Key Points Question Can oxygenated portable normothermic perfusion of deceased donor livers for transplant improve outcomes compared with the current standard of care using ischemic cold storage? Findings In this multicenter randomized clinical trial of 300 recipients of liver transplants with the donor liver preserved by either normothermic perfusion or conventional ischemic cold storage, normothermic machine perfusion resulted in decreased early liver graft injury and ischemic biliary complications and greater organ utilization. Meaning In this study, portable normothermic oxygenated machine perfusion of donor liver grafts resulted in improved outcomes after liver transplant and in more livers being transplanted.

Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant

OBJECTIVE The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD). BACKGROUND HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT). METHODS Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD). RESULTS Demographics were equally distributed between both groups [donor age: 72 (IQR: 59-78) years, recipient age: 62 (IQR: 55-65) years, labMELD: 15 (IQR: 9-25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221-828) vs 796 (IQR: 477-1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12-56) vs 52 (IQR: 35-98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4-8) vs 8 (IQR: 5-18) days, P = 0.045; 20 (IQR: 16-27) vs 36 (IQR: 23-62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314). CONCLUSION This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation.

Hypothermic Oxygenated Machine Perfusion (HOPE) Reduces Early Allograft Injury and Improves Post-Transplant Outcomes in Extended Criteria Donation (ECD) Liver Transplantation from Donation After Brain Death (DBD): Results from a Multicenter Randomized Controlled Trial (HOPE ECD-DBD)

Transplantation of a human liver following 3 days of ex situ normothermic preservation

http://www.amjtransplant.org/article/S1600613522082478/pdf

Sequential hypothermic and normothermic machine perfusion enables safe transplantation of high‐risk donor livers

In donation after circulatory death (DCD), (thoraco)abdominal regional perfusion (RP) restores circulation to a region of the body following death declaration. We systematically reviewed outcomes of solid organ transplantation after RP by searching PubMed, Embase, and Cochrane libraries. Eighty-eight articles reporting on outcomes of liver, kidney, pancreas, heart, and lung transplants or donor/organ utilization were identified. Meta-analyses were conducted when possible. Methodological quality was assessed using National Institutes of Health (NIH)-scoring tools. Case reports (13/88), case series (44/88), retrospective cohort studies (35/88), retrospective matched cohort studies (5/88), and case-control studies (2/88) were identified, with overall fair quality. As blood viscosity and rheology change below 20 °C, studies were grouped as hypothermic (HRP, ≤20 °C) or normothermic (NRP, >20 °C) regional perfusion. Data demonstrate that RP is a safe alternative to in situ cold preservation (ISP) in uncontrolled and controlled DCDs. The scarce HRP data are from before 2005. NRP appears to reduce post-transplant complications, especially biliary complications in controlled DCD livers, compared with ISP. Comparisons for kidney and pancreas with ISP are needed but there is no evidence that NRP is detrimental. Additional data on NRP in thoracic organs are needed. Whether RP increases donor or organ utilization needs further research.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/tri.14121

A systematic review and meta-analyses of regional perfusion in donation after circulatory death solid organ transplantation.

Background Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine ...

https://www.nejm.org/doi/suppl/10.1056/NEJMoa2031532/suppl_file/nejmoa2031532_data-sharing.pdf

Hypothermic Machine Perfusion in Liver Transplantation — A Randomized Trial

Diagnostic performance of preoperative CT in differentiating between benign and malignant origin of suspicious gallbladder lesions

Background and methods Treatment strategies for pancreatic cancer patients are made by a multidisciplinary team (MDT) board. We aimed to assess intra-observer variance at MDT boards. Participating units staged, assessed resectability, and made treatment allocations for the same patients as they did two years earlier. We disseminated clinical information and CT images of pancreatic cancer patients judged by one MDT board to have nonmetastatic pancreatic cancer to the participating units. All units were asked to re-assess the TNM stage, resectability, and treatment allocation for each patient. To assess intra-observer variance, we computed %-agreements for each participating unit, defined as low ( 75%) agreement. Results Eighteen patients were re-assessed by six MDT boards. The overall agreement was moderate for TNM-stage (ranging from 50%-70%) and resectability assessment (53%) but low for treatment allocation (46%). Agreement on resectability assessments was low to moderate. Findings were similar but more pronounced for treatment allocation. We observed a shift in treatment strategy towards increasing use of neoadjuvant chemotherapy, particularly in patients with borderline resectable and locally advanced tumors. Conclusions We found substantial intra-observer agreement variations across six different MDT boards of 18 pancreatic cancer patients with two years between the first and second assessment.

Jules J.G. Slangen

Papers

Hypothermic Machine Perfusion in Liver Transplantation — A Randomized Trial

Diagnostic performance of preoperative CT in differentiating between benign and malignant origin of suspicious gallbladder lesions

Intra-observer agreements in multidisciplinary team assessments of pancreatic cancer patients