Liver Transplant Complications

A prospective, open-label, single-arm, investigator-initiated study (SELIC) to evaluate the efficacy and safety of seladelpar in adult liver transplant recipients with Ischemic cholangiopathy (IC).

The purpose of this study is to assess the safety of autologous Adipose-Derived Mesenchymal Stem Cell for use in End-Stage Liver Disease patients undergoing the creation of a duct-to-duct anastomosis during Living Donor Liver Transplantation.

Liver transplantation (LT) is a surgery with risk of bleeding. Several risk factors have been identified: complex dissection, portal hypertension, history of ascites fluid infections, history of surgical procedures, pre-existing complex hemostatic disorders and those acquired during the procedure. Diffuse bleeding can occur at any time during the 3 phases of surgery: dissection, anhepatic and neohepatic. However, intraoperative bleeding and transfusion requirements remain difficult to predict. Current predictive models are based in particular on preoperative characteristics and do not take into account the course and different phases of the operation. The need for transfusions has largely decreased over the last 20 years, and currently around 20-25% of patients are transfused (transfusion of at least 1 blood product during LT). However, massive transfusion is necessary in 10% of LT. The European Society of Anaesthesiology (ESA) has issued recommendations on the management of severe bleeding during surgery. However, these recommendations are not specific to LT. Moreover, transfusion strategies vary widely from one center to another. The implementation of protocols within teams dedicated to LT has led to a reduction in bleeding and transfusion, with or without the use of viscoelastic testing. Intraoperative bleeding and transfusion requirements, as well as postoperative thromboembolic complications, remain difficult to predict. Predictive models of bleeding risk have been developed, but they are based solely on preoperative characteristics and do not take into account the course and various phases of the operation. In addition, new methods such as Bayesian inference or machine learning have been developed, and seem capable of providing different information from that obtained by conventional models. The overall aim of this prospective multicenter observational study is to investigate the risk factors for bleeding and thrombosis in per- and post-operative LT using different predictive methods, and to describe the management of bleeding and post-operative anticoagulation in metropolitan France.

The aim of the study is to improve the results of related transplantation of the right liver lobe by verifying the general predictors of the development of hemostatic system disorders and optimizing a comprehensive program for thrombohemorrhagic complications preventing.

This study is being done to find out if administering CytoGam® after the end of standardly prescribed preventive antiviral treatment can help transplant recipients with a high risk for developing late CMV disease after a liver and/or kidney transplant.

This is a national multicenter, randomized clinical trial to evaluate the the efficacy and safety of DP administration in patients on the liver transplant waiting list to reduce intraoperative red blood cell concentrate transfusion.

Management of ACLF is mainly supportive. The poor outcomes lead physicians to consider liver transplantation as an option, even if controversial. In sicker recipients, LT results in immediate survival, but poor medium-term survival rates in some studies. The scarcity of deceased donors obliges to maximize LT success. Alternative strategies, as living-donor LT, should be explored. LDLT has impressive results in Eastern centers, but it is restrained in Western countries, due to potential life-threatening complications in the donor.

Registry intended to provide a data repository and reporting infrastructure for the surveillance of CytoSorb device use in real-world critical care settings, and to serve as an objective, comprehensive, and scientifically-based resource to measure and improve the quality of patient care

Medications used after transplant to prevent rejection are associated with many side effects. Tacrolimus side effects include kidney dysfunction; tremor, headaches, difficulty sleeping, change in sensation (legs), seizure, or confusion; high blood pressure; anemia, or low blood cell counts; diabetes; abnormal cholesterol and weight gain. The investigators want to use a new, approved, formulation of the standard medication (Envarsus) as they believe it may be associated with reduced side effects. The investigators would like to assess how safe it is to use this medication and how well it works in comparison to currently used formulations. The investigators will study if there are less side effects and will study clinical outcomes (including how well the liver does and if there is need for hospitalizations after transplant). The investigators hope that this information will improve the care provided to and outcomes in patients following liver transplant.

The Health Advocate for Liver Transplant (HEAL-Tx) Pilot is a nonrandomized, open-label intervention pilot of a health advocate intervention aimed to assess feasibility and acceptability of integrating a Health Advocate onto the transplant team. Across studies, health advocate roles vary, and can include coordinating medical care treatment, facilitating financial assistance (e.g., taxi vouchers), and connecting patients to community resources, which can improve self-management, mitigate social risks, and lead to better communication between the healthcare system and the family. In this pilot, the investigators will adapt this intervention for pediatric liver transplant patients and measure acceptability and feasibility according to RE-AIM.

This prospective, open-label, randomized controlled trial aims to evaluate the efficacy of intravenous amino acid infusion in reducing AKI after LDLT. Eligible adult patients undergoing LDLT will be randomized into two groups: one receiving Continuous infusion of a L-amino acids mixture in a dose of 2 g/kg dry body weight/day (to a maximum 100 g/day) after induction of anesthesia and insertion of CVP line till 72 hours after treatment initiation, and the other receiving standard management. The primary outcome is the incidence of AKI as per KDIGO criteria within 7 days of transplant.

Liver transplantation is an effective method for treating end-stage liver disease and metabolic diseases in children. With the advancement of surgical techniques and the improvement of perioperative management, the survival rates of patients and grafts after liver transplantation have significantly improved. However, the complication of biliary stenosis after transplantation is as high as 7.3% -33.3%, and in severe cases, it can even lead to graft failure and patient death. Therefore, the occurrence of biliary stenosis after liver transplantation seriously affects the quality of life of children, increases the economic burden on families, and urgently needs to find effective methods to reduce the occurrence of this complication. Based on the clinical practice of our center, we believe that the placement of biliary external drainage stents has the following advantages: 1 Reduce intrahepatic biliary pressure and reduce the occurrence of postoperative biliary fistula; 2. The stent has a supporting effect and can maintain the open state of the bile duct; 3. By external drainage, the quality of bile secretion by the liver can be evaluated; 4. Provide a pathway for cholangiography. However, placing external biliary drainage may also pose certain risks, including increasing surgical procedures, stent detachment causing biliary fistula, and increasing the risk of infection. This study aims to observe the effect of placing external biliary drainage stents on biliary stricture after liver transplantation in children. The aim is to evaluate the preventive effect of external biliary drainage stents on biliary intestinal anastomotic stenosis after liver transplantation in children, and to provide evidence-based evidence for reducing biliary complications in children.

To define the sensibility and the specificity of increased levels of MR-proADM for early, non-invasive, diagnosis of AR and DGF after kidney and liver transplantation creating a predictive model for related complications after kidney and liver transplantation based on the pre-operative and post-operative levels of MR-proADM and by a machine learning process.

Liver transplantation (LT) is a live-saving therapy for patients with complicated chronic liver diseases and acute liver failure .Even though many complications can occur after LT, biliary complications (BC) are both common and potentially severe . a prospective study and retrospective part from hospital records. Aim of the study: 1. Detect frequency, risk factors for development of biliary complications post living donor liver transplantation, types (stricture anastomotic or not, leak, biloma, stone, cholangitis etc.…). 2. Evaluate outcomes of different biliary complications

This study aims to determine the efficacy of 36 months once-daily fenofibrate in preventing clinically-detectable recurrence of primary sclerosing cholangitis after liver transplantation, compared with a historical control cohort that was not treated with

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions ranging from liver steatosis (NAFL), steatohepatitis (NASH), advanced liver fibrosis and ultimately leads to cirrhosis in a significant proportion of individuals. NAFLD is intimately associated with insulin resistance and associated disorders, such as obesity, type 2 diabetes, metabolic syndrome, and dyslipidemia. It has been noted that several individuals with liver transplantation develop nonalcoholic fatty liver disease in the transplanted liver. This is because of the presence of various risk factors of obesity and NAFLD, such as decreased physical activity, that persist following liver transplantation. Post-liver transplant patients are particularly at risk for developing NAFLD, as these patients are on oral steroids and immunosuppressants for a significant period of time. There is no medication approved for the prevention or treatment of NAFLD. Semaglutide is an GLP-1 receptor agonist that have been approved for the treatment of type 2 diabetes and obesity. Semaglutide has also been demonstrated to have beneficial effects on NAFLD. However, there is no data on the effect of semaglutide on liver fat accumulation or changes in body composition in patients following liver transplantation. Therefore, the current pilot study is planned to evaluate the effect of oral semaglutide on the liver fat, liver enzymes and body composition in patients undergoing liver transplantation

The Health Advocate for Liver Transplant (HEAL-Tx) Transition of Care Pilot is a nonrandomized, open-label intervention pilot of a health advocate intervention aimed to assess feasibility and acceptability of integrating a Health Advocate onto the transplant team to help adolescents transition their care to adult transplant teams. Across studies, health advocate roles vary, and can include coordinating medical care treatment, facilitating financial assistance (e.g., taxi vouchers), and connecting patients to community resources, which can improve self-management, mitigate social risks, and lead to better communication between the healthcare system and the family. In this pilot, the investigators will adapt this intervention for adolescent/young adult liver transplant patients and measure acceptability and feasibility according to RE-AIM.

The objective of this study is to determine the feasibility and effectiveness of a home-based multimodal prehabilitation program in patients anticipated to be waitlisted for LT. Patients will participate in an eight week prehabilitation program consisting of physical exercise, nutritional support, smoking cessation and psychological counselling.

Biliary complications after liver transplantation (LT) remain common and are associated with higher morbidity in liver transplant recipients and liver graft failure. Anastomotic biliary strictures are the most common biliary strictures after LT. Today, the gold standard for treatment remains endoscopic retrograde cholangiopancreatography (ERCP) with either multiple plastic stenting (MPS) or fully covered metal stents. These methods have disadvantages such as the need for repeated ERCP procedures, high costs or the risk of migration. Biodegradable stents (BDS) are a novel type of stents made from various synthetic polymers or their copolymers, which are now being used in a variety of medical fields, including the pancreatobiliary tract.The use of biodegradable stents has shown good potential in the treatment of benign biliary strictures. However, overall data on their endoscopic use in liver transplant recipients, particularly in the treatment of anastomotic biliary strictures, are scarce. Most studies have either been in animal models, using percutaneously implanted stents, or in non-transplanted patients. There are no randomised controlled trials investigating their use in LT patients. Based on the available evidence, the use of BDS in the treatment of anastomotic biliary strictures in liver transplant recipients appears to be a promising technique that may be as effective as the standard treatment with MPS, but may reduce the number of ERCP procedures and eliminate the risk of migration. The aim of this randomised prospective study is to compare the difference in rates of anastomotic stricture resolution between the active (BDS) and control (MPS) groups to demonstrate non-inferiority of the biodegradable stents. Outcomes will be classified as complete resolution (no significant stricture at the anastomotic site on imaging and resolution of cholestasis), significant response (relative stricture and resolution of cholestasis) or failure (persistent stricture and/or persistent cholestasis). Secondary outcomes are technical feasibility, immediate and late complications.

The main objective of the trial is to compare the effect of two end-to-end duct-to-duct anastomosis surgical techniques using the continuous suture method versus interrupted method (control group) on reducing the risk of bile leakages in the 90-day follow-up period after liver transplantation and other postoperative complications resulting from them i.e.: the occurrence of a critical stenosis in the duct-to-duct anastomosis within 90 days. In addition, as part of the research experiment, long-term biliary complications will be assessed, i.e. occurring over a period of more than 90 days (a 2-year observation period of patients was assumed). As part of the trial 284 patients qualified for the procedure of liver transplantation from a deceased donor will be included, in whom end-to-end anastomosis of the bile ducts will be performed. After entering the study, patients will be randomized to one of the groups. In the group of 142 patients, duct-to-duct anastomosis will be performed using an interrupted suture (control group), and the remaining patients will be performed using the continuous suture technique. The analysis will also include surgical complications, complications related to early and late graft function, retransplantation and overall survival. Additionally the analyses an analysis of the impact of the occurrence of a biliary complication on the quality of life of patients after liver transplantation will be performed on the basis of the EORTC QLQ-C30 forms. The period of observation of the patient after the procedure is planned for 24 months.

The prevalence of chronic liver disease and primary liver cancer is still increasing on a global scale, and so are their associated deaths. Compared to other diseases, death from liver disease often means premature death, because two-thirds of the lives lost are working years. Liver transplantation (LT) is an important and life-saving treatment option for the treatment of congenital metabolic disorders, acute liver failure, end-stage chronic liver disease (ESLD) and primary liver cancers. Modern liver transplantation is characterized by significant improvements in post-transplant patient survival, graft survival, and quality of life. Impaired physical fitness of patients with end-stage liver disease often persists after liver transplantation and compromises post-transplant recovery. Prior to liver transplantation, excess ammonia taken up by skeletal muscle is a major metabolic driver of muscle wasting in end-stage liver disease and mainly inhibits the mTOR signaling pathway that supports muscle protein synthesis. Because excess ammonia is no longer present after transplantation, recovery of muscle mass and function can be expected in patients. However, immunosuppression with calcineurin inhibitors that inhibit the mTOR signaling pathway may improve lethal length. It is also thought that post-transplant treatment regimens contribute to delayed recovery of decreased bone mineral density and increased fracture risk. Greater muscle mass, as measured by creatinine clearance at 1 year after transplantation, was associated with longer recipient and allograft survival. The results of previous studies indicate low cardiovascular fitness in patients after liver transplantation. Since after liver transplantation, cardiovascular diseases cause 19 to 42% of deaths not related to the liver, performing aerobic exercises to obtain and maintain cardiovascular fitness after liver transplantation can reduce the mortality rate. After transplanting, reduced significantly. Considering the important role of the immune system in transplant rejection, the safety of sports training is very important in terms of not over-activating the immune system and endangering the life of the transplanted tissue. In previous studies related to exercise and immune system activity and inflammatory cytokines after transplantation, it has been shown that moderate exercise including aerobic and resistance exercises can inhibit inflammatory cytokines and have beneficial effects on the immune system. High levels of tumor necrosis factor-alpha (TNF-α) in the period after transplant surgery are associated with an increased risk of transplant rejection. Aerobic exercise reduces levels of inflammatory cytokine TNF-α and markers of liver function in patients with chronic liver diseases. According to this evidence, it seems that doing sports exercises is effective in reducing the risk of transplant rejection and modulating the patient's immune system. Acute graft rejection occurs days to weeks after transplantation. The immune system can see the transplanted organ as foreign and attack it, destroy it and lead to transplant rejection. Considering the mentioned benefits of exercise therapy after liver transplantation, it is possible that the early start of exercise therapy in the hospitalization phase leads to a reduction in the risk of transplant rejection and improvement of allograft residues in patients after liver transplantation. Considering that the current evidence shows that there is no use of a specific rehabilitation protocol in the hospitalization phase of patients after liver transplantation, we intend to evaluate its effects with changes in the common physiotherapy program in these departments according to the specific conditions of these patients. In other words, despite the acceptable therapeutic effects, the use of a combined protocol of aerobic and resistance exercises in the hospitalization phase of these patients has not been reported so far.

Liver transplantation in children is highly successful with \>80% having 20 years survival. Most pediatric liver diseases are potentially curable with liver transplantation and it is important to establish whether children who have undergone successful transplantation can expect a normal life expectancy or whether there will be a gradual decline in liver function and eventual graft loss. The most common reasons in late graft loss in children are unexplained graft inflammation ("idiopathic" post-transplant hepatitis) and graft fibrosis. PRO-C3, a disintegrin and metalloproteinase with thrombospondin motifs-generated neo-epitope marker of type III collagen formation, has been proved to be a marker of fibrosis in patients with NAFLD. The aim of this study is to explore the role of Fibrosis Panel(PRO-C3, PIIINP, TIMP-1, HA) in children received liver transplantation.

a prospective cohort study comparing outcomes of left lobe and right lobe adult living donor liver transplantation

This clinical trial evaluated the safety, tolerability, pharmacokinetic properties, and immunogenicity of DNP007 when administered as a single dose. Since this is a phase 1 study for exploratory evaluation, to the extent that it meets the study objectives, In order to proceed with the minimum number of subjects, a total of 12 people, 3 for each dose group, was planned as the target number.

The use of devices for liver grafts perfusion before transplantation, either hypothermic (HOPE) or normothermic (NMP), is rapidly spreading thanks to the promising results obtained so far in terms of graft survival and post-operative morbidity. Besides the well-established ability to increase the rate of transplantability of extended criteria donors (ECD) and donors after cardiac death (DCD), the use of machine perfusion (MP) may also improve the oncological outcomes of patients affected by hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). The underlying mechanism is represented by the modulation of the ischemia-reperfusion injury (IRI)-related cellular damage obtained by the liver graft perfusion with HOPE before LT. The identification of biomarkers able to predict graft outcomes and highlight the mechanism of graft injury before transplantation rapidly and in non-invasive manner is therefore needed. Mass spectrometry-based metabolomics has already shown its potential by using perfusion liquids or pre-implantation biopsies. The aim of the investigators is to run an open-label, randomised, controlled trial to study the impact of treating standard liver grafts from brain dead donors (DBD) with HOPE before liver transplant in patients affected by HCC. Patients aged 18-75 years presenting with HCC Milan-in at listing will be considered for inclusion. Presence of extra-hepatic disease and general contraindications to liver transplantation as defined by the local tumor board are considered as exclusion criteria. Eligible patients will be randomly assigned (1:1) with the use of a dedicated software to MP (intervention group) or no-MP (control group) before liver transplantation. Untargeted mass spectrometry metabolomics (UHPLC-HRMS) will be performed on liver graft perfusate, liver graft biopsy and recipient blood samples, to identify by classification methods, novel predictive markers of IRI. Furthermore, rapid targeted MS approaches will be performed on VIP metabolites and known key compounds (such as TCA, aminoacids, energy metabolism) to rapidly assess graft function as well as post-operative outcome. Blood samples of the recipient will be collected at two checkpoints (listing, and 3 months after liver transplant) to evaluate exosomes and miRNA expression fluctuations (liquid biopsy). Primary outcomes of the study will be overall survival, graft survival and recurrence-free survival at 1- and 2-years. Survival results will be compared to those expected based on the Metroticket 2.0 score to assess the impact of MP in reducing the risk of HCC recurrence. Patients will remain in follow-up as for clinical practice to assess 3- and 5-years survival. Secondary end-point will be to define liquid biopsy efficacy to predict HCC recurrence and to define the correlation between metabolomic observations and HCC recurrence pattern.