Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant The OCS Liver PROTECT Randomized Clinical Trial

• Type of Material: Article
• Authors: James F Markmann, Massachusetts General Hospital; Marwan S Abouljoud, Henry Ford Transplant Institute, Detroit; Mark R Ghobrial, Houston Methodist; Chandra S Bhati, Virginia Commonwealth University; Shawn J Pelletier, University of Virginia; Amy D Lu, Tampa General; Shane Ottmann, Johns Hopkins, Baltimore; Tarunjeet Klair, UT Health Science Center; Corey Eymard, University of Tennessee; Garrett R Roll, UCSF, San Francisco; Joseph Magliocca, Emory University; Timothy L Pruett, University of Minnesota, Minneapolis; Jorge Reyes, University of Washington; Sylvester M Black, Ohio State University; Christopher L Marsh, Scripps Clinic and Scripps Green Hospital; Gabriel Schnickel, University of California San Diego; Milan Kinkhabwala, Montefiore Medical Center; Sander S Florman, Mount Sinai Health System; Shaheeed Merani, University of Nebraska Medical Center; Anthony J Demetris, University of Pittsburgh; Shoko Kimura, Massachusetts General Hospital; Michael Rizzari, Henry Ford Transplant Institute, Detroit; Ashish Saharia, Houston Methodist; Marlon Levy, Virginia Commonwealth University; Avinash Agarwal, University of Virginia; Francisco G Cigarroa, UT Health Science Center; James D Eason, University of Tennessee; Shareef Syed, UCSF, San Francisco; Kenneth W Washburn, Ohio State University; Justin Parekh, University of California San Diego; Jang Moon, Mount Sinai Health System; Alexander Maskin, University of Nebraska; Heidi Yeh, Massachusetts General Hospital; Parsia A Vagefi, University of Texas Southwestern Medical Center; Malcolm P MacConmara, University of Texas Southwestern Medical Center
• Language: English
• Date: 2022-03-01
• Publisher: AMER MEDICAL ASSOC
• Publication Version: Final Published Version
• Copyright Statement: 2022 Markmann JF et al. JAMA Surgery.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1001/jamasurg.2021.6781
• Title of Journal or Parent Work: JAMA SURGERY
• Volume: 157
• Issue: 3
• Start Page: 189
• End Page: 198
• Grant/Funding Information: This study was supported by TranMedics Inc.
• Keywords: Surgery; Life Sciences & Biomedicine; ALLOGRAFTS; DONATION; ORGAN PRESERVATION; INJURY; BIOPSIES; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

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 Participants: This 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 Measures: The 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. Results: Of 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02522871.