Search

With the increasing number of accepted candidates on waiting lists worldwide, there is an urgent need to expand the number and the quality of donor livers. Dynamic preservation approaches have demonstrated various benefits, including improving liver function and graft survival, and reducing liver injury and post-transplant complications. Consequently, organ perfusion techniques are being used in clinical practice in many countries. Despite this success, a proportion of livers do not meet current viability tests required for transplantation, even with the use of modern perfusion techniques. Therefore, devices are needed to further optimise machine liver perfusion – one promising option is to prolong machine liver perfusion for several days, with ex situ treatment of perfused livers. For example, stem cells, senolytics, or molecules targeting mitochondria or downstream signalling can be administered during long-term liver perfusion to modulate repair mechanisms and regeneration. Besides, today's perfusion equipment is also designed to enable the use of various liver bioengineering techniques, to develop scaffolds or for their re-cellularisation. Cells or entire livers can also undergo gene modulation to modify animal livers for xenotransplantation, to directly treat injured organs or to repopulate such scaffolds with "repaired" autologous cells. This review first discusses current strategies to improve the quality of donor livers, and secondly reports on bioengineering techniques to design optimised organs during machine perfusion. Current practice, as well as the benefits and challenges associated with these different perfusion strategies are discussed. [ABSTRACT FROM AUTHOR]

While majority of liver transplants worldwide continue to be performed using deceased donor organs, the demands for donor livers continues to exceed the current supply. In an attempt to maximize the number of potentially usable donor livers and expand the current donor pool, there is intense global research by various groups exploring the role of machine perfusion in the liver transplantation, particularly with respect to the machine perfusion of extended-criteria liver donors. In this review, the authors summarize the current field of machine perfusion strategies as applied to deceased donor liver transplantation and how therapeutic targeting of the liver sinusoidal endothelial cell may improve the quality of donor livers. [ABSTRACT FROM AUTHOR]

Introduction Due to the current organ shortage, nearly 20% of patients die waiting for a liver transplant ( LT). The average donor age is on the rise, and grafts from elderly donors are offered as extended criteria grafts. Methods This is a meta-analysis comparing the outcome differences of adult patients undergoing LT using grafts from <70-year-old donors vs >70-year-old donors. The primary end-points were graft and patient survival. Secondary outcomes were biliary and vascular complications as well as graft function. The odds ratio ( OR) is a summary statistic with the corresponding 95% confidence interval; P < .05 was considered to be statistically significant. Results Eight nonrandomized comparative studies with 4376 LT recipients were included. About 79.9% and 20.1% of the grafts were from <70-year-old and >70-year-old donors, respectively. Graft survival at 1 year was similar between the two groups ( P = .11), but there was better 3-year and 5-year graft survival in the >70-year-old group ( P = .006 and P < .0001, respectively). Patient survival was also similar between the groups at 1 year ( P = .54), but with better survival at 3-year and 5-year follow-ups ( P = .007 and P < .0001, respectively) in the >70-year-old group. There were no statistically significant differences in the incidence of biliary, vascular, and graft functional-related complications. Conclusion Liver grafts from selected >70-year-old donors do not pose added organ-specific risks and thus have comparable transplantation outcomes. [ABSTRACT FROM AUTHOR]

Background & Aims: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for liver transplantation in patients with NC-HCC. Methods: Using the European Liver Transplant Registry, we identified 105 patients who underwent liver transplantation for unresectable NC-HCC. Detailed information about patient, tumor characteristics, and survival was obtained from the transplant centers. Variables associated with survival were identified using univariate and multivariate statistical analyses. Results: Liver transplantation was primary treatment in 62 patients and rescue therapy for intrahepatic recurrences after liver resection in 43. Median number of tumors was 3 (range 1–7) and median tumor size 8cm (range 0.5–30). One- and 5-year overall and tumor-free survival rates were 84% and 49% and 76% and 43%, respectively. Macrovascular invasion (HR 2.55, 95% CI 1.34 to 4.86), lymph node involvement (HR 2.60, 95% CI 1.28 to 5.28), and time interval between liver resection and transplantation <12months (HR 2.12, 95% CI 0.96 to 4.67) were independently associated with survival. Five-year survival in patients without macrovascular invasion or lymph node involvement was 59% (95% CI 47–70%). Tumor size was not associated with survival. Conclusions: This is the largest reported series of patients transplanted for NC-HCC. Selection of patients without macrovascular invasion or lymph node involvement, or patients ⩾12months after previous liver resection, can result in 5-year survival rates of 59%. In contrast to HCC in cirrhosis, tumor size is not a predictor of post-transplant survival in NC-HCC. [Copyright &y& Elsevier]

Hepatocellular carcinoma (HCC) arising in noncirrhotic and nonfibrotic liver (NC-HCC) is a rare type of malignancy frequently found in healthy young individuals. Partial liver resection is the treatment of choice with expected 5-year survival rates between 40% and 70%. As a result of absence of any symptom, a considerable number of patients are diagnosed when the malignancy has progressed to an advanced stage and the tumor has turned already unresectable. Some other patients suffer from intrahepatic recurrence after previous liver resection that cannot be re-resected or locally ablated. In these situations, liver transplantation (LT) may be the only potentially curative treatment. The indication for LT in NC-HCC patients, however, is not well established. The preliminary results of recent analysis of the European Liver Transplant Registry (ELTR) together with a literature review identified over 150 patients transplanted for NC-HCC during the last 15 years. In contrast to the historical data, these studies showed 5-year survival rates at 50–70% in well-selected patients. Important determinants of poor outcome are macrovascular invasion, lymph node involvement, and time interval of <12 months when LT is used as rescue therapy for intrahepatic recurrence after a previous partial liver resection. Interestingly, outcomes after both liver resection and LT for NC-HCC are much less influenced by tumor size than is the case with cirrhotic HCC. A large tumor size per se should, therefore, not to be seen as a strict contraindication for performing LT in patients with NC-HCC. [ABSTRACT FROM AUTHOR]

Our study was designed to determine effect of gemcitabine on acute rejection of liver in rats. Liver transplantation was performed in rats of the Dark Agouti (DA) and Lewis (LEW) strains. Recipients were divided into three groups: A, DA-to-LEW without immunosuppression; B, DA-to-LEW, treated with cyclosporine A; C, DA-to-LEW, treated with gemcitabine. Immunosuppressants were subcutaneously injected for seven consecutive days after transplantation. On day 7, blood samples and liver graft tissue specimens were harvested. Group A showed severe rejection changes (RAI 8/9); in group B no rejection changes were present (RAI 0/9), and in group C moderate rejection changes were observed (RAI 6/9). Differences were significant between B vs C and A vs C groups; P<0.05. Serum creatinine and urea levels in the gemcitabine group were significantly lower than those in the cyclosporine A group. We did not confirm gemcitabine ability to prevent liver allograft rejection. [ABSTRACT FROM AUTHOR]

The increasing disparity between the number of patients listed for transplantation and the number of suitable organs has led to the increasing use of extended criteria donors (ECDs). ECDs are at increased risk of developing ischaemia reperfusion injury and greater risk of post-transplant complications. Ischaemia reperfusion injury is a major complication of organ transplantation defined as the inflammatory changes seen following the disruption and restoration of blood flow to an organ—it is a multifactorial process with the potential to cause both local and systemic organ failure. The utilisation of machine perfusion under normothermic (37 degrees Celsius) and hypothermic (4–10 degrees Celsius) has proven to be a significant advancement in organ preservation and restoration. One of the key benefits is its ability to optimise suboptimal organs for successful transplantation. This review is focused on examining ischaemia reperfusion injury and how machine perfusion ameliorates the graft's response to this. [ABSTRACT FROM AUTHOR]

Background: Liver 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. Methods: In 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). Discussion: This 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 registration: ISRCTN ISRCTN14957538. Registered in October 2022. [ABSTRACT FROM AUTHOR]

Liver transplantation is an effective intervention for end-stage liver disease, fulminant hepatic failure, and early hepatocellular carcinoma. Yet, there is marked patient-to-patient variation in liver transplantation outcomes. This calls for novel diagnostics to enable rational deployment of donor livers. Metabolomics is a postgenomic high-throughput systems biology approach to diagnostic innovation in clinical medicine. We report here an original systematic review of the metabolomic studies that have identified putative biomarkers in the context of liver transplantation. Eighteen studies met the inclusion criteria that involved sampling of blood (n = 4), dialysate fluid (n = 4), bile (n = 5), and liver tissue (n = 5). Metabolites of amino acid and nitrogen metabolism, anaerobic glycolysis, lipid breakdown products, and bile acid metabolism were significantly different in transplanted livers with and without graft dysfunction. However, criteria for defining the graft dysfunction varied across studies. This systematic review demonstrates that metabolomics can be deployed in identification of metabolic indicators of graft dysfunction with a view to implicated molecular mechanisms. We conclude the article with a horizon scanning of metabolomics technology in liver transplantation and its future prospects and challenges in research and clinical practice. [ABSTRACT FROM AUTHOR]

Extended duration of normothermic machine perfusion (NMP) provides opportunities to resuscitate suboptimal donor livers. This intervention requires adequate oxygen delivery typically provided by a blood-based perfusion solution. Methaemoglobin (MetHb) results from the oxidation of iron within haemoglobin and represents a serious problem in perfusions lasting > 24 h. We explored the effects of anti-oxidant, N-acetylcysteine (NAC) on the accumulation of methaemoglobin. NMP was performed on nine human donor livers declined for transplantation: three were perfused without NAC (no-NAC group), and six organs perfused with an initial NAC bolus, followed by continuous infusion (NAC group), with hourly methaemoglobin perfusate measurements. In-vitro experiments examined the impact of NAC (3 mg) on red cells (30 ml) in the absence of liver tissue. The no-NAC group sustained perfusions for an average of 96 (range 87–102) h, universally developing methaemoglobinaemia (≥ 2%) observed after an average of 45 h, with subsequent steep rise. The NAC group was perfused for an average of 148 (range 90–184) h. Only 2 livers developed methaemoglobinaemia (peak MetHb of 6%), with an average onset of 116.5 h. Addition of NAC efficiently limits formation and accumulation of methaemoglobin during NMP, and allows the significant extension of perfusion duration. [ABSTRACT FROM AUTHOR]

Background: Liver 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. Methods: In 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). Discussion: This 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 registration: ISRCTN ISRCTN14957538. Registered in October 2022. [ABSTRACT FROM AUTHOR]

Eguchi S, Soyama A, Mergental H, van den Berg AP, Scheenstra R, Porte RJ, Slooff MJH. Honoring the contract with our patients: outcome after repeated re-transplantation of the liver. Clin Transplant 2011: 25: E211-E218. © 2010 John Wiley & Sons A/S. The aim of this study was to describe the outcome after repeated orthotopic liver re-transplantations (re-OLT) in a population of adults and children, and to determine whether such repeated re-transplantations are an effective treatment or should be considered futile. In a consecutive series of 867 patients, 628 adults and 239 children, who underwent OLT at the University Medical Center Groningen, 23 patients (2.7%), 10 adults and 13 children, underwent more than two re-transplantations of the liver between March 1979 and October 2008. All 23 patients had a second re-transplantation, and seven of them received a third transplant. The overall actuarial patient survival at 1, 5, and 10 yr after primary OLT was 96%, 87%, and 71%, respectively. The overall actuarial patient survival after the second re-OLT was 78%, 73%, and 67%, respectively. Sixteen patients (70%) survived long term. However, for the 23 repeated re-transplantation patients, 76 grafts were used. In a simulation calculation, it was shown that honoring the initial commitment to the 23 patients ultimately led to more surviving patients and less death than if treatment of the original patients was stopped after the first re-transplantation and the remaining grafts were allocated to other primary graft recipients. [ABSTRACT FROM AUTHOR]

The combination of hypothermic and normothermic machine perfusion (HMP+NMP) of the liver provides individual benefits of both techniques, improving the rescue of marginal organs. The aim of this study was to investigate the effect on the bioenergetic status and the oxidative-mediated tissue injury of an uninterrupted combined protocol of HMP+NMP using a single haemoglobin-based oxygen carrier (HBOC)-based perfusate. Ten discarded human donor livers had either 2 hours of dual hypothermic oxygenated perfusion (D-HOPE) with sequential controlled rewarming (COR) and then NMP using the HBOC-based perfusate uninterruptedly (cold-to-warm group); or 2 hours of hypothermic oxygenated perfusion (HOPE) with an oxygen carrier-free perfusate, followed by perfusate exchange and then NMP with an HBOC-based perfusate. Markers of liver function, tissue adenosine triphosphate (ATP) levels and tissue injury were systematically assessed. The hypothermic phase downregulated mitochondrial respiration and increased ATP levels in both groups. The cold-to-warm group presented higher arterial vascular resistance during rewarming/NMP (p = 0.03) with a trend of lower arterial flow (p = 0.09). At the end of NMP tissue expression of markers of reactive oxygen species production, oxidative injury and inflammation were comparable between the groups. The uninterrupted combined protocol of HMP+NMP using an HBOC-based perfusate—cold-to-warm MP—mitigated the oxidative-mediated tissue injury and enhanced hepatic energy stores, similarly to an interrupted combined protocol; however, it simplified the logistics of this combination and may favour its clinical applicability. [ABSTRACT FROM AUTHOR]

Hepatic arterial aortic conduits can be used as an alternative means of revascularizing the donor liver when the native recipient hepatic artery (HA) cannot be used. Cytomegalovirus (CMV) is a common Herpesviridae infection in patients who have undergone solid organ transplants. It can be asymptomatic but may cause fever and invasive disease affecting any organ system. Here we describe the first case in the literature of an aortic conduit aneurysm and concurrent CMV viremia following liver transplantation. We speculate on a causative role for CMV in the development of the aneurysm. [ABSTRACT FROM AUTHOR]

Introduction: Pharmacological defatting of rat hepatocytes and hepatoma cell lines suggests that the same method could be used to ameliorate macrovesicular steatosis in moderate to severely fatty livers. However there is no data assessing the effects of those drugs on primary human liver cells. We aimed to determine the effectiveness of a pharmacological cocktail in reducing the in vitro lipid content of primary human hepatocytes (PHH). In addition we sought to determine the cytotoxicity of the cocktail towards non-parenchymal liver cells. Methods: Steatosis was induced in PHH by supplementation with a combination of saturated and unsaturated free fatty acids. This was followed by addition of a defatting drug cocktail for up to 48 hours. The same experimental method was used with human intra-hepatic endothelial cells (HIEC) and human cholangiocytes. MTT assay was used to assess cell viability, triglyceride quantification and oil red O staining were used to determine intracellular lipids content whilst ketone bodies were measured in the supernatants following experimentation. Results: Incubation of fat loaded PHH with the drugs over 48 hours reduced the intracellular lipid area by 54%, from 12.85% to 5.99% (p = 0.002) (percentage of total oil red O area), and intracellular triglyceride by 35%, from 28.24 to 18.30 nmol/million of cells (p<0.001). Total supernatant ketone bodies increased 1.4-fold over 48 hours in the defatted PHH compared with vehicle controls (p = 0.002). Moreover incubation with the drugs for 48 hours increased the viability of PHH by 11%, cholangiocytes by 25% whilst having no cytotoxic effects on HIEC. Conclusion: These data demonstrate that pharmacological intervention can significantly decrease intracellular lipid content of PHH, increase fatty acids β-oxidation whilst being non-toxic to PHH, HIEC or cholangiocytes. [ABSTRACT FROM AUTHOR]

Abstract: Background: Loco‐regional complications of transarterial chemoembolization (TACE) may adversely affect technical aspects of the liver transplantation (LT). This study reviewed the impact of those complications on postoperative outcomes encompassing implications on graft selection. Methods: A retrospective, propensity score matching (1:1) analysis accounting for donor and recipient confounders was performed on a dataset of patients undergoing LT for hepatocellular carcinoma. Outcomes of patients who had TACE (TACE‐group) were compared with those who did not (NoTACE‐group). Results: A total of 57 matched pairs were analyzed. TACE achieved effective tumor control (Pre‐TACE vs Post‐TACE; Median: 44 mm [interquartile range: 43‐50] vs 17 mm [0‐36]; P = .002) on imaging follow‐up. TACE group had, at the hepatectomy, higher incidence of ischemia‐related complications (adhesions of the necrotic tumor, cholecystitis, and/or bile duct necrosis) (40.4% vs 10.5%; P = .001). Overall major post‐LT complications rate (Dindo‐Clavien ≥3) were similar (P = .134). Those in the TACE group with donors after circulatory death (DCD) had 4.6% 90‐day mortality and 54.3% major complication rate compared to 6.9% and 77.3% (P = .380 and P = .112, respectively). Conclusion: TACE was an effective bridging procedure that may complicate LT inducing ischemic‐related complications; nevertheless, it has not shown repercussions on mortality or morbidity after the procedure, even using donors after circulatory death. [ABSTRACT FROM AUTHOR]

Background & Aims Primary non-function and ischaemic cholangiopathy are the most feared complications following donation-after-circulatory-death (DCD) liver transplantation. The aim of this study was to design a new score on risk assessment in liver-transplantation DCD based on donor-and-recipient parameters. Methods Using the UK national DCD database, a risk analysis was performed in adult recipients of DCD liver grafts in the UK between 2000 and 2015 (n = 1,153). A new risk score was calculated (UK DCD Risk Score) on the basis of a regression analysis. This is validated using the United Network for Organ Sharing database (n = 1,617) and our own DCD liver-transplant database (n = 315). Finally, the new score was compared with two other available prediction systems: the DCD risk scores from the University of California, Los Angeles and King’s College Hospital, London. Results The following seven strongest predictors of DCD graft survival were identified: functional donor warm ischaemia, cold ischaemia, recipient model for end-stage liver disease, recipient age, donor age, previous orthotopic liver transplantation, and donor body mass index. A combination of these risk factors (UK DCD risk model) stratified the best recipients in terms of graft survival in the entire UK DCD database, as well as in the United Network for Organ Sharing and in our own DCD population. Importantly, the UK DCD Risk Score significantly predicted graft loss caused by primary non-function or ischaemic cholangiopathy in the futile group (>10 score points). The new prediction model demonstrated a better C statistic of 0.79 compared to the two other available systems (0.71 and 0.64, respectively). Conclusions The UK DCD Risk Score is a reliable tool to detect high-risk and futile combinations of donor-and-recipient factors in DCD liver transplantation. It is simple to use and offers a great potential for making better decisions on which DCD graft should be rejected or may benefit from functional assessment and further optimization by machine perfusion. Lay summary In this study, we provide a new prediction model for graft loss in donation-after-circulatory-death (DCD) liver transplantation. Based on UK national data, the new UK DCD Risk Score involves the following seven clinically relevant risk factors: donor age, donor body mass index, functional donor warm ischaemia, cold storage, recipient age, recipient laboratory model for end-stage liver disease, and retransplantation. Three risk classes were defined: low risk (0–5 points), high risk (6–10 points), and futile (>10 points). This new model stratified best in terms of graft survival compared to other available models. Futile combinations (>10 points) achieved an only very limited 1- and 5-year graft survival of 37% and less than 20%, respectively. In contrast, an excellent graft survival has been shown in low-risk combinations (≤5 points). The new model is easy to calculate at the time of liver acceptance. It may help to decide which risk combination will benefit from additional graft treatment, or which DCD liver should be declined for a certain recipient. [ABSTRACT FROM AUTHOR]

Introduction: Hepatocellular carcinoma (HCC) is increasing in incidence in the UK and globally. Liver cirrhosis is the common cause for developing HCC. The common reasons for liver cirrhosis are viral hepatitis C (HCV), viral hepatitis B and alcohol. However, HCC caused by non-alcoholic fatty liver disease (NAFLD)-cirrhosis is now increasingly as a result of rising worldwide obesity. Aim: To compare the clinical presentation, treatment options and outcomes of HCC due to HCV and NAFLD patients. Methods: Data were collected from two liver transplant centres in the UK (Birmingham and Newcastle upon Tyne) between 2000 and 2014. We compared 275 patients with HCV-related HCC against 212 patients with NAFLD-related HCC. Results: Patients in the NAFLD group were found to be significantly older (P < 0.001) and more likely to be Caucasian (P < 0.001). They had lower rates of cirrhosis (P < 0.001) than those in HCV-HCC group. The NAFLD group presented with significantly larger tumours (P = 0.009), whilst HCV patients had a higher alpha fetoprotein (P = 0.018). NAFLD patients were more commonly treated with TACE (P = 0.005) than the HCV patients, whilst the HCV group were significantly more likely to be transplanted (P < 0.001). In patients selected for liver transplantation, 5-year survival rates in NAFLD were not significantly different from HCV-HCC (44 and 56% respectively, P = 0.102). Conclusion: In this study, NAFLD patients presented with larger tumours that were less likely to be amenable to curative therapy, as compared with HCV patients. Despite this disadvantage, patients with NAFLD had similar overall survival compared to patients with HCV. [ABSTRACT FROM AUTHOR]

Hepatic venous outflow obstruction ( HVOO) is a rare complication after liver transplantation ( LT) associated with significant morbidity and reduced graft survival. Endovascular intervention has become the first-line treatment for HVOO, but data on long-term outcomes are lacking. We have analysed outcomes after endovascular intervention for HVOO in 905 consecutive patients who received 965 full-size LT at our unit from January 2007 to June 2014. There were 27 (3%) patients who underwent hepatic venogram for suspected HVOO, with persistent ascites being the most common symptom triggering the investigation ( n = 19, 70%). Of those, only 10 patients demonstrated either stricture or pressure gradient over 10 mmHg on venogram, which represents a 1% incidence of HVOO. The endovascular interventions were balloon dilatation ( n = 3), hepatic vein stenting ( n = 4) and stenting with dilatation ( n = 3). Two patients required restenting due to stent migration. The symptoms of HVOO completely resolved in all but one patient, with a median follow-up period of 74 (interquartile range 39-89) months. There were no procedure-related complications or mortality. In conclusion, the incidence of HVOO in patients receiving full-size LT is currently very low. Endovascular intervention is an effective and safe procedure providing symptom relief with long-lasting primary patency. [ABSTRACT FROM AUTHOR]

Impact of performing multiple liver transplants ( LT) in a short period of time is unknown. Consecutively performed LT potentially increase complication rates through team fatigue and overutilization of resources and increase ischemia time. We analyzed the impact of undertaking consecutive LT (Consecutive liver transplant, CLT; LT preceded by another transplant performed not more than 12 h before, both transplants grouped together) on outcomes. Of 1702 LT performed, 314 (18.4%) were CLT. Outcome data was compared with solitary LT ( SLT; not more than one LT in 12-h period). Recipient, donor, and graft characteristics were evenly matched between SLT and CLT; second LT of CLT group utilized younger donors grafts with longer cold ischemic times ( P = 0.015). Implantation and operative time were significantly lower in CLT recipients on intergroup analysis ( P = 0.0001 and 0.002, respectively). Early hepatic artery thrombosis (E- HAT) was higher in CLT versus SLT ( P = 0.038), despite absolute number of E- HAT being low in all groups. Intragroup analysis demonstrated a trend toward more frequent E- HAT in first LT, compared to subsequent transplants; however, difference did not reach statistical significance ( P = 0.135). In era of organ scarcity, CLT performed at high-volume center is safe and allows pragmatic utilization of organs, potentially reducing number of discarded grafts and reducing waiting list mortality. [ABSTRACT FROM AUTHOR]

Background & Aims We studied new-onset diabetes after transplantation ( NODAT) in liver transplantation with grafts donated after brain death ( DBD) or circulatory death ( DCD), focusing on the early post-transplant period. Methods A total of 430 non-diabetic primary liver transplant recipients [ DCD, n = 90 (21%)] were followed up for 30 months (range 5-69). NODAT was defined as the composite endpoint of one of following: (i) Two non-fasting plasma glucose levels > 11.1 mmol/L ≥ 30 days apart, (ii) oral hypoglycaemic drugs ≥ 30 days consecutively (iii) insulin therapy ≥ 30 days and (iv) HbA1c ≥ 48 mmol/L. Resolution of NODAT was defined as cessation of treatment or hyperglycaemia. Results Total of 81/430 (19%) patients developed NODAT. Incidence and resolution of NODAT over time showed significantly different patterns between DCD and DBD liver graft recipients; early occurrence, high peak incidence and early resolution were seen in DCD. In multivariate logistic regression including age, ethnicity, HCV, tacrolimus level and pulsed steroids, only DCD was independently associated with NODAT at day 15 post-transplant ( OR 6.5, 95% CI 2.3-18.4, P < 0.001), whereas age and pulsed steroids were significant factors between 30-90 days. Combined in multivariate Cox regression model for NODAT-free survival, graft type, age and pulsed steroids were each independent predictor for decreased NODAT-free survival in the first 90-postoperative days. Conclusion Early peak of NODAT in DCD graft recipients is a novel finding, occurring independently from known risk factors. Donor warm ischaemia and impact on insulin sensitivity should be further studied and could perhaps be associated with graft function. [ABSTRACT FROM AUTHOR]

Liver ischaemia–reperfusion injury (IRI) is an intrinsic part of the transplantation process and damages the parenchymal cells of the liver including hepatocytes, endothelial cells and cholangiocytes. Many biomarkers of IRI have been described over the past two decades that have attempted to quantify the extent of IRI involving different hepatic cellular compartments, with the aim to allow clinicians to predict the suitability of donor livers for transplantation. The advent of machine perfusion has added an additional layer of complexity to this field and has forced researchers to re-evaluate the utility of IRI biomarkers in different machine preservation techniques. In this review, we summarise the current understanding of liver IRI biomarkers and discuss them in the context of machine perfusion. [ABSTRACT FROM AUTHOR]