Clinical Research Directory

Austrian PBC Registry

The goal of this registry is to better understand how primary biliary cholangitis develops over time, including the role of disease-related biomarkers, complications of the disease, and symptom burden. Patients with primary biliary cholangitis treated at participating centres in Austria will be invited to take part in this prospective registry. Participation in an associated biobank is optional. Clinical and laboratory data will be collected, and patients will be followed regularly through scheduled clinic visits. In addition, biological samples (serum, plasma, and, if available, liver tissue) may be collected and stored in the biobank for future research.

Long-term Efficacy and Safety of LSD Versus TIPS for Cirrhotic Portal Hypertension Bleeding and Hypersplenism

This study aims to compare two treatments for cirrhotic portal hypertension with acute esophagogastric variceal bleeding and hypersplenism: laparoscopic splenectomy and azygoportal disconnection (LSD) and transjugular intrahepatic portosystemic shunt (TIPS). It is a single-center, prospective trial. The primary outcome is the incidence of post-procedure hepatic encephalopathy. Secondary outcomes include changes in hepatic venous pressure gradient, portal and hepatic artery hemodynamics, liver function, renal function, complete blood count, immune function, hepatic reserve capacity, serological markers of liver fibrosis, re-bleeding rate, hepatocellular carcinoma incidence, recompensation incidence, overall survival, and bleeding-free survival. The study will provide high-level evidence for optimal treatment selection in this patient population.

Sonazoid CEUS for Early HCC Surveillance

This study is a multicenter, prospective study. In this study, enrolled subjects are cirrhotic patients of any etiology. The US and Sonazoid CEUS monitoring strategy was performed for cirrhotic patients: US and AFP joint with Sonazoid CEUS every 4 to 6 months, and combined CECT/CEMRI every 12 months.

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.

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.

Ultrasound Prediction of Esophageal Variceal Bleeding Risk

This prospective observational study aims to evaluate the accuracy of using routine abdominal ultrasound to predict the risk of esophageal variceal bleeding in adult patients with liver cirrhosis. Esophageal variceal bleeding is a serious complication of chronic liver disease. While upper gastrointestinal endoscopy is the current standard for diagnosing and grading these varices, it is an invasive procedure. In this study, researchers will use ultrasound to measure the patient's spleen size and portal vein diameter. These non-invasive measurements will then be compared to the results of a standard upper endoscopy performed within 48 to 72 hours. The goal is to determine if these simple ultrasound measurements can reliably predict the presence, grade, and bleeding risk of esophageal varices, which could potentially reduce the need for routine invasive endoscopic screenings in the future.

Clinical Application of Simcyp-Guided Warfarin Initiation Doses in Cirrhotic Patients With Portal Vein Thrombosis

This was a prospective, open-label, pilot interventional clinical study conducted on Egyptian patients with liver cirrhosis complicated by portal vein thrombosis (PVT) who were indicated for anticoagulation therapy. The study aimed to evaluate the clinical applicability of Simcyp®-guided warfarin initiation doses according to Child-Pugh class, focusing on the time required to achieve a therapeutic INR and the safety of anticoagulation during the initiation phase.

The Diagnostic Value of Subharmonic Imaging Technology Combined With Liver Stiffness and Platelet Count for High-risk Esophageal and Gastric Varices in Patients With Liver Cirrhosis

To evaluate the diagnostic value of the combined model of subharmonic-assisted pressure estimation (SHAPE), liver stiffness (LSM), and platelet count (PLT) for high-risk esophageal and gastric varices (HRV)

Freiburg TIPS Registry

Patients with clinically significant portal hypertension allocated to implantation of a transjugular intrahepatic portosystemic shunt (TIPS) at the Department of Medicine II of the University Medical Center Freiburg, Germany will be offered to participate in this prospective observational trial. Clinical and laboratory as well as outcome parameters will be assessed before and within the first 12 months after TIPS implantation following a regular follow-up schedule with clinical visits at the University Medical Center Freiburg. During follow-up visits, serum/plasma samples and peripheral blood mononuclear cells (PBMC) are collected and stored in a associated biobank.

Portal Vein Thrombosis in Liver Cirrhosis: Clinical Characteristics, Radiological Patterns, and Predictors

Portal vein thrombosis (PVT) is a common complication in patients with liver cirrhosis and is associated with increased morbidity due to worsening portal hypertension and hepatic decompensation. The clinical presentation and radiological patterns of PVT vary widely, and the factors predicting its development remain incompletely understood. This observational study will include adult patients (≥18 years) with established liver cirrhosis who are admitted to the Department of Gastroenterology and Tropical Medicine, Al-Rajhi Liver Hospital, Assiut University. Eligible participants will undergo routine screening for PVT using Doppler ultrasonography, with confirmation by contrast-enhanced computed tomography when indicated. The study aims to evaluate the clinical characteristics, laboratory parameters, and radiological features of PVT. Cases of PVT will be classified according to extent (partial or complete) and anatomical location (main portal vein, right branch, left branch, or combined involvement). Clinical and laboratory data will be analyzed to identify potential predictors associated with the development and severity of PVT. The findings of this study are expected to improve understanding of the risk factors and radiological patterns of PVT in cirrhotic patients, contributing to better risk stratification and clinical management.

Early TIPS in Patients With Liver Cirrhosis and Ascites

The aim of this clinical trial is to compare the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) implantation with standard treatment (diuretic medications, and if necessary, paracenteses) in patients with liver cirrhosis and development of ascites as the first decompensating event. By creating a shunt between the liver vein and the portal vein, blood is diverted from the portal vein directly into the hepatic vein, which results in a reduction of pressure in the portal vein so that development of ascites is reduced.

A Phase 2 Trial of Foscenvivint in Liver Cirrhosis Patients Caused by HIV/HCV Co-infection With Hemophilia (OP-724-H201)

This is a phase 2 trial of foscenvivint in liver cirrhosis patients caused by HIV/HCV co-infection with hemophilia to evaluate the efficacy, safety and pharmacokinetics.

Endoscopic Shunts Embolization for Refractory Hepatic Encephalopathy

The goal of this clinical trial is to learn if endoscopic ultrasound guided (EUS guided) spontaneous porto-systemic shunt (SPSS) embolization works to treat refractory hepatic encephalopathy in adults. It will also learn about the safety of EUS guided embolization. The main questions it aims to answer are: 1. Does EUS guided embolization maintain an acceptable safety profile? 2. Does EUS guided embolization of large SPSS result in significant clinical improvement in patients with refractory hepatic encephalopathy? Participants will: 1. Receive EUS guided embolization or medical management. 2. Receive follow-up EUS procedures one month after embolization for assessment of the shunt patency and development of varices (embolization group). 3. Receive follow-up every week for 4 weeks to assess degree of worst episode of hepatic encephalopathy via West Haven criteria.

Use of Gender, Age, Alfa-fetoprotein (AFP), and Des-gamma-carboxyprothrombin (PIVKA-II) or GAAD Score in Addition to Ultrasound for Surveillance of People At-risk for Developing Hepatocellular Carcinoma in Asia in Order to Detect Early Liver Cancer

HCC surveillance is currently limited by underutilization and the suboptimal performance of AFP. This prospective, single-arm study investigates whether the GAAD score (Gender, Age, AFP, and PIVKA-II) enhances HCC detection when added to standard-of-care surveillance. High-risk patients will undergo US plus GAAD score testing every six months for two years. The primary analysis compares the relative true positive rate (rTPR) and relative false positive rate (rFPR) of surveillance modalities (US, AFP, GAAD) against combined strategies (US+AFP; US+GAAD), utilizing a 2.57 GAAD cut-off. Secondary endpoints include longitudinal biomarker kinetics, early-stage HCC detection rates, and the impact on downstream imaging (CT/MRI) volume. Ultimately, this study seeks to define the role of GAAD as a surveillance adjunct and inform future clinical guidelines for biomarker-enhanced HCC screening.

Annual MRI Versus Biannual US for Surveillance of Hepatocellular Carcinoma in Liver Cirrhosis

The investigators will investigate the usefulness of biannual ultrasonography versus annual non-contrast magnetic resonance imaging for surveillance of hepatocellular carcinoma in single arm patients.

Exploration of Systemic and Portal Hemostasis in Patients Undergoing Transjugular Intrahepatic Portosystemic Shunt Placement

Portal vein thrombosis is defined as non-tumoural obstruction of the portal vein or one of its branches. Its incidence is 0.7 to 2.7 per 100,000 patient-years in the general population, and 4.6 per 100 patient-years in patients with cirrhosis. Histological modificaitions fo the portal vein wall and haemostatic changes have been described in cirrhotic patients. The contribution of these changes, both systemic and local, to the development of portal vein thrombosis is debated. One of the hypotheses put forward on the genesis of portal vein thrombosis is as follows: certain bacterial translocations from the digestive tract, promoted by portal hypertension, contribute to endothelial activation resulting in the release of von Willebrand factor and factor VIII, as well as platelet activation and the coagulation cascade, which is dysregulated by cirrhosis and underlying changes in haemostatic balance. Inflammatory phenomena and NETosis may also be involved. Studies suggest that cirrhotic patients have lesions of the glycocalyx located in the portal area, which may be involved in the development of portal vein thrombosis. Patients with cirrhosis may benefit from the placement of a transjugular intrahepatic portosystemic shunt (TIPS). During the TIPS placement procedure, blood is drawn from the internal jugular vein and the portal vein, allowing for parallel biological analyses. The assumption of this study is that haemostasis and inflammation are disrupted differently at the systemic and portal levels in cirrhotic patients.

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.

Endothelin Receptor Antagonism With Ambrisentan to Treat Hepatorenal Syndrome

Patients with advanced cirrhosis of the liver develop kidney problems occasionally. This condition is called Hepatorenal Syndrome, requires hospitalization and frequently results in death. The goal of this clinical trial is to test whether the administration of low doses of ambrisentan can help patients with Hepatorenal Syndrome and to determine if it is safe. Ambrisentan is a drug that is approved for the treatment of high blood pressure in the lungs at higher doses. This clinical trial will compare the safety and effects of ambrisentan to another drug called terlipressin, which is commonly used to treat patients with hepatorenal syndrome. The main questions the clinical trial aims to answer are: * Does ambrisentan help the kidney function of the patient? * Does ambrisentan help prevent death in patients with Hepatorenal Syndrome? * Does ambrisentan prevent Hepatorenal Syndrome from reappearing? While in the hospital, trial participants will receive either one of two doses of ambrisentan or terlipressin. If in the first 4 days, ambrisentan is not helpful, the patient may be eligible to receive terlipressin. Patients assigned to receive ambrisentan will continue taking this medication at home after leaving the hospitals and until they complete 60 days of treatment.

Pantoprazole After Prophylactic Endoscopic Variceal Treatment

Traditionally, it is considered that gastric acid delays ulcer healing, and acid suppression can reduce the risk of post-banding ulcer bleeding and promote mucosal healing at the ulcer site. A systematic review and meta-analysis performed by our team demonstrated that acid suppression significantly reduced the incidence of gastrointestinal bleeding (GIB) following prophylactic endoscopic variceal ligation (EVL), but had no significant effect on the incidence of mortality, adverse events, or length of stay. Similarly, another systematic review and meta-analysis performed by Lin et al. indicated that proton pump inhibitor (PPI) significantly reduced the incidence of GIB after therapeutic or prophylactic endoscopic variceal treatment (EVT), and the efficacy of PPI in reducing post-EVT GIB is related to the duration of PPI. However, previous studies have indicated that long-term use of PPI may increase the risk of bacterial infections and hepatic encephalopathy in patients with cirrhosis. Therefore, current guidelines suggest that PPI should be discontinued after EVT, unless the patient has a clear indication for PPI. However, the quality of evidence is poor due to the small sample sizes, predominantly retrospective designs, and inconsistencies in follow-up duration of previous studies. In current clinical practice, most physicians still prefer to use PPI routinely after EVT to prevent post-EVT GIB. Given the ongoing controversy regarding the routine use of PPI after EVT, we plan to conduct a multicenter randomized controlled trial to to explore the effect of PPI after prophylactic EVT on the incidence of short-term GIB, adverse events, and mortality in patients with cirrhosis and esophagogastric varices (EGV).

Heart Problems in Children With Chronic Liver Disease

Chronic liver disease (CLD) in children can sometimes lead to complications in other parts of the body, including the heart. The primary purpose of this observational study is to assess the presence and type of cardiac problems in children who have been diagnosed with chronic liver disease. Researchers will observe children under the age of 18 who are receiving care at the gastroenterology and hepatology unit at Assiut University Children Hospital. Participants will undergo standard medical evaluations to check both their liver and heart health. These evaluations include: * A detailed medical history and thorough physical examination * Routine blood tests to check liver function, kidney function, coagulation, and electrolytes * Abdominal imaging, such as an ultrasound, to look at the liver. * An electrocardiogram (ECG) to check the heart's electrical activity and rhythm, including measuring the QTc interval. * An echocardiogram to look at the structure of the heart and check how well its chambers and valves are functioning. The study aims to identify specific heart conditions that can be associated with severe liver disease, such as portopulmonary hypertension, cirrhotic cardiomyopathy (changes in the heart muscle's function), and electrical repolarization abnormalities. Children who already have known congenital heart disease or a history of other heart problems will not be included in the study.

Multiparametric Ultrasound for the Noninvasive Diagnosis of Porto-sinusoidal Vascular Liver Disorder

Porto-sinusoidal vascular disease (PSVD) is a rare clinical entity characterized by significant portal hypertension in the absence of cirrhosis on liver histology, which may or may not show specific alterations of the portal vein, sinusoids, or hepatic lobular architecture. Currently, diagnosis of this condition necessarily requires a liver biopsy and, despite some differences detected on imaging studies-and particularly on liver and spleen elastography-PSVD remains indistinguishable from cirrhosis using non-invasive tests. Contrast-enhanced ultrasound (CEUS) is an easy-to-perform, repeatable, and cost-effective examination that enables real-time assessment of parenchymal or focal liver lesion perfusion. Moreover, the application of dynamic contrast-enhanced ultrasound (DCE-US-i.e., contrast-enhanced ultrasound followed by quantitative perfusion analysis using dedicated software, such as the VueBox Software that will be used in this study) allows integration of CEUS qualitative assessment with quantitative evaluation of tissue perfusion through analysis of time-intensity curves generated during contrast transit. From this analysis, several perfusion-related parameters can be derived (for example, peak enhancement, time to peak, or area under the curve), which have already proven useful in improving differential diagnosis of focal liver lesions and in predicting treatment response and systemic therapy outcomes. To date, the use of DCE-US for the diagnosis of PSVD has not yet been described; however, based on the underlying histological alterations associated with this disease, it is reasonable to hypothesize that parameters obtained with this technique in the liver parenchyma of patients with PSVD may differ from those measured in patients with liver cirrhosis. The aim of the present project is to apply DCE-US in patients with PSVD and in patients with cirrhosis to evaluate potential significant differences in perfusion parameters, and to assess the feasibility of a non-invasive differential diagnosis between the two conditions using this technique in combination with elastography and bidimensional ultrasound data to develop a multiparametric diagnostic score.

Utilizing of Physiological Parameters Predict the Prognosis of Cirrhotic Patients With Gastrointestinal Bleeding

Can physiological indicators such as quick Sequential Organ Failure Assessment , Shock Index, and its derived indicators such as Modified Shock Index , Age Shock Index and Respiratory Adjusted Shock Index accurately predict the prognosis of cirrhosis patients with gastrointestinal bleeding? To explore the improvement of emergency and critical care patient management.

Safety Evaluation of MSC-based Therapy for Liver Cihcrosis Treatment

This study Phase 1 clinical trial aimed to evaluate the safety and preliminary efficacy of intravenously administered extracellular vesicles derived from umbilical cord mesenchymal stem cells (UC-MSC-EVs; VinEV-3) in patients with liver cirrhosis. The trial uses a rolling six dose-escalation design, enrolling up to 12 adult patients (18-75 years) with Child-Pugh scores of 7-12. The results of this study are expected to provide initial clinical evidence supporting the safety and potential therapeutic role of UC-MSC-EVs as a novel cell-free treatment approach for liver cirrhosis.

Fiber-Optic Navigation During TIPS Creation: A Prospective Pilot Study

Transjugular intrahepatic portosystemic shunt (TIPS) creation is an established minimally invasive treatment for complications of portal hypertension such as refractory ascites and variceal bleeding. A technically challenging step of the procedure is the puncture of the portal vein from the hepatic vein, which is usually performed under fluoroscopic guidance and may require multiple puncture attempts. This prospective pilot study evaluates the use of fiber-optic navigation technology during TIPS creation. The system allows real-time three-dimensional visualization of guidewires and catheters and may improve spatial orientation during the procedure. Approximately 30 patients with a clinical indication for TIPS placement will be included. The study will assess procedural parameters such as the number of puncture attempts, fluoroscopy time, radiation exposure, procedure duration, technical success, and complications. The results may help to improve procedural efficiency and radiation safety during TIPS interventions.