Clinical Research Directory

Establishing a Reference Framework for Outcomes After Machine-Preserved Liver Transplantation in Europe

Machine perfusion (MP) has become routine clinical practice in liver transplantation. However, as the field has matured, direct randomized comparisons between distinct MP modalities have become increasingly impractical, given that donor and graft characteristics often predetermine the optimal preservation strategy. Consequently, many studies continue to reference historical benchmark cohorts from the pre-perfusion era, or use risk scores developed before routine utilization of MP. These cohorts, while once valuable, fail to account for the paradigm shift that MP has introduced. Likewise, commonly used donor- and recipient-based risk scores were developed prior to the adoption of MP. While these scores aim to assess survival or morbidity after transplantation, none of them guide decisions about MP use or the most suitable perfusion protocol. As MP technologies continue to evolve there is a critical need for an updated reference framework that accurately reflects current clinical practice and captures the best achievable outcomes across all MP modalities.

Rejection After Auxiliary Partial Orthotopic Liver Transplantation: An Exploratory Comparison by Native-Liver Cirrhosis Status

This retrospective single-center cohort study aims to investigate the association between native-liver cirrhosis status and post-transplant outcomes in recipients undergoing auxiliary partial orthotopic liver transplantation (APOLT). A total of 44 recipients who underwent APOLT between 2014 and 2025 will be included and classified into non-cirrhotic and cirrhotic groups according to the histopathological findings of the retained native liver. The study will compare biopsy-proven rejection, including first and recurrent rejection episodes, postoperative complications, overall survival, and graft survival between the two groups. The findings may help improve understanding of the relationship between native-liver cirrhosis status and post-transplant outcomes and provide evidence for future clinical research and individualized post-transplant management.

Impact of a Risk Stratification Tool on the Outcome of Liver Transplant Recipients Colonized With Carbapenem Resistant Enterobacteriaceae: an Observational Study

Although CRE infection after OLT have a dramatic impact on patient survival and several implementations have been proposed (i.e. preventive strategies or targeted surgical prophylaxis), a standardized approach in colonized patients is still missing. The investigators recently developed and internally validated a bed-side score to stratify the risk of CRE infection in OLT recipients colonized by CRE. The goal of this pre/post observational study is to investigate the impact on all-cause 90-day mortality in OLT recipients colonized with CRE using such score (CRECOOLT score) for the systematic evaluation of CRE infection risk. The secondary objectives are: * To analyse days of therapy with anti-CRE antibiotic regimens in patients with and without systematic evaluation of CRE infection risk, according to clinical practices. * To evaluate rates of documented CRE infections and their relapses with selection of further resistance in patients with and without systematic evaluation of CRE infection risk. * To evaluate the length of hospital, ICU stay and rates of hospital readmission in patients with and without systematic evaluation of CRE infection risk.

Study to Compare the Pharmacokinetics of Tacrolimus in Stable Pediatric Allograft Recipients Converted From Prograf® to Advagraf®

Parts A \& B: Conversion of stable pediatric allograft recipients from Prograf® immunosuppression to Advagraf® immunosuppression to compare exposure and one year follow-up for safety and efficacy. Part C: Continuation of long-term follow-up and provision of ongoing study medication to subjects to whom Advagraf® is currently not available.

Everolimus bAsed caLcineurin inhibiTor frEe immunosuppRession oNe Year AfTer lIver transplantatiON (ALTERNATION)

The overall aim of this study is nephroprotection based on a calcineurin inhibitor (CNI)-free therapy beyond year one after orthotopic liver transplantation (OLT) in highly pre-selected patients with low rejection risk.

Effects of Donor and Recipient Genetic Expression on Heart, Lung, Liver, or Kidney Transplant Survival

Activity of genes in donor tissues that are involved in inflammation are thought to be involved with early organ dysfunction, increased immune responses in transplant recipients, and organ rejection. The purpose of this study is to determine the relationship between genetic expression in donor and recipient tissue with transplant survival. Participants in this study will have received heart, lung, liver, or kidney transplants.

Discovery and Validation of Proteogenomic Biomarker Panels in Liver Transplant Recipients

The main focus of this study is to develop blood and/or urine tests that will help to detect early signs of rejection in people who have had a liver transplant. Researchers will examine blood, urine, and tissue samples and try to identify markers for certain conditions such as rejection, response to therapy, and scarring of the liver. Additionally, researchers would like to identify biomarkers that can detect damage to the native kidneys before blood levels of creatinine rises. By studying gene expression, researchers hope to be able to diagnose these conditions earlier and improve liver survival.

Gene Expression in Liver Allograft Rejection and Recurrent Hepatitis C

Acute cellular rejection is relatively common after liver transplantation, typically does not affect graft survival, and is not associated with the development of chronic rejection. Acute cellular rejection is diagnosed when liver enzymes and/or liver function tests are elevated when compared to baseline. The only means of differentiating acute rejection from other liver pathologies is with a liver biopsy. However, even with this invasive diagnostic procedure, it may be difficult to distinguish acute rejection from another disease process, such as injury caused by the hepatitis C virus (HCV) from the native liver. This study will evaluate whether certain patterns of biomarkers in the peripheral blood and/or liver tissue of a liver transplant recipient can be used to determine if the transplanted liver is being rejected by the recipient or sustaining HCV injury. Diagnostic biomarkers that are specific for acute rejection and informative of the severity of HCV recurrence could allow for modulation of immunosuppression therapy and treat the clinical condition without the need for invasive liver biopsies.

Molecular Assessment and Profiling of Liver Transplant Recipients

The objective of this protocol is to conduct longitudinal and prospective studies of liver transplant recipients, using a multimodality approach, akin to that used in kidney transplantation. The primary aim will compare the clinical outcomes of LiverCare post-transplant surveillance in liver transplant with standard of care consisting of liver function tests, DSA measurements, drug level monitoring, and 'for cause' biopsy. The protocol will assess the correlation between clinical events (e.g. rejection, recurrent disease, biliary obstruction), dd-cfDNA levels, gene expression profiling, ability to assess microchimerism, develop predictive analytics, infectious disease diagnoses and finally examine graft histology.

Open Label Trial of Deceased Donor Livers Transplanted After DHOPE With eXVIVO LIVER Perfusion

The purpose of this clinical study is to confirm the safety and effectiveness of dual hypothermic oxygenated perfusion (DHOPE) using the Liver Assist to preserve deceased donor livers for transplantation.

Reducing Pain With Methadone and Ketamine in Liver Transplant

The goal of this clinical trial is to learn if using methadone and ketamine during an adult deceased donor liver transplant can help decrease pain after surgery. The main questions it aims to answer are: * What impact does using methadone and ketamine during a deceased donor liver transplant have on pain after surgery? * Does the use of methadone and ketamine also have an impact on mental confusion (delirium) after surgery? Researchers will compare the use of methadone and ketamine to standard of care to see if the two drugs work to decrease pain and impact delirium after liver transplant. Participants will: * Receive either methadone and ketamine or standard of care during their deceased donor liver transplant. * Allow researchers to follow medical care throughout inpatient stay.

Continued Access Study to Evaluate Performance of the Organ Recovery Systems _LifePort® Liver Transporter System, a Machine Perfusion System, for Liver Transplant (PILOT™_CA)

To provide continued access for the LLT system to provide additional safety data in support of the PILOT pivotal efficacy and safety trial

Immunosuppressant Withdrawal Based on Parenchymal Chimerism in the Liver Transplantation

The goal of this clinical trial is to learn whether liver parenchyma chimerism can represent a chievement of operational tolerance in liver transplantation recipients. The researchers will examine the degree of parenchyma chimerism. The participants will withdraw or minimize their immunosuppression to avoid the adverse effects of immunosuppressants.

Effect of Digital Follow-up Supported Patient Education on Immunosuppressive Medication Adherence and Quality of Life After Liver Transplantation

This randomized controlled study aimed to evaluate the effect of digital follow-up supported patient education on immunosuppressive medication adherence and quality of life in adult liver transplant recipients. Participants in both groups received standard discharge education. The intervention group additionally received structured digital follow-up messages for 12 weeks, while the control group received standard care only. Medication adherence and quality of life were assessed before and after the intervention using validated questionnaires.

Survival and Recurrence After ABO-Incompatible Living Donor Liver Transplantation for Hepatocellular Carcinoma

This retrospective cohort study aimed to evaluate long-term oncologic outcomes after ABO-incompatible living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). Patients who underwent LDLT between January 2012 and December 2023 at a single tertiary center were included. Outcomes of interest included overall survival and recurrence patterns, with a focus on differences in time to recurrence between ABO-compatible and ABO-incompatible recipients.

Study of Sleep Quality and Its Specific Determinants During the Care Pathway of a Liver Transplant Patient

In the LIVERSLEEP study, investigators provide an overview of sleep disorders among patients in a liver transplantation (LT) pathway and a description of the criteria that can influence their sleep. This is a prospective longitudinal monocentric pilot study, generating hypotheses whose main objective is to describe the evolution of sleep quality in LT patients between pre-LT evaluation (PLTE) and 6 months post-LT. The secondary objective(s) are, before LT, 2 months and 6 months after, (1) to describe the level of anxiety in our patients, (2) to estimate the proportion of patients with impaired sleep quality, and (3) to describe the characteristics of our patients' sleep. This study will cover all adult patients on the LT waiting list at the Croix Rousse Hospital transplant center for the duration of the study. The duration of the inclusion period is 18 months. For each patient, the participation period will be 1 year on average (pre-LT measurement with an average waiting time of 6 months for LT, then measurements at TH+2 months and at TH+ 6 months). The total duration of the study will be 30 months, with a theoretical start of inclusions in the third quarter of 2026. Patients likely to participate in the study will be identified by the transplant nurse coordinatoir (TNC) within the digestive surgery and LT department of the Croix-Rousse hospital in Lyon. These are all the patients seen in hepatology consultation for the announcement of a LT project. Verification of the selection or contraindication criteria will be carried out by the principal investigator. During the consultation with the hepatologist and the TNC to announce the indication for LT, the study will be presented by the physician and then detailed by the TNC (objectives, steps, submission of upcoming questionnaires). After collecting the patient's non-opposition, clinical data will be collected (weight, height, BMI, sex, age, indication, MELD score, and presence or absence of hepatic encephalopathy). Given the emotional burden of this consultation, no questionnaire will be submitted to the patient at this stage. During the PLTE, then 2 months and 6 months after LT, 5 questionnaires will need to be completed by the patient (evaluation of sleep quality, anxiety, chronotype, physical activity, and pain). The TNC also collects the presence of psychotropic treatments that can influence sleep. A sleep schedule will be sent to the patient with their appointment for the PLTE and to be completed before hospitalization. This diary will be retrieved during the PLTE by the TNC. The presence or absence of psychotropic treatment will also be recorded. Two and six months after the LT, during follow-up visits in ambulatory care, conventional hospitals, or consultations, the patient responds again to these five questionnaires on a tablet, and the TNC also collects the presence of psychotropic treatment. Finally, at a distance from the LT (2 months later), the TNC collects the duration of the patient's transplant wait (from the date of activation on the waiting list to the LT date), the number of examinations performed during the PLTE, and post-LT complications (return to the operating room, stent-like endovascular treatment, drain adhered to the skin), the duration of the PLTE (date of the first PLTE examination on the date of activation on the waiting list) and the immediate post-LT hospitalization period (in days). A comparative analysis will be conducted between patients whose sleep quality is altered and those for whom it is maintained, with some factors of interest related to the patient's clinic and care pathway. The results will serve as a basis for the implementation of a relevant intervention aimed at treating and reducing sleep disorders in our patients.

External Oblique Intercostal Plane Block for Liver Transplantation Recipient

Postoperative pain management is one of the key factors in improving rehabilitation and accelerating recovery. The external oblique intercostal plane block can be used to provide abdominal wall analgesia for effective pain control in abdominal surgery. The aim of this study is to investigate the postoperative analgesic efficacy of the external oblique intercostal plane block in liver transplant recipients. The investigators will compare a group receiving the external oblique intercostal plane block with a control group to determine whether this block provides effective postoperative analgesia in liver transplant recipients.

Rectus-Intercostal Fascial Plane Block for Liver Transplantation Donors

Postoperative pain control plays a crucial role in enhancing recovery and improving early mobilization in living liver donors. The rectus-intercostal fascial plane (RIFP) block is a novel ultrasound-guided regional anesthesia technique that provides anterior abdominal wall analgesia by targeting the intercostal nerves between the rectus abdominis and intercostal muscle fascia. This prospective, randomized controlled clinical study aims to evaluate the postoperative analgesic efficacy and opioid-sparing effects of the RIFP block compared with standard intravenous analgesia in living liver donors undergoing donor hepatectomy. Participants will be randomly assigned to two groups: Group 1 (RIFP Block): Patients receiving an ultrasound-guided rectus-intercostal fascial plane block using 20 mL of 0.25% bupivacaine at the end of surgery, in addition to standard IV PCA (morphine). Group 2 (Control): Patients receiving only standard IV PCA (morphine) without regional block.

Effect of Preoperative CIMT on Hemodynamics During Liver Transplantation

Candidates for liver transplantation (CT) carry an increased risk of cardiovascular disease (CVD) due to underlying end-stage liver disease (ESHD) and immunosuppressive drugs used post-transplantation. CVD is a significant cause of long-term mortality after CT \[1\] \[2\]. Carotid Intima-Media Thickness (CIMT), a subclinical marker of atherosclerosis in the preoperative period, is a non-invasive method used to predict future CVD risk \[3\]. High CIMT indicates atherosclerosis and decreased arterial compliance. This can compromise organ perfusion and increase the risk of postoperative complications by increasing intraoperative blood pressure variability (BPV) during anesthesia induction and surgical stress in major surgeries such as CT. Studies investigating whether CIMT is an independent risk factor for perioperative hemodynamic instability in CT patients are limited. The aim of our study is to investigate the effect of CIMT values on intraoperative hemodynamic parameters. Secondary objectives are to determine the association of CIMT with the incidence of hypotension, vasopressor requirement, postoperative acute renal injury (ARI), and major cardiac adverse events (MCAE) after anesthesia induction. Theoretical Benefit: To make a significant contribution to the literature on the relationship between atherosclerosis and anesthesia management by determining whether CIMT is an independent predictor of perioperative hemodynamic instability in chemotherapy patients. Practical Benefit: To ensure the inclusion of CIMT measurement in the anesthesia risk assessment of chemotherapy candidates. Identifying patients with high CIMT will guide the implementation of more aggressive and targeted hemodynamic management strategies (e.g., more frequent invasive monitoring, proactive vasopressor use) during anesthesia induction and maintenance.

ADDICTOlogical Intervention in LIVEr Transplantation Recipients

Transplantation for end-stage-liver disease (ESLD) in the context of Alcohol-Associated Liver Disease (AALD) has been increasing and represents the main indication for Liver Transplantation (LT) in the world. Alcohol Use Disorder (AUD) is considered a brain chronic disease and requires a transdisciplinary approach that includes medical treatment and behavioral interventions. In the context of LT, alcohol relapse occurs in 26 % up to 50% of LT recipients. Among Liver transplant recipients for AALD, severe alcoholic relapse (defined as more than 3 alcoholic drinks per day for women and 4/day for men) after LT leads to impaired longterm survival due to recurrent alcoholic cirrhosis (RAC), cardiovascular events and de novo cancer. Several strategies have been developed to prevent alcohol relapse. After LT, integrating an addiction team into the LT program has been advocated by the latest guidelines in Europe and the United States, in order to bring the management of alcohol-use disorder (AUD) in transplantation units, through the association of psychosocial and pharmacological interventions previously reported in AALD. However, those guidelines were based on descriptive studies, and the effect of this management needs to be confirmed through a randomized, controlled, multicenter study, involving centers that still do not include an addiction team in their LT programs. This study will therefore assess prospectively and comparatively the impact of an addiction intervention after LT on return to alcohol use rates. We hypothesize that standardized targeted addiction monitoring of Liver Transplant recipients decreases the rates of alcohol relapse two years post-liver transplantation.

Influence of Human Albumin Supplementation on Kidney Dysfunction After Liver Transplantation

To verify whether albumin administration to achieve serum concentration above 30g/L (treated group) and its maintenance within plasmatic physiologic range (above 30 g/L) for five days diminishes rate of AKI at Day 7 after liver transplantation as compared to restrained albumin administration (when serum concentration is at 20 g/L or below (control)).

Secretin in Ex-situ Liver Perfusion

The main objective is to assess whether the use of human synthetic secretin in a clinical (COR-)NMP procedure can restore physiological HCO3- content of the bile during ex-situ NMP.

Restrictive Fluid Management In Liver Transplantation (REFIL) - Pilot

Hypothesis: A Canadian multicentre clinical trial is feasible. Study Design: Multicenter internal pilot parallel arm randomized controlled trial. Study population: Patients with end-stage liver disease (ESLD) undergoing a liver transplantation, not meeting any exclusion criteria. Primary feasibility endpoint: An overall recruitment rate ≥ 4 patients/month across all four participating sites. Secondary feasibility endpoints: A protocol adherence \> 90%, a 30-day (or hospital discharge) and 6-month outcome measurement \> 90%, and a mean difference in total intraoperative volume received (crystalloids and colloids combined) \> 1000 ml between groups. Study intervention: Low splanchnic blood volume restrictive fluid management strategy (intervention). A phlebotomy, performed prior to dissection and transfused back after graft reperfusion, combined with a hemodynamic goal-directed restrictive fluid management strategy. Optimized cardiac-output liberal fluid management strategy (control) A hemodynamic goal-directed liberal fluid management strategy that optimizes cardiac output throughout surgery.

Effect of Discarding Initial Reperfusion Blood on Hemodynamics, Liver Function, and 30-Day Outcomes in Liver Transplantation

Hepatic reperfusion during liver transplantation remains a critical phase associated with significant hemodynamic and systemic disturbances, despite advances in surgical and anesthetic management. This phase is characterized by the release of acidotic, hypothermic, and hyperkalemic blood containing metabolic byproducts and inflammatory mediators resulting from ischemia-reperfusion injury. Clinically, reperfusion is associated with hemodynamic instability, including reductions in cardiac output and arterial pressure, as well as cardiac dysfunction and arrhythmias, often requiring pharmacologic support. These alterations may affect not only immediate intraoperative stability but also short- and long-term outcomes for both the patient and the graft. The abrupt restoration of blood flow to the transplanted liver leads to the systemic release of accumulated metabolites, reactive oxygen species, and inflammatory mediators, contributing to a systemic inflammatory response that may impact distant organs, including the kidneys and heart. Several revascularization strategies have been investigated to mitigate reperfusion-related injury: initial reperfusion via the portal vein, initial reperfusion through the hepatic artery, and simultaneous reperfusion through the portal vein and hepatic artery. A less frequently used and insufficiently studied strategy, not routinely or systematically implemented, involves diverting the initial reperfusion blood from the graft to the surgical field, followed by the restoration of hepatic blood outflow to the systemic circulation. This study hypothesizes that discarding the initial reperfusion blood via the infrahepatic vena cava will attenuate early hemodynamic, metabolic, and inflammatory changes and reduce postoperative complications compared to conventional reperfusion techniques.