liver transplant is associated with significantly increased risk of graft failure, all-cause mortality and graft failure-related death. LDLT from a biologically related donor is associated with decreased risk of rejection.

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“…Levitsky et al . examined the association between DSAs and survival after DDLT and LDLT, and reported that preformed DSAs were associated with a higher graft failure rate only after DDLT . However, there was survival selection bias as the vast majority of the post‐transplant samples were available only at or after 3 months.…”

Section: Discussionmentioning

confidence: 99%

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

Tamura

Tohyama

Watanabe

et al. 2019

Hepatology Research

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Aim The impact of donor‐specific anti‐human leukocyte antigen (HLA) antibodies (DSAs) on living donor liver transplantation (LDLT) is unclear. The aim of this study was to investigate the association between DSAs and short‐term outcomes in LDLT recipients, and to clarify the clinical impact of DSAs. Method Anti‐HLA antibodies were screened in preoperative serum samples taken from 40 liver transplant recipients at Ehime University (Toon, Japan) between August 2001 and July 2015. Screening was carried out using the Flow‐PRA method, and DSAs were detected in anti‐HLA antibody‐positive recipients using the Luminex single‐antigen identification test. A mean fluorescence intensity of 1000 was used as the cut‐off for positivity. We retrospectively reviewed the clinical courses of patients who were DSA‐positive to elucidate early clinical manifestations in LDLT recipients. Results Fifteen (12 female and 3 male) patients (38%) had anti‐HLA antibodies. Eight of the 15 anti‐HLA antibody‐positive patients were positive for DSAs, and all were women. The 90‐day survival rate of DSA‐positive patients (50%) was significantly lower than that of DSA‐negative patients (84.4%) (0.0112; Wilcoxon test). On univariate analysis, the DSA‐positive rate was significantly higher in the 90‐day mortality group. Postoperatively, the incidence of acute cellular rejection was higher in DSA‐positive than DSA‐negative patients. Thrombotic microangiopathy developed only in DSA‐positive patients. We found no relationship between DSA status and bile duct stricture. Conclusion Preformed DSAs could be associated with elevated 90‐day mortality in LDLT recipients. Further large‐scale studies are required to verify the risk associated with DSAs in LDLT.

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Donor-Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients

Cited by 58 publications

References 30 publications

Prevalence and Impact of De Novo Donor‐Specific Antibodies During a Multicenter Immunosuppression Withdrawal Trial in Adult Liver Transplant Recipients

Prevalence and Impact of De Novo Donor‐Specific Antibodies During a Multicenter Immunosuppression Withdrawal Trial in Adult Liver Transplant Recipients

Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients

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

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