Comparable graft survival is achievable with the usage of donation after circulatory death liver grafts from donors at or above 70 years of age: A long-term UK national analysis

The aim of the study was to assess the UK donation after circulatory death (DCD) liver transplant experience from donors ≥70 years. Nationwide UK DCD retrospective analysis was conducted between 2001 and 2015 (n = 1163). Recipients were divided into group 1 vs. group 2 (donors 70≥ vs. <70 years, respectively). group 1 (n = 69, 5.9%) recipients were older (median 59 vs. 55 years, p = .001) and had longer waitlist time (128 vs. 84 days; p = .039). 94.2% of group 1 clustered in London and Birmingham, where the two busiest centers are located. group 1 allografts had higher UKDRI and UK DCD Risk Scores but similar WIT and CIT and were more likely to have been imported. Both groups had similar 1-, 3-, and 5-year graft survival (group 1, 90%, 81.4%, and 74% vs. group 2, 88.6%, 81.4%, and 78.6%, respectively; p = .54). Both groups had similar ICU stay length (p = .22), 3-month hepatic artery thrombosis rates (4.4% vs 4.0%; p = .9), and 12-month readmission rates for all biliary complications (20.3% vs 25.7%; p = .32). This study demonstrates that acceptable outcomes are achievable using older grafts in a highly selected cohort at experienced centers. Advanced age should not be an absolute contraindication to utilizing a DCD graft from donors aged ≥70 years.     

Immediate administration of antiviral therapy after transplantation of hepatitis C‐infected livers into uninfected recipients: Implications for therapeutic planning

The practice of transplanting hepatitis C (HCV)‐infected livers into HCV‐uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct‐acting antivirals (DAAs) provide an opportunity to treat donor‐derived HCV‐infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV‐positive donor organs. We report the results of a trial in which 14 HCV‐negative patients underwent successful liver transplantation from HCV‐positive donors. Nine patients received viremic (nucleic acid testing [NAT]‐positive) livers and started a 12‐week course of oral glecaprevir‐pibrentasvir within 5 days of transplant. Five patients received livers from HCV antibody‐positive nonviremic donors and were followed using a reactive approach. Survival in NAT‐positive recipients is 100% at a median follow‐up of 46 weeks. An immediate treatment approach for HCV NAT‐positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the posttransplant course could enable need‐based allocation of HCV‐positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection.     

Liver transplantation performed in a SARS-CoV-2 positive hospitalized recipient using a SARS-CoV-2 infected donor

The coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 currently affected more than 108 million people worldwide with a fatality rate of 2.2%. Herein, we report the first case of liver transplantation (LT) performed with a liver procured from a SARS-CoV-2 positive donor. The recipient was a 35-year-old SARS-CoV-2 positive female patient affected by severe end-stage HBV-HDV-related liver disease (model of end-stage liver disease = 32) who had neutralizing SARS-CoV-2 antibodies (titers 1:320) at time of LT. The LT was successful, and the graft is functioning two months after surgery. The recipient cleared the SARS-CoV-2 infection 1 month after LT. The current case shows that the prompt use of SARS-CoV-2 infected liver donors offers an invaluable life-saving opportunity for SARS-CoV-2 positive wait-listed patients who developed neutralizing SARS-CoV-2 antibodies.     

Pretransplant sequential hypo‐ and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin‐based oxygen carrier perfusion solution

Ex situ dual hypothermic oxygenated machine perfusion (DHOPE) and normothermic machine perfusion (NMP) of donor livers may have a complementary effect when applied sequentially. While DHOPE resuscitates the mitochondria and increases hepatic adenosine triphosphate (ATP) content, NMP enables hepatobiliary viability assessment prior to transplantation. In contrast to DHOPE, NMP requires a perfusion solution with an oxygen carrier, for which red blood cells (RBC) have been used in most series. RBC, however, have limitations and cannot be used cold. We, therefore, established a protocol of sequential DHOPE, controlled oxygenated rewarming (COR), and NMP using a new hemoglobin‐based oxygen carrier (HBOC)‐based perfusion fluid (DHOPE‐COR‐NMP trial, NTR5972). Seven livers from donation after circulatory death (DCD) donors, which were initially declined for transplantation nationwide, underwent DHOPE‐COR‐NMP. Livers were considered transplantable if perfusate pH and lactate normalized, bile production was ≥10 mL and biliary pH > 7.45 within 150 minutes of NMP. Based on these criteria five livers were transplanted. The primary endpoint, 3‐month graft survival, was a 100%. In conclusion, sequential DHOPE‐COR‐NMP using an HBOC‐based perfusion fluid offers a novel method of liver machine perfusion for combined resuscitation and viability testing of suboptimal livers prior to transplantation.     

Ex situ machine perfusion as a tool to recondition steatotic donor livers: Troublesome features of fatty livers and the role of defatting therapies. A systematic review.

Long‐standing research has shown that increased lipid content in donor livers is associated with inferior graft outcomes posttransplant. The global epidemic that is obesity has increased the prevalence of steatosis in organ donors, to the extent that it has become one of the main reasons for declining livers for transplantation. Consequently, it is one of the major culprits behind the discrepancy between the number of donor livers offered for transplantation and those that go on to be transplanted. Steatotic livers are characterized by poor microcirculation, depleted energy stores because of an impaired capacity for mitochondrial recovery, and a propensity for an exaggerated inflammatory response following reperfusion injury culminating in poorer graft function postoperatively. Ex situ machine perfusion, currently a novel method in graft preservation, is showing great promise in providing a tool for the recovery and reconditioning of marginal livers. Hence, reconditioning these steatotic livers using machine perfusion has the potential to increase the number of liver transplants performed. In this review, we consider the problematic issues associated with fatty livers in the realm of transplantation and discuss pharmacological and nonpharmacological options that are being developed to enhance recovery of these organs using machine perfusion and defatting strategies.     

Trends in deceased donor liver enzymes prior to transplant: The impact on graft selection and outcomes

We sought to characterize the trend in alanine aminotransferase elevations prior to transplant and the impact on the pattern of enzyme elevations on organ utilization and graft function. We performed a retrospective cohort study of UNOS data on all deceased donors between 2007 and 2016. Serum alanine aminotransferase (ALT) was categorized into six study groups with peak ALT < 499, 500‐749, 750‐999, 1000‐1999, 2000‐2999, and >3000 IU/L. The change from peak ALT to terminal ALT prior to transplant was categorized as no change/increasing at time transplant, 0.1‐9.9%, 10‐24.9%, 25‐49.9%, 50‐74.9% and >75% change. In multivariable models evaluating liver utilization, the interaction between peak ALT and percent change in ALT was most pronounced at the highest peak ALT levels, where liver utilization varied markedly as a function of percentage drop from peak to terminal ALT. There was no increased risk of graft failure based on peak ALT. Markers of ischemic liver injury and recovery are significantly associated with liver utilization, yet among transplanted livers they were not associated with graft outcomes and may represent an area to expand the donor pool.     

Propensity score–based comparison of the graft failure risk between kidney transplant recipients of standard and expanded criteria donor grafts: Toward increasing the pool of marginal donors

From a prospective and multicentric French cohort, we proposed an external validation study for the expanded criteria donor (ECD), based on 4833 kidney recipients transplanted for the first time between 2000 and 2014. We estimated the subject‐specific effect from a multivariable Cox model. We confirmed a 1.75‐fold (95% confidence interval [CI] 1.53‐2.00, P < .0001) increase in graft failure risk if a given patient received an ECD graft compared to a graft from a donor with standard criteria (standard criteria donor [SCD]). Complementarily, we estimated the population‐average effect using propensity scores. We estimated a 1.34‐fold (95% CI 1.09‐1.64, P = .0049) increase in graft failure risk among ECD patients receiving an ECD graft compared to receiving a SCD graft. With a 10‐year follow‐up, it corresponded to a decrease of 8 months of the mean time to graft failure due to ECD transplantation (95% CI 2‐14 months). The population‐average relative risk due to ECD transplantation and the corresponding absolute effect seem finally not so high. Regarding the increase of quality of life in transplantation, our study constitutes an argument to extend the definition of marginality by considering more grafts at high risk and thereby enlarging the pool of kidney grafts.     

Controlled donation after circulatory death up to 80 years for liver transplantation: Pushing the limit again

Our main objective was to compare liver transplant (LT) results between donation after circulatory death (DCD) and donation after brainstem death (DBD) in our hospital and to analyze, within the DCD group, the influence of age on the results obtained with DCD donors aged >70 years and up to 80 years. All DCD‐LTs performed were analyzed prospectively. The results of the DCD group were compared with those of a control group who received a DBD‐LT immediately after each DCD‐LT. Later, the results obtained within the DCD group were analyzed according to the age of the donors, considering 2 subgroups with a cut‐off point at 70 years. Survival results for LT with DCD and super rapid recovery were not inferior to those obtained in a similar group of patients transplanted with DBD livers. However, the cost of DCD was a higher rate of biliary complications, including ischemic cholangiopathy. Donor age was not a negative factor.     

Lung transplantation from swimming pool drowning victims: A case series

The use of donor lungs from victims of drowning remains a rare occurrence, given concerns over lung parenchymal injury and microbial contamination secondary to aspiration. Given this infrequency, there is a relative paucity of literature surrounding the use of organs from drowned donors, with the few that exist on this subject focusing primarily on cases of drowning in naturally occurring bodies of water (i.e., drowning at sea). Little is known regarding the outcomes of utilizing donor lungs from victims of drowning in artificial bodies of water (i.e., swimming pools). Here, we describe three cases of bilateral lung transplantation from donors who drowned in swimming pools, with good short- and long-term outcomes. These cases lend further evidence to the feasibility of using such organs that have traditionally been viewed with much trepidation. With continually growing demand for donor organs, the use of drowned donor lungs may serve as a means to expand the donor pool and lessen the burden of waitlist mortality.     

Organ procurement center allows for daytime liver transplantation with less resource utilization: May address burnout,pipeline, and safety for field of transplantation

Abdominal organ transplantation faces several challenges: burnout, limited pipeline of future surgeons, changes in liver allocation potentially impacting organ procurement travel, and travel safety. The organ procurement center (OPC) model may be one way to mitigate these issues. Liver transplants from 2009 to 2016 were reviewed. There were 755 liver transplants performed with 525 OPC and 230 in‐hospital procurements. The majority of transplants (87.4%) were started during daytime hours (5 am ‐7 pm ). Transplants with any portion occurring after‐hours were more likely to have procurements in‐hospital (P < .001). Daytime cases (n = 400) had more OPC procured livers and hepatitis C recipients and were less likely to have a donation after circulatory death donor (all P < .05). In adjusted analyses, daytime cases were independently associated with extubation in the operating room and less postoperative transfusion. There were no significant differences in short‐ or long‐term postoperative outcomes. For exported livers, 54.3% were procured by a local team, saving 137 flights (151 559 miles). The OPC resulted in optimally timed liver transplants and decreased resource utilization with no negative impact on patient outcomes. It allows for ease in exporting organs procured by local surgeons, and potentially addresses provider burnout, the transplant surgery pipeline, and surgeon travel.     

Pediatric living donor liver transplantation with large‐for‐size left lateral segment grafts

Usage of “large‐for‐size” left lateral segment (LLS) liver grafts in children with high graft to recipient weight ratio (GRWR) is controversial due to concerns about increased recipient complications. During the study period, 77 pediatric living donor liver transplantations (LDLTs) with LLS grafts were performed. We compared recipients with GRWR ≥2.5% (GR‐High = 50) vs GRWR <2.5% (GR‐Low = 27). Median age was higher in the GR‐Low group (40 vs 8 months, P> .0001). Graft (GR‐High: 98%, 98%, 98% vs GR‐Low: 96%, 93%, 93%) and patient (GR‐High: 98%, 98%, 98% vs GR‐Low: 100%, 96%, 96%) survival at 1, 3, and 5 years was similar between groups (P = NS). Overall complications were also similar (34% vs 30%; P = .8). Hepatic artery and portal vein thrombosis following transplantation was not different (P = NS). Delayed abdominal fascia closure was more common in GR‐High patients (17 vs 1; P = .002). Subgroup analysis comparing recipients with GRWR ≥4% (GR‐XL = 20) to GRWR <2.5% (GRWR‐Low = 27) revealed that delayed abdominal fascia closure was more common in the GR‐XL group, but postoperative complications and graft and patient survival were similar. We conclude that pediatric LDLT with large‐for‐size LLS grafts is associated with excellent clinical outcomes. There is an increased need for delayed abdominal closure with no compromise of long‐term outcomes. The use of high GRWR expands the donor pool and improves timely access to the benefits of transplantation without extra risks.     

Temporal trends in utilization and outcomes of steatotic donor livers in the United States

Steatotic donor livers (SDLs) (macrosteatosis ≥30%) represent a possible donor pool expansion, but are frequently discarded due to a historical association with mortality and graft loss. However, changes in recipient/donor demographics, allocation policy, and clinical protocols might have altered utilization and outcomes of SDLs. We used Scientific Registry of Transplant Recipients data from 2005 to 2017 and adjusted multilevel regression to quantify temporal trends in discard rates (logistic) and posttransplant outcomes (Cox) of SDLs, accounting for Organ Procurement Organization–level variation. Of 4346 recovered SDLs, 58.0% were discarded in 2005, versus only 43.1% in 2017 (P < .001). SDLs were always substantially more likely discarded versus non‐SDLs, although this difference decreased over time (adjusted odds ratio in 2005‐2007:_13.1515.28_17.74; 2008‐2011:_11.7713.41_15.29; 2012‐2014:_9.8711.37_13.10; 2015‐2017:_7.798.89_10.15, P < .001 for all). Conversely, posttransplant outcomes of recipients of SDLs improved over time: recipients of SDLs from 2012 to 2017 had 46% lower risk of mortality (adjusted hazard ratio [aHR]: _0.430.54_0.68, P < .001) and 47% lower risk of graft loss (aHR: _0.420.53_0.67, P < .001) compared to 2005 to 2011. In fact, in 2012 to 2017, recipients of SDLs had equivalent mortality (aHR: _0.901.04_1.21, P = .6) and graft loss (aHR: _0.901.04_1.20, P = .6) to recipients of non‐SDLs. Increasing utilization of SDLs might be a reasonable strategy to expand the donor pool.     

Single lung transplantation from a donor 8 months after double lung transplantation

Scarcity of donors leads transplant surgeons to consider extended‐criteria lungs and occasionally to accept the unlikely. Here we report a case of successful single lung transplantation from a donor 8 months after double lung transplantation.