Tauroursodeoxycholic acid and 4-phenyl butyric acid alleviate endoplasmic reticulum stress and improve prognosis of donation after cardiac death liver transplantation in rats

BACKGROUND： Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia- reperfusion injury. Endoplasmic reticulum （ER） stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death （DCD） liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid （TUDCA） and 4-phenyl butyric acid （PBA）, on the prognosis of recipient of DCD liver transplantation remains unclear. METHODS： Male Sprague-Dawley rats （8-10 weeks） were randomly divided into control group： liver grafts without warm ischemia were implanted; DCD group： warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups： based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days.RESULTS： Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation （P〈0.01, 0.01 and 0.05, respectively） and oxidative indices （P〈0.01 for both malondialdehyde and 8-hydroxy deoxyguanosine）, more severe liver damage （P〈0.01） and up-regulated ER stress signal expressions （P〈0.01 for GRP78, phos-eIF2al, CHOP, ATF-4, ATF-6, PERK, XBP-1 and pro-caspase-12）. All recipients died within 3 days after liver transplantation. Administration of TUDCA or PBA significantly decreased aminotransferase levels （P〈0.05）, increased superoxide dismutase activities （P〈0.01）, alleviated liver damage （P〈0.01）, down-regulated ER stress signal expressions （P〈0.01） and improved postoperative survivals （P〈0.01）. CONCLUSIONS： ER stress was involved with DCD liver trans- plantation in rats. Preoperative intraperitoneally injection of TUDCA or PBA protected ER stress and improved prognosis.

Risk scores for allograft failure: Are they still useful in liver recipients from donation after circulatory death?

BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise criteria to identify this complication in order to guide therapeutic strategies.AIM To validate different graft and recipient survival scores in patients undergoing liver transplantation(LT)with DCD grafts.METHODS A retrospective and observational unicentric study was conducted on 65 LT patients with grafts obtained from controlled DCD donors from November 2013 to November 2022.The United Kingdom(UK)risk score,early allograft dysfunction(EAD)Olthoff score,and model for early allograft function(MEAF)score were used to evaluate the risk of graft and recipient survival post-transplant.For survival analysis purposes,we used the Kaplan-Meier method,and the differences between subgroups were compared using the log-rank(Mantel-Cox)test.RESULTS Sixty-five patients were included in the study.The UK risk score did not demonstrate predictive capacity for recipient or graft survival.However,in donors aged over 70 years old(18.4%),it significantly predicted graft survival(P<0.05).According to Kaplan-Meier survival curves,graft survival rates at 6 months,2 years,and 5 years in the futility group dramatically decreased to 50%compared to the other groups(log-rank 8.806,P<0.05).The EAD Olthoff and MEAF scores did not demonstrate predictive capacity for recipient or graft survival.Based on Kaplan-Meier survival curves,patients with a MEAF score≥7 had a lower graft survival rate at 6 months,2 years,and 5 years compared to patients with a lower MEAF score(log-rank 4.667,P<0.05).CONCLUSION In our series,both UK DCD risk score and MEAF score showed predictive capability for graft survival.

Developing a donation after cardiac death risk index for adult and pediatric liver transplantation

AIM To identify objective predictive factors for donor after cardiac death(DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index(DCD-RI) to help in prospective decision making on organ use.METHODS The model included objective data from a single institute DCD database(2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated.RESULTS DCD graft survival predictors were primary indication for transplant(P = 0.066), retransplantation(P = 0.176), MELD > 25(P = 0.05), cold ischemia > 10 h(P = 0.292) and donor hepatectomy time > 60 min(P = 0.028).According to the calculated DCD-RI score three risk classes could be defined of low(DCD-RI < 1), standard(DCD-RI 2-4) and high risk(DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively.CONCLUSION The DCD-RI score independently predicted graft loss(P < 0.001) and the DCD-RI class predicted graft survival(P < 0.001).

Warm ischemia time and elevated serum uric acid are associated with metabolic syndrome after liver transplantation with donation after cardiac death

AIM To describe the prevalence of posttransplant metabolic syndrome(PTMS) after donation after cardiac death(DCD) liver transplantation(LT) and the pre-and postoperative risk factors.METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre-and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-Ⅲ criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147(13.6%). Recipient's body mass index(P = 0.024), warm ischemia time(WIT)(P = 0.045), and posttransplant hyperuricemia(P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients(P < 0.001). After the 1 s t mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.

Older liver grafts from donation after circulatory death are associated with impaired survival and higher incidence of biliary non-anastomotic structure

Background:Grafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past.But it has seemed to remain controversial in the last decade,as a result of modified clinical protocols,selected recipients,and advanced technology of organ perfusion and preservation.The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death(DCD).Methods:A total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups:using graft from older donor(aged≥65 years,n=87)and younger donor(age<65 years,n=857).Propensity score matching(PSM)was applied to eliminate selection bias.Results:A progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68%to 15.44%during the study period.The well-balanced older donor(n=79)and younger donor(n=79)were 1:1 matched.There were significantly more episodes of biliary nonanastomotic stricture(NAS)in the older donor group than the younger donor group[15/79(19.0%)vs.6/79(7.6%);P=0.017].The difference did not reach statistical significance regarding early allograft dysfunction(EAD)and primary non-function(PNF).Older livers had a trend toward inferior 1-,2-,3-year graft and overall survival compared with younger livers,but these differences were not statistically significant(63.1%,57.6%,57.6%vs.76.9%,70.2%,67.7%,P=0.112;64.4%,58.6%,58.6%vs.76.9%,72.2%,72.2%,P=0.064).The only risk factor for poor survival was ABO incompatible transplant(P=0.008)in the older donor group.In the subgroup of ABO incompatible cases,it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group[6/8(75.0%)vs.3/14(21.4%);P=0.014].Conclusions:Transplants with grafts from older donors(aged≥65 years)after circulatory death are more frequently associated with inferior outcome compared to those from younger donors.Older grafts from DCD are more likely to develop NAS,especially in ABO incompatible cases.

Donor-derived infections among Chinese donation after cardiac death liver recipients

AIM To investigate blood cultures of deceased donors and report the confirmed transmission of bacterial infection from donors to liver recipients.METHODS We retrospectively studied the results of blood cultures among our donation after cardiac death(DCD) donors and calculated the donor-derived bacterial infection rates among liver recipients. Study participants underwent liver transplantation between January 1, 2010 and February 1, 2017. The study involved a total of 67 recipients of liver grafts from 67 DCD donors. We extracted the data of donors' and patients' characteristics, culture results and clinical outcomes, especially the post-transplant complications in liver recipients, from electronic medical records. We analyzed the characteristics of the donors and the corresponding liver recipients with emphasis put on donor-derived infections.RESULTS Head trauma was the most common origin of death among our 67 DCD donors(46.3%). Blood taken prior to the procurement operation was cultured for 53 of the donors, with 17 episodes of bloodstream infections developing from 13 donors. The predominant organism isolated from the blood of donors was Gram-positive bacteria(70.6%). Only three(4.5%) of 67 liver recipients developed confirmed donor-derived bacterial infections,with two isolates of multidrug-resistant Klebsiella pneumoniae and one isolate of multidrug-resistant Enterobacter aerogenes. The liver recipients with donorderived infections showed relation to higher crude mortality and graft loss rates(33.3% each) within 3 mo post transplantation, as compared to those without donor-derived infections(9.4% and 4.7%, respectively). All three liver recipients received appropriate antimicrobial therapy.CONCLUSION Liver recipients have high occurrence of donor-derived infections. The liver recipients with donor-derived multidrug-resistant Enterobacteriaceae infections can have good outcome if appropriate antimicrobial therapy is given.

Pathological Characteristics of Liver Allografts from Donation after Brain Death Followed by Cardiac Death in Pigs

Donation after brain death followed by circulatory death （DBCD） is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs （25-30 kg） were allocated randomly into donation after brain death （DBD）, donation after circulatory death （DCD） and DBCD groups. Brain death was induced by aug- menting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were col- lected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [（0.56±0.30）%] and DBCD [（0.50 ±0.11）%] groups was much lower than that in DCD group [（3.78±0.33）%] （P〈0.05）. And there was no significant difference between DBD group and DBCD group （P〉0.05））. The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

Liver transplantation with grafts obtained after cardiac death-current advances in mastering the challenge

The scarcity of donor livers has increased the interest in donation after cardiac death(DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusionmodels, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.

Cold ischemia time in liver transplantation:An overview

The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time(CIT).This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time,transit time,and recipient surgery time,and is one of the most important donor-related risk factors which may influence the graft and recipient’s survival.Recently,the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation strategies.This review details the CIT definition and analyzes its different factors.It also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.

Kidney donation after cardiac death

There is continuing disparity between demand for and supply of kidneys for transplantation. This review describes the current state of kidney donation after cardiac death （DCD） and provides recommendations for a way forward. The conversion rate for potential DCD donors varies from 40%-80%. Compared to con-trolled DCD, uncontrolled DCD is more labour intensive, has a lower conversion rate and a higher discard rate. The super-rapid laparotomy technique involving direct aortic cannulation is preferred over in situ perfusion in controlled DCD donation and is associated with lower kidney discard rates, shorter warm ischaemia times and higher graft survival rates. DCD kidneys showed a 5.73-fold increase in the incidence of delayed graft function （DGF） and a higher primary non function rate compared to donation after brain death kidneys, but the long term graft function is equivalent between the two. The cold ischaemia time is a controllable factor that signifcantly infuences the outcome of allografts, for example, limiting it to 〈 12 h markedly reduces DGF. DCD kidneys from donors 〈 50 function like stan-dard criteria kidneys and should be viewed as such. As the majority of DCD kidneys are from controlled dona-tion, incorporation of uncontrolled donation will expand the donor pool. Efforts to maximise the supply of kid-neys from DCD include： implementing organ recovery from emergency department setting; improving family consent rate; utilising technological developments to optimise organs either prior to recovery from donors or during storage; improving organ allocation to ensure best utility; and improving viability testing to reduce primary non function.

Donor preoperative oxygen delivery and post-extubation hypoxia impact donation after circulatory death hypoxic cholangiopathy

AIM: To evaluate donation after circulatory death (DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and donor risk-conditions.METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS DonorNet included preoperative systolic and diastolic blood pressure, heart rate, pH, SpO2, PaO2, FiO2, and hemoglobin. Mean arterial blood pressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O2 content was computed as [hemoglobin (gm/dL) × 1.37 (mL O2/gm) × SpO2%) + (0.003 × PaO2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mmHg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was (ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin.RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age (33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion (9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin (10.7 ± 2.2 gm/dL vs 12.3 ± 2.1 gm/dL, P = 0.017), lower preoperative arterial oxygen content (14.8 ± 2.8 mL O2/100 mL blood vs 16.8 ± 3.3 mL O2/100 mL blood, P = 0.049), greater hypoxia score >2.0 (69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure (92.7 ± 16.2 mmHg vs 83.8 ± 18.5 mmHg, P = 0.10). HC was independently associated with age, multi-pressor/red-cell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure (r2 = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2 (7.1/year)], compared to our early experience [era 1 (2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1 (P = 0.03). Era 2 donors had longer times for extubation-to-asystole (14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia (13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia (16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate (73.1% vs 28.6%, P = 0.006).CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.

Extended criteria brain-dead organ donors:Prevalence and impact on the utilisation of livers for transplantation in Brazil

BACKGROUND Despite its association with higher postoperative morbidity and mortality,the use of extended criteria donor(ECD)livers for transplantation has increased globally due to the high demand for the procedure.AIM To investigate the prevalence of ECD in donation after brain death(DBD)and its impact on organ acceptance for transplantation.METHODS Retrospective analysis of DBD organ offers for liver transplantation between 2017 and 2020 in a high-volume transplant centre.The incidence of the Eurotransplant risk factors to define an ECD(ET-ECD)among DBD donors and the likelihood of organ acceptance over the years were analysed.The relationship between organ refusal for transplantation,the occurrence,and the number of ET-ECD was assessed by simple and multiple logistic regression adjustment.RESULTS A total of 1619 organ donors were evaluated.Of these,78.31%(n=1268)had at least one ET-ECD criterion.There was an increase in the acceptance of ECD DBD organs for transplantation(1 criterion:from 23.40%to 31.60%;2 criteria:from 13.10%to 27.70%;3 criteria:From 6.30%to 13.60%).For each addition of one ETECD variable,the estimated chance of organ refusal was 64.4%higher(OR 1.644,95%CI 1.469-1.839,P<0.001).Except for the donor serum sodium>165 mmol/L(P=0.310),all ET-ECD criteria increased the estimated chance of organ refusal for transplantation.CONCLUSION A high prevalence of ECD DBD was observed.Despite the increase in their utilisation,the presence and the number of extended donor criteria were associated with an increased likelihood of their refusal for transplantation.

Aetiology and risk factors of ischaemic cholangiopathy after liver transplantation

Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient&#x02019;s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.

Critical care specialists,the missing link in organ procurement for transplantation

The procurement process for organ donation begins with the identification of potential organ donors in emergency or critical care units(CCU),followed by their clinical evaluation,diagnostic procedures,and therapeutic interventions,mostly conducted in CCUs.It concludes with the request for organ donation and,if accepted,the retrieval of organs.Despite most interventions occurring in detection units,there has been a neglect of the strategic role played by critical care specialists(CCS)in managing and caring for brain-dead or near-brain-death patients.Questions arise:Are they willing to undertake this responsibility?Do they fully comprehend the nature of organ procurement?Are they aware of the specific interventions required to maintain possible organ donors in optimal physiological condition?Our objective is to examine the role of CCS in organ procurement and propose ways to enhance it,ultimately aiming to increase and enhance organ donation rates.

Acute kidney injury and post-reperfusion syndrome in liver transplantation

In the past decades liver transplantation(LT) has become the treatment of choice for patients with end stage liver disease(ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death(DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease(CKD). Acute kidney injury(AKI) post-LT has been recently recognized as an important risk factor for the occurrence of denovo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome(PRS) that can influence recipient's morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since preLT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A Pub Med search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on Pub Med search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in liver transplantation. In order to identify intra-operative risk factors/mechanisms specifically involved in PRSinduced AKI, avoiding confounding factors, we have limited our study to "acute kidney injury AND DCD AND liver transplantation". Accordingly, three out of five studies were selected for our purpose.

Liver transplantation for a giant mesenchymal hamartoma of the liver in an adult: Case report and review of the literature

Mesenchymal hamartomas of the liver(MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography(CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen includedintraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg(dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months after transplantation, the patient remains well and is fulfilling all normal activities. Adult giant MHL is extremely rare. Symptoms, physical signs, laboratory results, and radiographic imaging are nonspecific and inconclusive. Surgical excision of the lesion is imperative to make a definite diagnosis and as a cure. Liver transplantation should be considered as an option in the treatment of a non-resectable MHL.

Machine perfusion for liver transplantation:A concise review of clinical trials

Background: With the increased use of extended-criteria donors, static cold storage has failed to provide optimal preservation of liver grafts, resulting in early allograft dysfunction and long-term complications Machine perfusion(MP) is a beneficial alternative preservation strategy for donor livers, particularly fo those considered to be of suboptimal quality, and could expand the limited donor pool. Data sources: A comprehensive search in Pub Med, EMBASE, Ovid databases and Clinical Trials.gov website was conducted using the medical subject heading terms "machine perfusion", "machine preservation""liver transplantation", combined with free text terms such as "hypothermic", "normothermic" and "sub normothermic". The deadline for the search was September 30, 2017. Results: MP can be classified as hypothermic, subnormothermic, and normothermic with the tempera ture maintained at 0–12 °C, 25–34 °C and 35–38 °C, respectively. Twelve clinical trials of MP have been reported in recent years. MP effectively decreased AST/ALT level and the incidence of early allograft dys function. However, the graft and patient survival rate after MP were similar to static cold storage. The detailed clinical characteristics such as liver function, graft survival, patient survival and early allograf dysfunction were reviewed.Conclusions: Clinical trial results showed that MP improves delayed graft function, primary non-function and biliary strictures. However, MP still requires validation in large clinical trials and the key parameters during MP still require optimization.

Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant:What is the evidence?

The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.

Severity of early allograft dysfunction following donation after circulatory death liver transplantation:a multicentre study

Background:Early allograft dysfunction(EAD)is associated with decreased graft and patient survival rates.This study aimed to identify the severity of EAD and develop a predictive model for EAD after donation after circulatory death(DCD)liver transplantation(LT).Furthermore,the influence of operative time on EAD incidence was also evaluated.Methods:In this retrospective,multicentre cohort study,nomograms were established based on a single-centre training cohort(n=321)and validated in a 3-center validation cohort(n=501).Results:The incidence rate of EAD was 46.4%(149/321)in the training cohort and 40.5%(203/501)in the validation cohort.Of the 149 EAD patients in the training cohort,77 patients with either elevated alanine aminotransferase(ALT)or aspartate aminotransferase(AST)were classified as having EAD type A,and the rest of the EAD patients were classified as having EAD type B.Recipients with EAD type B had lower graft and patient survival rates than recipients with EAD type A(P=0.043 and 0.044,respectively).We further developed a nomogram to predict EAD(graft weight,cold ischemia time,donor age,model for end-stage liver disease(MELD)score)and another nomogram to predict EAD type B(graft weight,cold ischemia time,MELD score).The nomograms for the prediction of EAD and EAD type B had good discrimination[concordance index(C-index)=0.712(0.666-0.758),0.707(0.641-0.773)]and calibration[Hosmer-Lemeshow(HL)P=0.384,P=0.425]in the validation cohort.An increased operative time(>6 h)was associated with increased EAD and EAD type B incidence in the high-risk group(P=0.005,P=0.020,respectively).Conclusions:EAD type B was associated with decreased graft and patient survival rates.The novel nomograms effectively predicted the incidence of EAD and EAD type B in DCD LT patients.