Current status of split liver transplantation using machine perfusion in the United States.

Background.Ex vivo machine perfusion (MP) has transformed organ preservation, offering significant benefits in liver transplantation (LT), particularly with high-risk donor grafts. However, adoption in the United States has been limited. We aimed to examine early adoption trends, surgeon perceptions, and barriers to implementing MP in the United States after Food and Drug Administration approval of MP platforms.Methods.A 23-question electronic survey was distributed to members of the American Society of Transplant Surgeons between October and November 2022, capturing attitudes and practices related to MP adoption. Responses from 96 surgeons representing 77 LT centers across 11 Organ Procurement and Transplantation Network regions were analyzed.Results.Forty-four respondents (48%) reported having an MP program at their institution. Adoption of MP was significantly more common in high-volume centers and those performing ≥20 donation after circulatory death (DCD) transplants annually (P < 0.001). MP utilization received strong support, with 88% endorsing its use for DCD liver allografts and 82% for donation after brain death allografts. Respondents cited MP’s ability to reduce ischemic cholangiopathy, enable graft repair, and facilitate viability assessment as key benefits. Normothermic MP was preferred for high-risk donor profiles, including DCD grafts, older donors, and steatotic livers, and was associated with an increased willingness to accept medically complex grafts compared with static cold storage. Barriers to MP utilization included program costs, personnel demands, and logistical complexities. Centers with higher proportions of privately insured patients were more likely to adopt MP. Despite these challenges, 84% of respondents expressed interest in future MP adoption.Conclusions.MP enhances graft utilization and outcomes, particularly for complex and high-risk donor livers, but widespread US adoption requires addressing financial and logistical barriers. Future efforts should focus on refining cost-effectiveness analyses, collaboration with organ procurement organizations and device companies, and developing standardized training to optimize MP integration and maximize its clinical impact on LT.

Addressing the challenges of split liver transplantation through technical advances. A systematic review

Hypothermic vs Normothermic Machine Perfusion in Liver Transplantation in the US: A Cohort Study.

Purpose of ReviewThis review describes the clinical evidence supporting hypothermic machine perfusion (HMP) application in liver transplant (LT).Recent FindingsSeveral randomized controlled trials (RCT) evaluating HMP, especially hypothermic oxygenated machine perfusion (HMP-O2 or HOPE/D-HOPE) have demonstrated decreased rate of early allograft dysfunction (EAD) and ischemic cholangiopathy (IC) in LT recipients. The clinical benefit associated with HMP has allowed increased utilization of extended criteria brain death liver grafts (ECD-DBD) and donation after circulatory death (DCD) liver grafts. Recently, a portable HMP-O2 circuit, which involves “oxygen pre-charging”, has been introduced in clinical practice in the United States of America (USA) to extend access and expand the portability of HMP. Additionally, measurement of flavin mononucleotide (FMN) levels during HMP allows intraoperative assessment of cumulative liver graft injury and prediction of post-LT function.SummaryGiven the robust clinical evidence supporting HMP application in clinical LT, stage is set for widespread adoption of HMP both at individual transplant centers and organ procurement organization level over the coming decade.

Machine perfusion (MP) for liver transplantation has become more widespread in the United States, but national studies on this growing practice are lacking. We investigated national use and outcomes of MP for liver transplantation. Adult (≥18 y) liver recipients transplanted between January 1, 2016 and September 30, 2023 in the United Network for Organ Sharing database were included. We used Cox regression to compare 1-y posttransplant recipient survival and all-cause graft failure by use of MP and performed subgroup analyses among circulatory death (DCD) and brain death (DBD) donors. Of 52 626 deceased donors with liver recovery, 1799 (3.5%) utilized MP. The proportion of all liver transplants using MP increased from 0.3% in 2016 to 15.5% in 2023. MP for DCD transplants increased from 0.8% in 2016 to 50.0% in 2023. Donors of MP grafts were older (47 [34-57] versus 42 [29-55] y, P < 0.001), had higher body mass indexes (28.3 [24.4-33.3] versus 27.3 [23.7-31.8] kg/m 2 , P < 0.001), and were more likely to be DCD (47.1% versus 9.3%, P < 0.001). Among DBD transplants, MP and non-MP DBD transplants had similar all-cause graft failure out to 1 y (adjusted hazards ratios, 1.12 [95% confidence interval, 0.87-1.43], P = 0.38). Among DCD transplants, MP recipients had improved survival out to 1 y (adjusted hazards ratios, 0.50 [95% confidence interval, 0.35-0.70], P < 0.001). MP use in liver transplantation is rapidly expanding and is associated with favorable outcomes compared with cold storage. MP is associated with increased posttransplant survival for DCD transplants, highlighting the potential for MP to expand utilization of DCD grafts.

Hypothermic Machine Perfusion of the Liver: Is It More Complex than for the Kidney?

Science, Medicine, and the Anesthesiologist

Rescue Thrombolysis

To the Editor: We read with great interest the article by Hessheimer et al titled “Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society.”1 The authors summarize relevant literature and provide guidelines for donation after circulatory death (DCD) liver transplant procurement on behalf of the International Liver Transplantation Society (ILTS). Our research group recently emphasized the variations in DCD organ procurement policies in the United States with a national organ procurement organization (OPO) survey.2 We discovered tremendous disparities across regions that frequently diverged from American Society for Transplant Surgeons (ASTS) recommendations for DCD procurement and the latest consensus in the literature. It is paramount to optimize graft utilization and outcomes to meet the high demand for transplantable organs and growing waitlist. We commend the authors for their important contributions. We highlight the role of asystolic wait time in DCD liver procurement that was not addressed in the work and provide observations on DCD liver transplant (LT) and machine perfusion (MP) from the United States. Our OPO survey underscored the variations in the mandatory asystolic observation period. Despite current ASTS recommendation of a 2-min waiting time, there is little standardization across institutions that vary between 2 and 5 min. Similarly, other publications have demonstrated the lack of standardization in the declaration of circulatory death.3 Additional guidance by the ILTS on these topics would optimize DCD liver procurement process to further reduce warm ischemic times and ultimately improve patient outcomes. Currently, 11 high-volume transplant centers perform nearly half (46.3%) of all DCD LT in the United States.4 However, recent changes to the allocation policies will result in wider sharing of DCD organs and increase distribution to lower volume centers. This will undoubtedly place greater emphasis on procedures to maintain outcomes, such as broader use of hypothermic machine perfusion and normothermic machine perfusion in LT. Machine perfusion with LT has shown promising results in the United States. One investigation discovered no difference in patient survival in ex vivo MP despite substantially longer CIT.5 MP has the potential to significantly improve DCD liver procurement and reduce discard rates. In 2019 alone, 1945 potential DCD livers were not transplanted including 306 grafts, which were discarded after recovery. The trend of increasing DCD LT in the United States has been accompanied with 30% discard rate compared with 7.1% for DBD LT.5 Furthermore, one center reported that only 47.9% of DCD liver offers resulted in a successful procurement, compared with 92.3% for DBD.6 Nasralla et al demonstrated 50% reduction in graft injury, discard, and postreperfusion injury rates in an normothermic machine perfusion clinical trial.7 A publication by the Groningen group on dual hypothermic oxygenated MP highlighted lower rates of nonanastomotic biliary strictures, postreperfusion syndrome, and early graft dysfunction compared with static cold storage in DCD LT.8 MP could remarkably impact the American LT waitlist by increasing potential DCD livers that are transplanted. We congratulate Hessheimer et al on their valuable contributions. We are pleased to see the growing support for procurement procedures such as withdrawal of life support treatment in the operating room and premortem heparin administration. Despite strong surgeon preference for both of these, our survey revealed that 26 OPO did not have specific regulations on the location of withdrawal of life support treatment and 3 OPO prohibited heparin use.2,3 We hope that the ILTS recommendations lead to updates in DCD procurement protocol and regulations to comply with the latest evidence in the literature. We hope to see more analyses of liver perfusion solutions and the various additives. We anticipate similar best practice guidance by the ASTS for normothermic and hypothermic regional perfusion in liver transplantation in the near future. Reduction in variable DCD liver recovery will be tremendously impactful in increasing the utilization of DCD livers and reducing graft discard rates.

Optimal kidney graft outcomes after simultaneous liver-kidney (SLK) transplant may be threatened by the increased cold ischemia time and hemodynamic perturbations of dual organ transplantation. Hypothermic machine perfusion (MP) of kidney allografts may mitigate these effects. We analyzed U.S. trends and renal outcomes of hypothermic non-oxygenated MP vs. static cold storage (CS) of kidney grafts from 6,689 SLK transplants performed between 2005 and 2020 using the United Network for Organ Sharing database. Outcomes included delayed graft function (DGF), primary non-function (PNF), and kidney graft survival (GS). Overall, 17.2% of kidney allografts were placed on MP. Kidney cold ischemia time was longer in the MP group (median 12.8 vs. 10.0h; p < 0.001). Nationally, MP utilization in SLK increased from <3% in 2005 to >25% by 2019. Center preference was the primary determinant of whether a graft underwent MP vs. CS (intraclass correlation coefficient 65.0%). MP reduced DGF (adjusted OR 0.74; p = 0.008), but not PNF (p = 0.637). Improved GS with MP was only observed with Kidney Donor Profile Index <20% (HR 0.71; p = 0.030). Kidney MP has increased significantly in SLK in the U.S. in a heterogeneous manner and with variable short-term benefits. Additional studies are needed to determine the ideal utilization for MP in SLK.

Introduction: Hypothermic machine perfusion (HMP) remains investigational in clinical liver transplantation despite widespread utilization in renal transplantation with improved results. Our group has reported the only clinical liver HMP series worldwide with promising results. The aim of this study was to investigate liver HMP in Extended Criteria Donor (ECD) Livers turned down by all other centers in the originating UNOS region (“orphan livers”). Methods: All included HMP livers were “orphan livers” and met at least one of the following ECD Criteria 1) Donor age>65; 2) >25% Macrosteatosis; 3) HCV+ and at least 15% macrosteatosis; 4) donor ischemic injury with AST or ALT>1,000 at time of offer. Thirty one livers were included in the study and underwent HMP for 3-7hrs using centrifugal perfusion with Vasosol® solution and were allografts for solitary, primary transplants in patients with a MELD score<35. These cases were matched to historical Cold Storage (CS) controls based on donor and recipient age, cold ischemic time, donor risk index and MELD score. Results: There were no technical or mechanical failures of HMP. Perfusate electrolytes and parameters were stable in almost all cases. Perfusate levels of AST correlated with the recipient’s peak serum AST on linear regression. There were 2 cases of Primary nonfunction in the CS group and one in the HMP group. Early allograft dysfunction (EAD) rates were 30% in CS controls vs 19% in the HMP group. Time to normalization of serum markers of liver and renal function were lower in the HMP group with serum creatinine on POD 5 being significantly lower in the HMP group. At 12 months, there were five deaths in the HMP group and 6 in the CS group (p=NS). Biliary complications were significantly lower in the HMP group compared to the CS group (4 vs 13, p=0.016) with almost twice as many ERCPs required in the CS group. Mean hospital stay was significantly shorter in the HMP group (13.65±10.9 days vs. 20.14±11.12 days in the CS group, p=0.012). HMP of orphan extended criteria donor livers provided safe and reliable preservation with significantly less biliary complications and overall length of stay in HMP patients. Further multicenter experience with HMP is necessary to further elucidate clinical benefits of HMP in Liver Transplantation.

Objective The aim of this research was to investigate the expression of KLF2 and nuclear factor- kappa B P65(NF-κB P65) in hypothermic machine perfusion and its role in liver inflammatory response after rat liver transplantation from non-heart-beating donor. Methods Twelve rats were randomly divided into two groups: HMP group(n=6) and cold storage (CS) group(n=6). With 30min of hepatic pedicle occlusion, the rats were sacrificed and liver were obtained. HMP group experienced HMP and CS group experienced CS for 3h, respectively. Using the Isolated perfused rat liver model (IPRL) to mimick the reperfusion after transplantation. During normothermic reperfusion, intrahepatic resistance (IR) was calculated, the activities of hepatic enzyme in perfusate and oxygen consumption were monitored and production of bile was evaluated. After normothermic reperfusion, livers were obtained for histological study, the expression of Kruppel-like Factor 2(KLF2) and NF-κBP65 were detected by Western Blot and the expression of TNF-α and IL-1β in liver were detected by ELISA. Results 1. After 0min, 60min, 120min of reperfusion, levels of ALT、AST、LDH in HMP group were significant lower than these in CS group (P 0.05). 2. In HMP group, hepatic sinusoids were somewhat dilated and only a very few hepatic cell edema, while CS group showed a serious liver injury including large hepatic cell edema, cytoplasmic loose, congestion and inflammation cells in the hepatic sinusoidal. 3. The expression of KLF2 in HMP group were significantly higher than CS group(P<0.05), while the expression of NF-κBP65、TNF-αand IL-1βin HMP group were significantly lower than CS group (P<0.05). Conclusion HMP could decrease liver inflammation response after liver reperfusion of non-heart-beating donor through upregulating KLF2 and inhibiting NF-κB p65 expression. Key words: Rats; Liver; Machine perfusion; Cold preservation; Kruppel like factor 2

Introduction: Liver transplantation remains the definitive treatment for end-stage liver disease but faces critical challenges including organ shortages and preservation difficulties, particularly with extended criteria donor (ECD) grafts. Hypothermic machine perfusion (HMP) represents a promising alternative to traditional static cold storage (SCS). Methods: This retrospective study analyzed outcomes from 62 liver transplant recipients between 2016 and 2025, comparing 8 grafts preserved by HMP using the Liver Assist® system and 54 grafts preserved by SCS. Parameters assessed included postoperative complications, hemodynamic stability, ischemia times, and survival outcomes. Results: HMP significantly reduced surgical (0% vs. 75.9%, p = 0.01) and biliary complications (0% vs. 34.4%, p = 0.004), improved hemodynamic stability post-reperfusion (∆MAP%: 1 vs. 21, p = 0.006), and achieved superior one-year survival rates (100% vs. 84.4%). Despite longer ischemia periods, grafts treated with HMP exhibited fewer adverse effects from ischemia-reperfusion injury. Discussion: These findings highlight the substantial benefits of HMP, particularly in improving graft quality from marginal donors and reducing postoperative morbidity. Further adoption of this technology could significantly impact liver transplantation outcomes by expanding the viable donor pool. Conclusions: The study underscores the effectiveness of hypothermic machine perfusion (HMP) as a superior preservation method compared to traditional static cold storage (SCS), HMP appears to be associated with improved short-term outcomes in liver transplantation. By substantially reducing postoperative complications and enhancing graft viability, HMP emerges as a pivotal strategy for maximizing the use of marginal donor organs. Further research and broader clinical implementation are recommended to validate these promising results and to fully harness the potential of HMP in liver transplantation.

Background. With the intent to mitigate waitlist disparities, the median model for end-stage liver disease (MELD) at transplant minus 3 policy nevertheless decreased access to liver transplant for patients with hepatocellular carcinoma (HCC). However, the adoption of machine perfusion (MP) technologies has shown promise in improving deceased donor graft yield and utilization. To understand current use for patients with HCC, we examined liver transplant patterns with MP and the characteristics of patients with HCC receiving an MP liver. Methods. Adult patients with HCC undergoing deceased donor liver transplant from September 29, 2021, to March 30, 2024, were identified using the United Network for Organ Sharing Standard Transplant Analysis and Research files. Patients were excluded if listed as status 1A or they underwent multiorgan or split liver transplant. Multivariate analysis compared patients with HCC receiving an MP liver with those receiving a static cold storage liver. Results. Of 3774 liver recipients with HCC, 593 (15.7%) underwent transplant with an MP graft. Compared with patients donation after circulatory death graft receiving a graft with static cold storage preservation, those with MP had less advanced disease (ie, Child-Pugh class C cirrhosis 22.9% versus 29.9%, P &lt; 0.01) and lower median match MELD (13 versus 17, P &lt; 0.001). Tumor characteristics were similar between groups, including alpha-fetoprotein level, maximum tumor size, and locoregional treatments. Donor factors, and not tumor burden, were most predictive of receipt of an MP liver (donation after circulatory death graft: odds ratio [OR], 14.81; macrosteatosis &gt;30%; OR, 3.85; donor age older than 60 y; OR, 2.34). A shorter waitlist time (6.5 versus 7.2 mo, P &lt; 0.01), with similar 1-y patient survival (93.6% versus 93.2%, P = 0.82) and graft survival (92.0% versus 91.6%, P = 0.84), was also noted in patients undergoing MP transplant. Conclusions. The strategic use of MP livers may improve graft utilization and access to liver transplants, helping offset the disadvantages of the MELD at transplant minus 3 policy for patients with HCC.

Background.Donation after circulatory death (DCD) is the major contributor to the growth in deceased organ donation in the United States. Normothermic regional perfusion (NRP) and ex situ machine perfusion (es-MP) have been vital for improving organ assessment and preservation in DCD donor organs. The procurement procedure and storage strategy for noncardiac donors were determined by liver transplant centers in the early era of machine perfusion in the United States. In this study, we analyzed the landscape of liver utilization from noncardiac DCD donors in the United States during the early era of machine perfusion.Methods.All adult (18 y and older) DCD donors in the United States for which the heart was not used for transplantation from October 1, 2020, to December 31, 2023, were compared using procurement technique (NRP versus super rapid recovery [SRR]) and storage strategy (ex situ machine perfusion [es-MP] versus static cold storage).Results.One hundred fifty-six livers were transplanted from 284 NRP donors (55% utilization) versus 2497 liver transplants from 9132 SRR donors (27% utilization). Es-MP was used in 19% (n = 30) of liver NRP cases versus 28% (n = 695) of liver SRR cases. Eight hundred fifty-one liver grafts (32%) were exposed to NRP, es-MP, or both.Conclusions.Given the variation in liver graft management, further research needs to be conducted on the optimal strategies for using technologies such as NRP and es-MP in liver transplantation in the United States; better data collection is necessary to support this research and additional strategies are required to increase access to machine perfusion on a national level are needed.