IMPORTANCE Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts.OBJECTIVE To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTSThis multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURESThe primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant. RESULTSOf 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant.CONCLUSIONS AND RELEVANCE This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use.
The 28-day and 90-day mortality were significantly decreased for transplant recipients compared with nontransplant patients. These findings suggest that the immunosuppression associated with transplantation may provide a survival advantage to transplant recipients with sepsis through modulation of the inflammatory response.
Kidney‐alone transplant (KAT) candidates may be disadvantaged by the allocation priority given to multi‐organ transplant (MOT) candidates. This study identified potential KAT candidates not receiving a given kidney offer due to its allocation for MOT. Using the Organ Procurement and Transplant Network (OPTN) database, we identified deceased donors from 2002 to 2017 who had one kidney allocated for MOT and the other kidney allocated for KAT or simultaneous pancreas–kidney transplant (SPK) (n = 7,378). Potential transplant recipient data were used to identify the “next‐sequential KAT candidate” who would have received a given kidney offer had it not been allocated to a higher prioritized MOT candidate. In this analysis, next‐sequential KAT candidates were younger (p < .001), more likely to be racial/ethnic minorities (p < .001), and more highly sensitized than MOT recipients (p < .001). A total of 2,113 (28.6%) next‐sequential KAT candidates subsequently either died or were removed from the waiting list without receiving a transplant. In a multivariable model, despite adjacent position on the kidney match‐run, mortality risk was significantly higher for next‐sequential KAT candidates compared to KAT/SPK recipients (hazard ratio 1.55, 95% confidence interval 1.44, 1.66). These results highlight implications of MOT allocation prioritization, and potential consequences to KAT candidates prioritized below MOT candidates.
Inferior outcomes are consistently observed for recipients of liver retransplantation (re-LT) versus recipients of primary transplants. Few studies have examined the incidence and impact of biliary complications (BCs) on outcomes after re-LT. The aim of this study was to compare patient and graft survival for re-LT recipients with BCs (BC 1 ) and re-LT recipients without BCs (BC 2 ). Additional aims were to determine the impact of biliary reconstruction on the incidence of BCs and to identify risk factors for BCs after re-LT. A single-center, retrospective analysis of all re-LT recipients over a decade was performed. Univariate analyses were performed, and survival was compared with the log-rank method. A multivariate Cox regression analysis was performed to determine independent predictors of death and graft failure. The BC rate was 20.9% (n 5 23) for 110 re-LT cases. The average follow-up was 55 months. The survival rates for BC 2 recipients at 3 months and 1, 3, and 5 years were 95.3%, 91.7%, 85.4%, and 80.9%, respectively, whereas BC 1 patients had survival rates of 64.3%, 49.7%, 34.8%, and 29.8%, respectively (P < 0.001, log-rank). The graft survival rates at 3 months and 1, 3, and 5 years were 92.0%, 88.5%, 82.4%, and 78.0%, respectively, for the BC 2 group and 60.9%, 43.5%, 30.4%, and 26.1%, respectively, for the BC 1 group (P < 0.001, log-rank). BCs, a length of stay 12 days, and donor age were strongly associated with death and graft failure in a regression analysis, whereas retransplant indications other than chronic rejection and recurrent disease also affected graft failure. In conclusion, BCs significantly affected both patient and graft survival, with an increased risk of death and graft loss among BC 1 It has been well established that both graft survival and patient survival are inferior for multitransplant patients versus primary LT patients. A further examination of data from the Scientific Registry of Transplant Recipients for the same period reveals that the graft survival rates at 1, 3, and 5 years were 82.6%, 74.2%, and 56.0%, respectively, for re-LT and 92.4%, 86.1%, and 69.9%, respectively, for primary grafts. In addition, the annual death rate per 1000 patient years has been 2 to 3 times higher for recipients of multiple LT procedures versus recipients of primary transplants over the past 9 years. Numerous authors have looked at causal relationships between complications and mortality in the re-LT population.2-7 To date, however, few authors have examined the Abbreviations: BC, biliary complication; CI, confidence interval; HR, hazard ratio; LT, liver transplantation; MELD, Model for EndStage Liver Disease; re-LT, liver retransplantation.Address reprint requests to C.
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