Donor Liver Research Articles

Japanese living donor liver transplantation criteria for hepatocellular carcinoma: nationwide cohort study.

Validating the expanded criteria for living donor liver transplantation for hepatocellular carcinoma using national data is highly significant. The aim of this study was to evaluate the validity of the new Japanese criteria for living donor liver transplantation for hepatocellular carcinoma patients and identify factors associated with a poor prognosis using the Japanese national data set. The study population comprised patients who underwent living donor liver transplantation for hepatocellular carcinoma at 37 centres in Japan between 2010 and 2018. In a nationwide survey, the overall survival and recurrence-free survival rates were evaluated based on the new Japanese criteria for applying the 5-5-500 rule when extending the indication beyond the Milan criteria. Prognostic factors within the Japanese criteria were determined using the Cox proportional hazards model. Patients within (485 patients) and beyond (31 patients) the Japanese criteria exhibited 5-year overall survival rates of 81% and 58% and 5-year recurrence-free survival rates of 77% and 48% respectively. Patients who met the Milan criteria, but not the 5-5-500 rule, had poorer outcomes. Multivariate analysis for 474 patients identified a neutrophil-to-lymphocyte ratio greater than or equal to 5 and a history of hepatectomy as independent risk factors. This nationwide survey confirms the validity of the Japanese criteria. The poor prognostic factors within the Japanese criteria include a neutrophil-to-lymphocyte ratio greater than or equal to 5 and previous hepatectomy.

Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study)

Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p= 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p= 0.26, p= 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. ClinicalTrials.gov Identifier: NCT05520320. This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.

The Centennial Allograft: Cumulative Kidney and Liver Function for More Than 100 Years

The maximum cumulative life span of kidneys and livers first in donors and then in transplant recipients has not been established. The purpose of this study was to determine if cumulative organ function for more than 90 years is possible for transplanted kidneys and livers. This study included kidney and liver transplants from living or deceased donors ≥55 years. Cumulative organ function (COF) = Organ Age at Donation [Years] + Tx Allograft Function [Years]. Univariate and multivariable methods were used to describe characteristics and outcomes. Between 1987 and 2022, a total of 81,807 kidney and 37,099 liver transplants were included in this study. Of all kidney grafts 2.7% but 16.6% of all liver grafts reached the 90-year COF mark. There were only 2 living donor kidneys that surpassed the 100-year mark versus 29 deceased liver grafts. The longest kidney function was 104 years and longest liver function 108 years. Multivariate analysis showed that optimal donor and recipient selection and management are predictors for allograft longevity. COF in organs exceeding 100 physiologic years is possible. Extended organ longevity was 5 times more common for livers than kidneys. These analyses support that age alone should not exclude older kidney and liver donors from consideration for transplantation.

Prosthetic Graft Migration in Living Donor Liver Transplantation: A Case for Conservative Management?

Abstract A 61-year-old male underwent living donor liver transplantation (LDLT) for decompensated chronic liver disease with hepatocellular carcinoma. The right lobe from the live donor was used as the graft. During implantation, the drainage of the anterior sector of the right lobe graft was through a reconstructed middle hepatic vein using a prosthetic polytetrafluoroethylene (PTFE) graft. Routine follow-up at 6 weeks showed a thrombosed PTFE graft with no clinical, radiological, or biochemical deterioration of the allograft. He was therefore managed conservatively. A routine computed tomography scan at 2 years demonstrated that the PTFE graft had eroded into the duodenum. Given the total absence of symptoms and the risk of complications associated with removing the graft, we decided against any surgical or endoscopic intervention. After a further 3 year period of follow-up, the patient continues to remain well. Enteric erosion of a prosthetic graft following LDLT can be managed without intervention, although long-term consequences are unknown.

Chylous Ascites: A Rare Complication After Donor Right Hepatectomy

Abstract Chylous ascites (CA) is a rare complication after abdominal surgeries, particularly donor hepatectomy and liver transplantation. We present a case of CA developed following donor right hepatectomy. Initially managed with a high-protein, low-fat diet and Sandostatin® (Octreotide Acetate), the patient’s condition improved but did not resolve. Subsequently, the treatment plan was modified to include clear oral fluids, total parenteral nutrition, and Sandostatin®, resulting in a significant improvement and ultimate discontinuation of CA drainage. This case sheds light on the management strategies for CA following donor hepatectomy and emphasizes the need for a multimodal approach.

An Audit of Intraoperative Frozen Section at a Tertiary Care Center

ABSTRACT Background: Frozen section (FS) is an important diagnostic tool for intraoperative decision-making. Audit of FS is an integral aspect of qualitative measure of pathology services. The aim of the study was to correlate FS diagnosis with final diagnosis and study diagnostic accuracy. Materials and Methods: The study was conducted for a period of 12 months from July 1, 2021, to June 31, 2022, at a tertiary care center. A total of 122 consecutive frozen cases were studied retrospectively. The FS and corresponding formalin-fixed paraffin-embedded tissue section with their final histopathological examination reports were studied and analyzed. The results were analyzed as concordant and discordant rates, which were compared with other similar studies. Reasons for discordance were discussed. Results: The patients were in the age range of 3 months to 87 years with a male:female ratio of 1.1:1. The turnaround time from receipt of sample to release of frozen report ranged from 10 to 40 min (average = 20 min). Indications of FS were for primary diagnosis of lesion (n = 66), resection margin assessment (n = 41), lymph node assessment (n = 12), and assessment of donor liver tissue (n = 3). Maximum number of specimens were from the surgery department, and the most commonly sampled site was oral cavity. The concordance and discordance rates were 95.90% and 4.10%, respectively. Conclusion: Intraoperative FS diagnosis aids in proper surgical decision-making and management. Periodic audit of FS and analysis of discrepancies is important to avoid mistakes in FS diagnosis.

Oxygenated versus non-oxygenated flush out during deceased donor liver procurement: The first proof-of-concept study in humans.

Liver transplantation is used for treating end-stage liver disease, fulminant hepatitis, and oncological malignancies and organ shortage is a major limiting factor worldwide. The use of grafts based on extended donor criteria have become internationally accepted. Oxygenated machine perfusion technologies are the most recent advances in organ transplantation; however, it is only applied after a period of cold ischemia. Due to its high cost, we aimed to use a novel device, OxyFlush®, based on oxygenation of the preservation solution, applied during liver procurement targeting the maintenance of ATP during static cold storage (SCS). Twenty patients were randomly assigned to the OxyFlush or control group based on a 1:1 ratio. In the OxyFlush group, the perfusion solution was oxygenated with OxyFlush® device while the control group received a non-oxygenated solution. Liver and the common bile duct (CBD) biopsies were obtained at three different time points. The first was at the beginning of the procedure, the second during organ preparation, and the third after total liver reperfusion. Biopsies were analyzed, and adenosine triphosphate (ATP) levels and histological scores of the liver parenchyma and CBD were assessed. Postoperative laboratory tests were performed. OxyFlush® was able to maintain ATP levels during SCS and improved the damage caused by the lack of oxygen in the CBD. However, OxyFlush® did not affect laboratory test results and histological findings of the parenchyma. We present a novel low-cost device that is feasible and could represent a valuable tool in organ preservation during SCS.

Early Conversion to Everolimus Within 180 Days of Living Donor Liver Transplantation.

Early conversion to Everolimus (EVR) post deceased donor liver transplant has been associated with improved renal function but increased rejection. Early EVR conversion has not been evaluated after living donor liver transplant (LDLT). A retrospective cohort study was conducted to compare the rate of rejection and renal function in patients converted to EVR early post-LDLT to patients on calcineurin inhibitors (CNIs). This was a single center retrospective cohort study of adult LDLT recipients between January 2012 and July 2019. Patients converted to EVR within 180 days of transplant were compared to patients on CNIs. The primary endpoint was biopsy proven acute rejection (BPAR) at 24 months posttransplant. Key secondary endpoints included eGFR at 24 months, change in eGFR, adverse events, and all-cause mortality. From a total of 173 patients involved in the study: 58 were included in the EVR group and 115 in the CNI group. Median conversion to EVR was 26 days post-LDLT. At 24 months, there was no difference in BPAR (22.7% EVR vs. 19.1% CNI, p = 0.63). Median eGFR at 24 months posttransplant was not significantly different (68.6 [24.8 to 112.4] mL/min EVR vs. 75.9 [35.6-116.2] mL/min CNI, p = 0.103). Change in eGFR from baseline was worse in the EVR group (-13.0 [-39.9 to 13.9] mL/min EVR vs. -5.0 [-31.2 to 21.2] mL/min CNI, p = 0.047). Median change from conversion to 24 months posttransplant (EVR group only) was -3.43mL/min/1.73 m2 (-21.0 to 9.6). Early EVR conversion was not associated with increased risk of rejection among LDLT recipients. Renal function was not impacted. EVR may be considered as an alternative after LDLT in patients intolerant of CNIs.

Liver Graft Machine Perfusion: From History Perspective to Modern Approaches in Transplant Surgery.

The shortage of donor organs remains an unresolved issue in livertransplantation worldwide. Consequently, strategies for expanding the donor pool are currently being developed. Donors meeting extended criteria undergo thorough evaluation, as livers obtained from marginal donors yield poorer outcomes in recipients, including exacerbated reperfusion injury, acute kidney injury, early graft dysfunction, and primary nonfunctioning graft. However, the implementation of machine perfusion has shown excellent potential in preserving donor livers and improving their characteristics to achieve better outcomes for recipients. In this review, we analyzed the global experience of using machine perfusion in livertransplantation through the history ofthe development ofthis method to the latest trends and possibilities for increasing the number of liver transplants.

Effectiveness of anatomic reconstruction of the middle hepatic vein in right lobe graft living donor liver transplantation using natural portal vein graft and synthetic graft

Effectiveness of anatomic reconstruction of the middle hepatic vein in right lobe graft living donor liver transplantation using natural portal vein graft and synthetic graft

Effects of Peroperative Cold Ischemia Time and Anhepatic Phase in Adult Living Donor Liver Transplant Recipients: Operation Time That is Not Affected by the Anhepatic Phase But is Prolonged by Cold Ischemia Time

ObjectiveIt was aimed to examine the overall role of cold ischemia time and anhepatic phase durations in terms of peroperative blood transfusion needs, hospital stay conditions and postoperative charges, and survival in recipients. Material and MethodsOne hundred forty-eight adult living donor liver transplant recipients (18 years and older) were included in the study. Whether the anhepatic phase and cold ischemia duration have an effect on the rates of surgery time, blood product transfusion, total hospital and intensive care unit stay, postoperative biliary complications, hepatic vein thrombosis, portal vein thrombosis, early postoperative bleeding, sepsis, and primary graft dysfunction. Was analyzed statistically. In addition, the effect of the anhepatic phase and cold ischemia time on graft survival was statistically examined by creating an average of the patient follow-up period. ResultsIt was observed that the operation time increased statistically as the cold ischemia time increased (P = .000). No statistically significant relationship was found between other findings and cold ischemia time and anhepatic phase. ConclusionProlonged surgery time due to increased cold ischemia time may be an important finding in terms of peroperative and postoperative results of the graft.

Comparative study between duct-to-duct anastomosis versus R-Y hepaticojejunostomy in pediatric living donor liver transplantation: A retrospective cohort study

Comparative study between duct-to-duct anastomosis versus R-Y hepaticojejunostomy in pediatric living donor liver transplantation: A retrospective cohort study

Comparative study for the outcome of living donor liver transplantation in patients with portal vein thrombosis in comparison to patients without portal vein thrombosi

Comparative study for the outcome of living donor liver transplantation in patients with portal vein thrombosis in comparison to patients without portal vein thrombosi

Effect of donor warm ischemia time during graft extraction in right lobe robotic donor hepatectomy on recipient outcomes—A propensity score matched analysis

One of the concerns specific to minimally invasive donor hepatectomy (MIDH) is the prolonged time required for graft extraction after completion of the donor hepatectomy (donor warm ischemia time [DWIT]). There has never been an objective evaluation of minimally invasive donor hepatectomy-DWIT on allograft function in living donor liver transplantation. We evaluated the effect of DWIT following robotic donor hepatectomy (RDH) on recipient outcomes and compared them with a matched cohort of open donor hepatectomy (ODH). Demographic, perioperative, and recipient’s postoperative outcome data for all right lobe (RL)-RDH performed between September 2019 and July 2023 were analyzed and compared with a propensity score matched cohort (1:1) of RL-ODH from the same time period. Of a total of 103 RL-RDH and 446 RL-ODH, unmatched and propensity score matched analysis (1:1) revealed a significantly longer DWIT in the RDH group as compared to the ODH group (9.33 ± 3.95 vs 2.87 ± 2.13, P < .0001). This did not translate into any difference in the rates of early allograft dysfunction (EAD), biliary complications, major morbidity, or overall 1-and 3-month survival. The receiver operating characteristic curve analysis threshold for DWIT-early allograft dysfunction was 9 minutes (area under receiver operating characteristic: 0.67, sensitivity = 80%, specificity = 53.8%). We show that prolonged DWIT within an acceptable range in RDH does not have deleterious effects on short-term recipient outcomes. Further long-term studies are required to confirm our findings, especially with regard to nonanastomotic biliary complications.

Donor Atheromatous Disease is a Risk Factor for Hepatic Artery Thrombosis After Liver Transplantation.

The increasing age of liver donors and transplant candidates, together with the growing prevalence of metabolic comorbidities, could impact the risk of vascular complications after liver transplantation. We enrolled a consecutive cohort of adult patients undergoing liver transplantation from 2012 to 2021 who had a blinded pathological assessment of atherosclerosis in the donor and recipient hepatic arteries (HA). Patients receiving partial or reduced grafts, retransplantation, or combined organ transplantation were excluded. The relationship between HA atherosclerosis and HA thrombosis after liver transplantation was evaluated using logistic regression in the whole study cohort and in a propensity score-matched subpopulation. Among 443 eligible patients, 272 had a full pathological evaluation of the donor and recipient HA and were included in the study. HA atheroma was present in 51.5% of donors and in 11.4% of recipients. HA thrombosis occurred in 16 patients (5.9%), being more likely in patients who received a donor with HA atherosclerosis than in those without (10.7%vs. 0.8%; p<0.001). Donor HA atherosclerosis was an independent risk factor of HA thrombosis (OR=17.79; p=0.008), and this finding was consistent in the propensity score-matched analysis according to age, sex, complex arterial anastomosis, and alcoholic liver disease (OR=19.29; p=0.007). Atheromatous disease in the recipient had no influence on the risk of HA thrombosis (OR=1.70; p=0.55). In conclusion, patients receiving donors with HA atherosclerosis are at increased risk for HA thrombosis after liver transplantation. The evaluation of the donor graft vasculature could guide antiplatelet therapy in the postoperative period.

Rescue of outflow block of the remnant left liver after extended right hemihepatectomy for resection of a tumor in the caudate lobe.

Outflow block of the liver is a life-threatening event after living donor liver transplantation. Herein, we rescued a patient suffering from the outflow block of the remnant left hemiliver caused by bending of the left hepatic vein (LHV) after right hemihepatectomy plus caudate lobectomy combined with resection of the middle hepatic vein (MHV). A metastatic tumor sized 6 cm in the caudate lobe of the liver involving the root of the MHV was found in a 50's year old patient after resection of a right breast cancer eight years ago. Right hemihepatectomy and caudate lobectomy combined with resection of the MHV was performed using a two-stage hepatectomy (partial TIPE ALPPS). On day 1, the total bilirubin value increased to 4.5 mg/dL, and a dynamic computed tomography (CT) scan showed the bent LHV. On the diagnosis of outflow block of the left liver, a self-expandable metallic stent was placed in the LHV using an interventional approach, and the pressure in the LHV decreased from 27 cmH2O to 12 cmH2O. The bilirubin value decreased to 1.2 mg/dL on day 3. Outflow block of the LHV can happen after extended right hemihepatectomy with resection of the MHV. Early diagnosis and interventional stenting treatment can rescue the patient from congestive liver failure.

Intracavitary Applications for CEUS in PTCD.

Intracavitary contrast-enhanced ultrasound is widely accepted as a highly informative, safe, and easily reproducible technique for the diagnosis, treatment, and follow-up of different pathologies of the biliary tree. This review article describes the diverse applications for CEUS in intracavitary biliary scenarios, supported by a literature review of the utilization of the method in indications like biliary obstruction by various etiologies, including postoperative strictures, evaluation of the biliary tree of liver donors, and evaluation of the localization of a drainage catheter. We also provide pictorial examples of the authors' personal experience with the use of intracavitary CEUS in cases of PTCD as a palliative intervention. Intracavitary CEUS brings all the positive features of US together with the virtues of contrast-enhanced imaging, providing comparable accuracy to the standard techniques for diagnosing biliary tree diseases.

Polyethylene glycol and caspase inhibitor emricasan alleviate cold injury in primary rat hepatocytes

Current methods of storing explanted donor livers at 4 °C in University of Wisconsin (UW) solution result in loss of graft function and ultimately lead to less-than-ideal outcomes post transplantation. Our lab has previously shown that supplementing UW solution with 35-kilodalton polyethylene glycol (PEG) has membrane stabilizing effects for cold stored primary rat hepatocytes in suspension. Expanding on past studies, we here investigate if PEG has the same beneficial effects in an adherent primary rat hepatocyte cold storage model. In addition, we investigated the extent of cold-induced apoptosis through treating cold-stored hepatocytes with pan caspase inhibitor emricasan. In parallel to storage at the current cold storage standard of 4 °C, we investigated the effects of lowering the storage temperature to −4 °C, at which the storage solution remains ice-free due to the supercooling phenomenon. We show the addition of 5 % PEG to the storage medium significantly reduced the release of lactate dehydrogenase (LDH) in plated rat hepatocytes and a combinatorial treatment with emricasan maintains hepatocyte viability and morphology following recovery from cold storage. These results show that cold-stored hepatocytes undergo multiple mechanisms of cold-induced injury and that PEG and emricasan treatment in combination with supercooling may improve cell and organ preservation.

The Risk of Microbial Transmission in Recipients of Donor Livers That Underwent Hypothermic or Normothermic Machine Perfusion.

Ex situ machine perfusion is increasingly used to preserve and assess donor livers before transplantation. Compared with traditional static cold storage (SCS), machine perfusion exposes livers to an additional risk of microbial contamination. However, information on the risk of microbial transmission during machine perfusion is lacking. All livers that underwent either hypothermic oxygenated machine perfusion (HOPE) or normothermic machine perfusion (NMP) in our center between September 2021 and September 2023, and during which samples were taken from SCS fluid and/or machine perfusion solution for microbiological examination, were included in this retrospective, observational clinical study. Microbial transmission was examined from SCS fluid to machine perfusion solution fluid and, subsequently, to recipients of these livers. A total of 90 cases of liver machine perfusion were included: 59 HOPE and 31 NMP. SCS preservation fluid cultures before HOPE or NMP were positive for at least 1 microorganism in 52% of the cases. After HOPE, there were no cases of positive machine perfusion fluid or evidence of microbial transmission to the recipients. After NMP, in 1 (3%) patient Escherichia coli was grown from abdominal drain fluid, the same bacterial strain that was also grown from the SCS preservation fluid before NMP. This E coli was resistant to the antibiotics that are routinely added to the NMP perfusion fluid. The risk of microbial transmission after machine perfusion is very low but not absent. We recommend routine sampling of machine perfusion fluid at the end of the procedure for microbiological analysis.

Randomized Controlled Trial of Enhanced Recovery After Surgery Protocols in Live Kidney Donors: ERASKT Study.

Enhanced recovery after surgery (ERAS) pathways represent a comprehensive approach to optimizing perioperative management and reducing hospital stay and cost. In living donor kidney transplantation, key impediments to postoperative discharge include pain, and opioid associated complications such as nausea, vomiting, and the return of gastrointestinal function. In this randomized controlled trial, living kidney transplantation donors were assigned to either the ERAS or control group. The ERAS group patients received 15 preoperative, 17 intraoperative, 19 postoperative element intervention. The control group received standard care. The ERAS group received a multimodal opioid sparing pain management including an intraoperative transverse abdominis plane block. Our primary outcome measure was postoperative opioid consumption. The secondary outcome measures were postoperative pain scores, first oral intake, and hospital length of stay. There were no significant differences in demographics between the 2 groups. The ERAS group had a statistically significant reduction in total postoperative opioid consumption calculated in intravenous morphine equivalents (24.2 ± 20.2 versus 71 ± 39.5 mg, P < 0.01). Postoperative pain scores were significantly lower (P < 0.001) from 1 h postoperatively to 48 h. Surgical time was 45 min shorter (P = 0.037). Intraoperative PlasmaLyte administration was lower (PlasmaLyte: 1444 ± 907 versus 2168 ± 1347 mL, P = 0.049). Time to tolerating regular diet was shorter by 2 h (P < 0.008), and length of hospital stay was decreased by 10.1 h. The ERAS group experienced superior postoperative analgesia and a shorter length of hospital stay compared with controls.