Donor Liver Research Articles

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.

The long-term follow-up of the living liver donors.

Living donor liver transplantation (LDLT) has been proposed in many countries to reduce organ shortage. While the early postoperative outcomes have been well investigated, little is known about the long-term follow-up of the living donors. We, therefore, designed a systematic review of the literature to explore long-term complications and quality of life among living donors. We searched MEDLINE and EMBASE registries for studies published since 2013 that specifically addressed long-term follow-up following living-donor liver donation, concerning both physical and psychological aspects. Publications with a follow-up shorter than 1 year or that did not clearly state the timing of outcomes were excluded. A total of 2505 papers were initially identified. After a thorough selection, 17 articles were identified as meeting the eligibility criteria. The selected articles were mostly from North America and Eastern countries. Follow-up periods ranged from 1 to 11.5 years. The most common complications were incision site discomfort (13.2-38.8%) and psychiatric disorders (1-22%). Biliary strictures occurred in 1-14% of cases. Minimally invasive donor hepatectomy could improve quality of life, but long-term data are limited. About 30 years after the first reported LDLT, little has been published about the long-term follow-up of the living donors. Different factors may contribute to this gap, including the fact that, as healthy individuals, living donors are frequently lost during mid-term follow-up. Although the reported studies seem to confirm long-term donor safety, further research is needed to address the real-life long-term impact of this procedure.

Effects of Hepatic Artery Type And Number on Bile Complications in Right Lobe Living Donor Liver Transplant Recipients: Single Center Experience Without Hepatic Artery Thrombosis

Purpose: Hepatic artery provides blood supply to the biliary tract of the graft, one of the causes of the biliary complications that may occur in the post-transplant period may be the problems of the recipient's hepatic artery. We examined the effect of post-transplant biliary complications according to the type and number of recipient hepatic artery. Materials and Methods: One hundred eighty five patients older than 18 years of age who underwent right lobe LDLT for end-stage liver cirrhosis were included in the study. The recipient's right hepatic artery (RHA), left hepatic artery (LHA), propria hepatic artery (PHA) and common hepatic artery (CHA), which were anastomosed to the graft artery and double hepatic artery anastomoses formed of the right and left hepatic arteries, were examined. Biliary complications were analyzed statistically in terms of single or double artery anastomosis and anastomoses with the right or the other hepatic arteries. Results: There was no statistically significant difference between single and dual artery anastomoses in terms of bile duct stricture or leakage (p=0.767). No statistically significant difference was observed between RHA, LHA, PHA, CHA, and between single and dual arteries in the evaluation of artery selection between those with and without biliary tract complications (p=0.445) Conclusion: Hepatic artery type selection and number of the recipient does not change the biliary tract complication.

Single-center experience of intraoperative ligation of the splenic artery for prevention of splenic artery steal syndrome in patients after living donor liver transplant

Background. Living donor liver transplant is an effective method of treatment in patients with different types of endstage liver diseases. Unfortunately, patients undergoing such a complex treatment sometimes develop various vascular complications. Splenic artery steal syndrome has emerged as a cause of graft ischemia in living donor liver transplant recipients and may lead to high liver enzyme levels, cholestasis, hepatic artery thrombosis, and even a graft loss in some severe cases.Objective. Evaluation of the first results in the experience of our center with a routine intraoperative ligation of the splenic artery during the procedure of right lobe living donor liver transplantation in adult recipients for the prevention of the steal syndrome development in the postoperative period.Material and methods. Living donor liver transplant recipients with known hepatic arterial flow impairment were retrospectively studied. Patients were allocated into groups with regard whether the splenic artery had been ligated or not during the transplant procedure. Arterial complications were reviewed in both groups.Results. None of 30 patients with ligated splenic artery developed splenic artery steal syndrome after living donor liver transplant. splenic artery steal syndrome occurred in 60% patients with non-ligated splenic artery. Surgical technique of performing arterial anastomosis was not related to the splenic artery steal syndrome development (p&lt;0.01 There was no local ischemic necrosis noted in the spleen in patients with the ligated splenic artery.Conclusion. Based on the analysis of our own experience and literature data, the splenic artery ligation appears to be an effective and safe method for preventing a splenic artery steal syndrome in patients following right lobe liver transplantation, with a minimal risk of ischemic complications for the spleen. However, further studies with larger sample sizes are needed to obtain more reliable results. Ultrasound examination and endovascular intervention are the primary tools for an early detection of abnormalities and rapid restoration of arterial blood flow in the hepatic artery of the graft.

Implementation of a living donor liver transplantation program in the Republic of Uzbekistan: a report of the first 40 cases.

Living donor liver transplantation (LDLT) is an effective treatment for patients with end-stage liver disease. This study was performed to evaluate the outcomes of the initial series of LDLT procedures performed in the Republic of Uzbekistan and to demonstrate that liver transplantation is viable under the conditions in this country. Between October 2021 and December 2023, we performed 40 LDLTs. We evaluated both immediate and long-term outcomes. Thrombosis of the hepatic artery developed in one case (2.5%). Arterial anastomotic stenoses were diagnosed in three cases (7.5%) and were successfully treated with endovascular balloon vasodilation. Splenic artery steal syndrome arose in three patients (7.5%) and was managed with endovascular embolization of the splenic artery. One patient (2.5%) developed portal vein thrombosis. Portal vein stenosis occurred in two patients (5%) at 10 months posttransplantation and was addressed with endovascular balloon angioplasty, yielding good clinical outcomes. Biliary complications were observed in 45% of the cases, with bile leakages accounting for 89% of these issues and strictures of the biliary anastomoses for 11%. The in-hospital mortality rate was 12.5%. Our research findings and analysis of complications align with the international literature, and the results are deemed acceptable during this implementation phase of the liver transplantation program. Accordingly, liver transplantation is feasible in the Republic of Uzbekistan; however, improvements in surgical and therapeutic methods are necessary to minimize the development of both early and late postoperative complications.

A case of severe anaphylactic reaction after administration of diagnostic-dose ferumoxytol in a pediatric patient

We describe a case of anaphylaxis during administration of intravenous (IV) ferumoxytol as a magnetic resonance imaging (MRI) contrast agent in a 4-year-old patient with complicated past medical history including YARS genetic mutation with resultant liver failure and deceased donor liver transplantation, stage IV chronic kidney disease (CKD), and hypertension. The patient was noted to have labored breathing 4 min after initiation of ferumoxytol infusion and was subsequently rapidly intubated and returned to the intensive care unit (ICU) for monitoring. Anaphylactic reactions to therapeutic doses of ferumoxytol led to issuance of a black box warning by the FDA in 2015. Adverse reactions to lower-dose ferumoxytol used in diagnostic imaging, however, are rare and there has been a paucity of documented anaphylactic reactions in the literature.

Viability assessment and transplantation of extended criteria donor liver grafts using normothermic machine perfusion

BackgroundThe scarcity of available liver grafts necessitates the use of organs from extended criteria donors, a practice associated with an increased risk of graft failure. A notable percentage of deceased donor liver allografts are rejected due to subjective criteria. Normothermic machine perfusion holds promise for introducing objective parameters into this decision-making process. The aim of this study was to compare the outcomes of standard criteria and extended criteria donor allografts after liver transplantation, following viability assessment, using normothermic machine perfusion. MethodsLiver allografts preserved by normothermic machine perfusion before liver transplantation at the University Hospital of Münster were retrospectively analyzed. Organs were stratified according to the Eurotransplant Donor Risk Index. In total, 101 liver grafts were included in this study and divided into 2 groups: (1) standard criteria donors with a Donor Risk Index <1.8 (DRI-low) and (2) extended criteria donors with a Donor Risk Index ≥1.8 (DRI-high). ResultsAn increased risk profile of donor livers, as assessed by the Eurotransplant Donor Risk Index, did not correlate with patient or graft survival. High-risk liver grafts were effectively transplanted into recipients with different risk levels after viability assessment by normothermic machine perfusion. However, the recipients’ model for end-stage liver disease scores showed a significant association with both overall patient and graft survival. ConclusionThe use of normothermic machine perfusion for viability assessment allows safe transplantation of high-risk donor livers and effectively addresses the disparity between donor liver availability and transplantation demand.

The Impact of Donor Body Mass Index on Safety and Outcomes in Living Donor Liver Transplantation: An Analysis of the National United States Database.

The prevalence of obesity is rising in the general population. Donor obesity (body mass index ≥30 kg/m2) may potentially reduce the donor pool and impact outcomes in living donor liver transplantation (LDLT). We utilized the national transplant database to investigate the impact of donor obesity on donor and recipient outcomes. This was a retrospective cohort study of all LDLTs performed in the United States between January 2010 and June 2023. Outcomes of interest were analyzed by univariable and multivariable logistic regression. Patient and graft survival was evaluated using Kaplan-Meier and Cox proportional analysis. Six hundred seventy-four donors with obesity and 3498 donors without obesity were analyzed. Donors with obesity had higher rates of readmission within 1 y of donation (15.9% versus 11.6%; P = 0.003). The risk of readmission was significantly different between 6 wk and 6 mo of donation (8.8% versus 5.9%; P = 0.036). Donor body mass index (odds ratio [OR], 1.460; 95% confidence interval [CI], 1.129-1.999; P = 0.004) and preoperative alkaline phosphatase levels (OR, 1.005; 95% CI, 1.000-1.011; P = 0.038) were independent predictors of donor readmission. High LDLT center volume was associated with reduced odds of donor readmission (OR, 0.509; 95% CI, 0.373-0.694; P < 0.001). Graft and recipient survival was comparable. Selection of living donors with obesity may be a potential avenue to increase the available donor pool without compromising recipient outcomes; however, they are at an increased risk for readmission between 6 wk and 6 mo of donation. The reason for readmission requires further study.

Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time?

Liver transplantation (LT) provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma. Despite the increasing number of liver transplants performed each year, the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality. Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates. Nevertheless, further strategies can be implemented to increase the pool of potential donors in deceased donor LT, such as reducing the rate of organ discards. Utilizing hepatitis C virus (HCV) seropositive liver grafts is one of the expanded donor organ criteria. A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients. Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation. The American Society of Transplantation advises against performing transplants from HCV-infected liver donors (D+) into HCV-negative recipient (R-) unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants. Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is important. National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.

Defatting of donor transplant livers during normothermic perfusion—a randomised clinical trial: study protocol for the DeFat study

BackgroundLiver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes.MethodsIn the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months).DiscussionThis study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths.Trial registrationISRCTN ISRCTN14957538. Registered in October 2022.