Clinical Research Directory

Daridorexant for Sleep Disturbance in Adults With Liver Cirrhosis

This study will evaluate the efficacy and safety of daridorexant, a dual orexin receptor antagonist, in adults with liver cirrhosis and sleep disturbance, including participants with or without covert hepatic encephalopathy. Sleep disturbance is common in people with liver cirrhosis and may affect quality of life and cognitive function. Participants will be randomly assigned to receive either daridorexant or a matching placebo for 30 days. Neither participants nor study investigators will know which treatment is assigned during the study, except when unblinding is medically necessary. Sleep and cognitive function will be assessed during the study using sleep monitoring, the Psychometric Hepatic Encephalopathy Score (PHES), and the Stroop EncephalApp, together with other clinical and laboratory assessments. The main purpose of the study is to determine whether daridorexant improves sleep efficiency compared with placebo after 30 days. The study will also evaluate changes in sleep quality, sleep structure, cognitive function, the occurrence or improvement of covert hepatic encephalopathy, and the safety of daridorexant. A total of 180 participants are planned to be enrolled at multiple participating hospitals and will be randomly assigned in a 1:1 ratio to daridorexant or placebo.

Within-Session Repeatability of EUS-Guided Portal Pressure Gradient Measurement

This prospective multicentre observational reliability study will determine how much a repeated endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) measurement differs from the first measurement in the same patient during the same procedural session. Each participant will undergo two complete EUS-PPG measurement sets using an identical 22-gauge measurement setup. The study will quantify within-session repeatability when the same expert performs both sets and inter-operator reproducibility when different operators perform the sets.

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.

Equivalence of Electronic vs Paper-based PHES in Diagnosing Hepatic Encephalopathy

The goal of this clinical trial is to learn if an electronic version of the Psychometric Hepatic Encephalopathy Score (PHES) works as well as the standard paper version to diagnose minimal hepatic encephalopathy (MHE) in adults with liver cirrhosis. The main questions it aims to answer are: Do the total scores of the electronic and paper tests match for the same patient? Do both tests classify patients as having MHE or not in the same way? Researchers will compare the electronic PHES to the paper PHES to see if they produce equivalent results. Participants will: Be assigned by chance to one of two groups. Group A will take the paper test first, then the electronic test the next day. Group B will take the electronic test first, then the paper test the next day. Complete two cognitive tests (one paper-based and one electronic) on two separate days. Provide information about their medical history and complete routine blood tests as part of their standard care.

A Study to Test Whether BI 3802876 is Tolerated in People With Compensated Liver Cirrhosis Due to Metabolic Dysfunction- Associated Steatohepatitis (MASH)

This study is open to adults with a type of confirmed liver condition called compensated cirrhosis due to Metabolic Dysfunction-Associated Steatohepatitis (MASH). The purpose of this study is to find out how well a study medicine called BI 3802876 is tolerated in people with this condition. The study looks at how different doses of BI 3802876 are handled by the body. BI 3802876 is being developed to improve liver health in people living with this liver condition. Participants are put in 3 different dose groups randomly, which means by chance. Participants within a group get BI 3802876 or placebo. Placebo looks like BI 3802876 but does not contain any medicine. Participants have more than twice the chance of receiving BI 3802876 than placebo. The study medicine is given as an infusion into a vein. Participants are in the study for about half a year. During this time, they visit the study site 12 times. At 2 visits, participants get the study medicine. Doctors collect information on any health problems and take blood samples to check how BI 3802876 is handled by the body. They compare results between the groups.

Value of [68Ga]Ga-PSMA-11 PET/MRI in the Assessment of Liver Cirrhosis

A total of fifty-five (55) patients with liver cirrhosis will be enrolled in this study to produce and validate dedicated Ga-PSMA-PET/MRI acquisition protocols. The specific hypotheses include: * Ga-PSMA PET/MRI may allow robust and reproducible noninvasive in vivo quantitation of hepatic macro and microhemodynamics in cirrhotic patients * Dedicated simultaneously acquired DWI sequences might quantitate liver fibrosis and improve hemodynamic quantitation. * Ga-PSMA PET/MRI may allow noninvasive and reproducible quantitation of portal venous hypertension and predict its evolution, as well as response to treatments * Ga-PSMA PET/MRI may improve noninvasive and reproducible qualitative and quantitative assessment of liver function, structure, nodules and predict evolution of cirrhosis

AGRA Before and After Liver Transplantation

The immune system is impaired in liver cirrhotic patients, which is associated with a high risk for bacterial infections and worse outcome. A novel biomarker, acellular growth retardation ability (AGRA), can predict the development of severe infections in patients with liver cirrhosis and therefore identify patients at risk. It is still unclear, how this biomarker develops after liver transplantation and how valid its predictions are for post-operative infections. Therefore, AGRA will be measured before and after liver transplantation and predictive merit of AGRA for post-transplant infections will be tested.

Microbiome and Sarcopenia in Patients With Liver Cirrhosis

Protein-energy malnutrition (PEM) occurs in 65-90% of patients with liver cirrhosis. Severity of malnutrition correlates with progression of liver disease and leads to sarcopenia in 30-70% of cirrhotic patients. Malnutrition and sarcopenia are associated with an increased risk of complications and mortality. In cirrhosis the gut microbiome is altered leading to increased gut permeability, bacterial translocation and inflammation. Since the microbiome is involved in nutrient uptake and metabolism, it is hypothesized that microbiome alterations contribute to sarcopenia. A prospective controlled cohort study to investigate the interrelation of microbiome changes and sarcopenia in cirrhosis will be conducted. Furthermore the effect of nutritional interventions on the microbiome in cirrhosis will be studied. From this study information on how the gut microbiome composition and sarcopenia are associated in cirrhosis and if modulation of the gut microbiome by nutritional interventions is feasible will be collected.

Periinterventional Coagulation Management of Patients Undergoing a TIPS

Assess whether a pre-interventional thrombelastography guided algorithm for assessing and correction of coagulation status in cirrhotic patients is safe and effective

Real-world Elecsys® GAAD Implementation and Validation to Improve Surveillance and Early Detection of HCC

Patients with liver cirrhosis are at high risk of developing hepatocellular carcinoma (HCC) which implies significant mortality. At present current surveillance methods detect hepatocellular carcinomas at a late stage resulting in few treatment options for patients and, in the majority of cases, premature death. The goal of this study is to implement Elecsys® GAAD in real-world hepatocellular carcinoma surveillance for those with liver cirrhosis. The main questions it aims to answer are: * Does the introduction of the Elecsys® GAAD algorithm to the surveillance pathway increase early detection of HCC? * Does the introduction of the Elecsys® GAAD algorithm to the surveillance pathway reduce false positive tests and unnecessary confirmatory investigations? * Does the new surveillance pathway improve adherence? Researchers will compare Elecsys® GAAD with standard of care tests to see if it results in earlier detection of hepatocellular carcinoma and will explore potential improvements to the surveillance pathway.

HepHospital: A Pilot Trial of a Hepatology Home Hospital Intervention for Patients With Advanced Liver Disease

This research study is evaluating a program that entails a healthcare at home intervention for people with advanced liver disease.

Lifestyle, Dietary Patterns, and Cardiometabolic Risk in Metabolic Dysfunction-Associated Steatotic Liver Disease Among People Living With HIV

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is an increasingly recognized comorbidity in people living with human immunodeficiency virus (HIV). Chronic low-grade inflammation, altered lipid metabolism, and certain antiretroviral therapy (ART) regimens may heighten the vulnerability of people living with HIV (PLWH) to liver fat accumulation, progressive liver fibrosis, and cardiometabolic complications. The primary purpose of this observational case-control study is to determine the prevalence, clinical characteristics, and laboratory findings of MASLD and hepatic fibrosis among PLWH compared with matched HIV-negative individuals. The study also aims to evaluate dietary quality, lifestyle habits, and cardiovascular risk profiles in both groups, and to determine whether adherence to a healthy lifestyle protects against significant liver disease. Adult participants (aged 18 years and older) attending the Department of Tropical Medicine and Gastroenterology at Assiut University Hospitals will be enrolled into two groups: people living with HIV and HIV-negative individuals matched by age, sex, and degree of liver steatosis. All participants will complete the following non-invasive evaluations: * Hepatic Assessment: Abdominal ultrasound and transient elastography (FibroScan) to detect fatty liver and quantify liver stiffness, alongside non-invasive scoring systems (FIB-4 score and NAFLD Fibrosis Score). * Laboratory Investigations: Fasting blood tests including liver function tests, lipid profiles, glycemic status (HbA1c), kidney function, complete blood count, and immune markers (CD4+ T-cell count and CD4/CD8 ratio). * Physical and Body Measurements: Measurement of body mass index (BMI), waist circumference, and mid-arm muscle circumference (MAMC). * Dietary and Lifestyle Questionnaires: Validated assessment tools including the Food Frequency Questionnaire (FFQ), Short Healthy Eating Index (sHEI), and Healthy Lifestyle Questionnaire to quantify nutritional quality, physical activity, and daily lifestyle habits. * Cardiometabolic Risk Calculation: Calculation of predicted cardiovascular risk using the American Heart Association PREVENT risk score. Findings from this study are intended to clarify the role of dietary quality and lifestyle factors in liver and metabolic health among people living with HIV, potentially informing proactive screening and management strategies.

A Phase 2 Study of Foscenvivint in Liver Cirrhosis Patients Caused by HIV/HCV Co-infection With Hemophilia

This is a phase 2 study to evaluate the efficacy and safety of foscenvivint in patients with liver cirrhosis resulting from HIV/HCV co-infection in the setting of hemophilia.

Electronic PHES vs Paper-based PHES for Hepatic Encephalopathy

This is a prospective, multicenter, randomized crossover diagnostic accuracy study. A total of 80 patients with liver cirrhosis will be enrolled and randomly assigned to two sequence groups at a 1:1 ratio. Participants in Sequence A will complete the paper-based Psychometric Hepatic Encephalopathy Score (PHES) on Day 1 and the electronic PHES on Day 2; participants in Sequence B will receive the tests in reverse order. All tests will be performed at the same time of day with a 1-day washout interval to minimize carryover effect. The primary objective is to verify the equivalence of total scores between electronic and paper-based PHES. Secondary objectives include evaluating the consistency of MHE classification and individual subtest scores, and analyzing the effects of test sequence and time period on results. This study aims to provide evidence for clinical promotion of the electronic PHES tool.

A Prospective Cohort Study on the Epidemiological Investigation, Diagnosis, and Treatment of Hepatic Encephalopathy

Purpose Hepatic encephalopathy (HE) is a serious complication of liver cirrhosis that can cause memory loss, slow reaction, and even coma. In China, large-scale epidemiological data on HE are lacking, early diagnosis remains difficult, and treatment needs improvement. This study aims to investigate the prevalence of HE in Chinese liver disease patients and to explore better diagnostic methods and treatment strategies. Design This is a prospective, multicenter cohort study led by Jiangsu Province Hospital, in collaboration with 7 other hospitals in Jiangsu Province. Between April 2026 and December 2029, the study plans to enroll over 700 patients with liver cirrhosis and 120 healthy volunteers. What participants will do Participants will use a WeChat mini-program to perform simple cognitive tests (e.g., reaction speed, attention) regularly. They will be followed up at month 1, 3, 6 after enrollment, and then every six months. The research team will collect routine laboratory results, medication records, and quality-of-life data. Benefits and risks Participants will receive closer health monitoring, which may help detect changes early. The study involves no additional drugs or invasive procedures, so risks are very low. All personal information will be kept strictly confidential and used only for medical research. Voluntary participation Participation is completely voluntary, and participants can withdraw at any time without affecting their routine medical care.

Zibotentan and Dapagliflozin Combination, EvAluated in Liver Cirrhosis (ZEAL Study)

This is a two part Phase IIa/b multicentre, randomised, double-blind, placebo-controlled, parallel group dose-ranging study to assess the efficacy, safety, and tolerability of the combination of zibotentan and dapagliflozin, and dapagliflozin monotherapy versus placebo in participants with cirrhosis with features of portal hypertension.

National Liver Cancer Screening Trial

The National Liver Cancer Screening Trial is an adaptive randomized phase IV Trial comparing ultrasound-based versus biomarker-based screening in 5500 patients with cirrhosis from any etiology or patients with chronic hepatitis B infection. Eligible patients will be randomized in a 1:1 fashion to Arm A using semi-annual ultrasound and AFP-based screening or Arm B using semi-annual screening using GALAD alone. Randomization will be stratified by sex, enrolling site, Child Pugh class (A vs. B), and HCC etiology (viral vs. non-viral). Patients will be recruited from 15 sites (mix of tertiary care and large community health systems) over a 3-year period, and the primary endpoint of the phase IV trial, reduction in late-stage HCC, will be assessed after 5.5 years.

Safety and Adequacy of Trans-jugular Liver Biopsy in Patients With Liver Disease: SAFE-TJLB Study

Liver biopsy is considered the gold standard for the evaluation of acute and chronic liver disorders. Liver biopsy provides information regarding diagnosis, disease progression, and response to therapy in patients with chronic liver diseases. Trans-jugular liver biopsy (TJLB) consists of obtaining liver tissue through a rigid cannula introduced into one of the hepatic veins typically using jugular venous access. This approach reduces the risk of hemorrhage after biopsy because the bleeding resulting from the biopsy needle will drain into the hepatic veins. In the past, the specimens obtained by a transjugular approach were considered suboptimal compared with the samples obtained with percutaneous needles because they were smaller and more fragmented. TJLB was initially indicated for patients who had a contraindication to percutaneous biopsy such as those with a coagulopathy or congenital clotting disorders, ascites, acute liver failure, large amount of adipose tissue, and patients after liver transplantation. The clinical role of TJLB has expanded due to the possibility of performing hemodynamic evaluation of the hepatic and portal venous systems, which provides useful information and may guide therapy in patients with portal hypertension. Lacuna in literature: There is no prospective study in India evaluating the safety and efficacy of trans-jugular liver biopsy in patients with liver disease.

A Novel Extracorporeal Liver Support Therapy In ALCF and to Evaluate the Efficacy of DIALIVE 2.0, a Liver Dialysis Device.

This study is intended to demonstrate the efficacy and safety of the DIALIVE Liver Dialysis Device when incorporated into the standard management plan for participants with A-TANGO ACLF grade 2-4. A total of 72 evaluable participants, aged 18-70, will be enrolled in up to 12 clinical centres in the United Kingdom. Participants must have a history of liver cirrhosis and a deterioration within four weeks due to a precipitating event, leading to A-TANGO ACLF grade 2-4. Multicenter, individually randomised, controlled, open-label, parallel group trial using double-arm design. The control group will receive SoC for participants with ACLF. The DIALIVE 2.0 treatment group will receive SoC with the addition of up to 7 (seven) daily DIALIVE 2.0 treatment sessions within the 10-day treatment window. Seventy-two participants with ACLF (60% A-TANGO ACLF grade 2 at randomisation, and 40% A-TANGO ACLF grade 3 \& 4 at randomisation) will be randomised 1:1 to receive either SoC or SoC + DIALIVE 2.0. This allows for 5% loss due to drop-out, and 5% censoring due to liver transplantation within 28 days. All randomised participants will be included in the intention to treat (ITT) analysis while all participants that receive at least one treatment cycle will be used for the safety population. For each participant, the study duration will be up to 105 days (screening: 5 days; treatment up to 10 days; follow up 90 days). The total study duration is estimated to be approximately 18 months from screening of first participant until study completion of the last participant.

Using Autologous Bone Marrow Cells With Wharton Gel Exosomes to Stimulate Hepatic Cell Repair in Liver Cirrhosis

the study includes patients with liver cirrhosis irrespective of the stage excluding people with active tumor or other major health issue endangering life, the protocol includes the use of autologous bone marrow derived mononuclear cells harvested from the same patient under local anesthesia ,followed by cell concentration and viability testing , then final product is combined with small volume of 2 cc of Wharton gel exosomes 20 billion per to be administered intravenously.

Effect of Handgrip Strength on Portal Vein Hemodynamics in Patients With Liver Cirrhosis

1. Background Handgrip strength , a core indicator of muscle function, has been confirmed to be significantly associated with the clinical prognosis of patients with liver cirrhosis. However, no studies have explored its correlation with portal venous hemodynamics. 2. Objective The purpose of the study is to examine the effects of Handgrip strength on portal vein and left gastric vein pressure, blood flow velocity and direction in patients with liver cirrhosis, as well as its hemodynamic impact on gastroesophageal varices. 3. Method Study Design: Interventional study. Detection Timing: Hemodynamic indices were measured simultaneously after patients achieved their maximum handgrip strength. Participants were divided into three groups based on the assessment methods. Group 1 (Portal Pressure Measurement Group): Before the placement of TIPS, the pressures of the portal vein and left gastric vein were measured, both before and after the handgrip strength test. Group 2 (Doppler Ultrasound Measurement Group): Measurements of portal flow velocity and direction were taken before and after the handgrip strength test, based on Doppler ultrasound. Group 3 (Endoscopic Ultrasound Measurement Group): Measurements of blood flow volume and direction in esophagogastric varices were conducted before and after the handgrip strength test, based on endoscopic ultrasonography. The inclusion and exclusion criteria were described. 4. Elaboration of the Research Hypothesis 4.1. Core Hypothesis The handgrip strength level in patients with liver cirrhosis is correlated with portal venous system hemodynamic indices. Specifically, enhanced handgrip strength may affect portal hypertension and the hemodynamics of varicose veins by improving systemic muscle function or circulatory status. 4.2. Speculation on potential mechanisms Association between muscle function and circulation: As a representative of systemic muscle function, increased handgrip strength may reflect an increase in cardiac output or changes in splanchnic vascular resistance, thereby influencing portal venous hemodynamics. Effects on varicose veins: Improved handgrip strength may reduce blood flow velocity or diameter of esophagogastric varices by decreasing splanchnic congestion or regulating local vascular tension, thus lowering the risk of variceal rupture and bleeding. Role of compensatory mechanisms: Muscle wasting is common in decompensated cirrhosis. Patients with higher handgrip strength may have better compensatory capacity, and the degree of hemodynamic disorder in their portal venous system may be less severe. Conclusion This study uses a multi-method grouping design to first explore the association between handgrip strength and portal venous hemodynamics in cirrhotic patients. The hypothesis is based on the potential regulatory role of muscle function in the circulatory system, which is expected to provide a new non-invasive indicator for clinical assessment of portal hypertension risk.

A Novel COMBinATorial Therapy With Albumin and Enoxaparin in Patients With Decompensated Cirrhosis at High-risk of Poor Outcome (COMBAT Trial).

The goal of this clinical trial is to determine primarily whether a combinatorial therapy based on the administration of human albumin and enoxaparin is safe and effective in patients with decompensated cirrhosis discharged from the hospital. The main questions it aims to answer are: * Is this combinatorial therapy safe and tolerable? * Is this combinatorial therapy effective? * does this combinatorial therapy cost more or less than standard medical therapy? Participants will attend to study visits in which several test will be performed to asses disease evolution while they are taking study medication. Researchers will compare experimental group treated with combinatorial therapy plus standard treatment with control group treated with standard treatment to see if there are differences in the responses to the questions raised above.

Validation of New Prognostic Biomarkers in Patients With Decompensated Cirrhosis

The study aims to test the effectiveness of new biomarkers (measurable molecules in our body) in predicting the health outcome of patients with liver cirrhosis discharged from the hospital after a serious complication of the disease

Effect of Laparoscopic Hepatectomy Combined With Splenectomy on Hepatic Functional Reserve and Immune Function

Splenectomy may relieve hypersplenism, reverse liver fibrosis, improve hepatic functional reserve, and reshape the systemic antitumor immune milieu by removing the source of negative immunomodulation. This prospective cohort study aims to enroll patients undergoing laparoscopic hepatectomy combined with splenectomy for small hepatocellular carcinoma（HCC） with a preoperative platelet count \<80×10\^9/L. The study will evaluate the dynamic changes in hepatic functional reserve, immune function, and risk of HCC recurrence through five post-surgical time points（3, 6, 12, 18, and 24 months after surgery）. The endpoints include hepatic functional reserve（ICG-R15, Child-Pugh score, ALBI score, etc.）, immune function indicators（peripheral blood lymphocyte subsets: CD4\^+ T cells, CD8\^+ T cells, regulatory T cells, NK cells, etc., and serum cytokine profiles）, and HCC recurrence rate within 2 years after surgery（confirmed by imaging）. This trial will provide evidence to optimize surgical strategies for patients with small HCC complicated with hypersplenism.