Liver Disease

Researchers are studying chronic liver diseases and tumors, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC). These conditions can be caused by viral infections like hepatitis B, C, and D or lifestyle factors such as overeating and lack of exercise. The goal is to develop better understanding and new treatments by analyzing liver tissues and tumors at the single-cell level to identify therapeutic targets and improve patient outcomes. The study involves creating patient-derived preclinical models, such as spheroid cultures and mouse xenograft models, to test new treatment strategies. Blood samples and tissue biopsies are collected during surgeries, biopsies, or diagnostic tests. Researchers use advanced molecular techniques like single-cell RNA sequencing to examine tumor heterogeneity and the liver environment, aiming to discover new biomarkers and treatment predictors. Participants will undergo procedures as part of their care, including hepato-bilio-pancreatic surgery, biopsies, or locoregional treatments. Blood samples are taken during these procedures to support research. Researchers will monitor surgery outcomes over an average of eight years. By studying patient samples and clinical data, the team aims to improve personalized medicine approaches and identify new preventive and therapeutic targets for chronic liver diseases and liver cancer.

Chronic hepatitis B virus (HBV) infection is a major global health issue that can lead to serious liver problems such as cirrhosis, liver cancer, and death. This observational study aims to gather detailed information from a broad group of Chinese patients with chronic HBV infection to better understand the factors that influence disease outcomes. The study involves creating a comprehensive database of clinical, epidemiological, biological, virological, immunologic, and treatment-related data from patients with chronic HBV infection. There are no drug interventions; instead, participants are monitored as part of this long-term cohort. Participants will be followed over many years, with researchers tracking outcomes like loss of hepatitis B antigens, development of cirrhosis, liver failure, liver cancer, and mortality. Regular assessments will collect relevant health information to help identify the factors linked to disease progression. The study is planned to continue until 2030, providing extensive long-term data on chronic HBV infection.

Researchers are studying the metabolism of cells in the ascites fluid of ovarian cancer patients to better understand the tumour environment. This observational study involves women aged 18 and older who have ascites caused by diagnosed ovarian cancer. The study aims to trace how glucose is taken up and metabolized by tumour and T cells in the ascites. Participants will receive an intravenous infusion of specially labeled glucose ([U-13C]glucose) during their scheduled paracentesis procedure. The infusion starts with 8 grams of labeled glucose in 60 mL over 10 minutes, followed by 4 grams in 30 mL over one hour, continuing until the ascites fluid is drained or up to 5 hours. A continuous glucose monitor tracks blood glucose levels throughout. Samples of ascites fluid collected during the infusion will be kept on ice and analyzed for metabolic activity and metabolite profiles using flow cytometry and mass spectrometry. During the study, participants will wear a glucose monitor before paracentesis and have ascites fluid collected hourly for up to 5 hours. Researchers will measure glucose enrichment and compare metabolic pathways in different cell types within the ascites. They will also correlate metabolic profiles with T cell function. The study involves close monitoring of blood glucose and sample analysis to understand tumour and immune cell metabolism in ovarian cancer ascites.

Researchers are studying the use of spleen shear wave elastography (SWE-SSM) to help diagnose significant portal hypertension and high-risk esophageal varices in patients with advanced compensated chronic liver disease. The study aims to understand how well SWE-SSM can identify these conditions without affecting patient treatment or disease progression. It also explores how SWE-SSM relates to portal pressure and transient elastography measurements in some patients. During the ultrasound exams that patients normally undergo, spleen elastography will be added if the patient meets study criteria and consents. This additional test is non-invasive and does not change the standard ultrasound procedure or patient care. No treatments or experimental interventions will be given, as the study focuses on collecting clinical data through observation. Participants will have ultrasound exams including both spleen and liver elastography as part of their usual care pathway. Researchers will evaluate measurements related to portal hypertension and esophageal varices over a two-year period. The study monitors the natural course of the disease and gathers data without altering treatments or clinical management.

Researchers are investigating new non-invasive methods to predict hepatic venous pressure gradient (HVPG), a key measure in managing portal hypertension in cirrhosis. This study compares three-dimensional magnetic resonance elastography (3D-MRE) with two-dimensional magnetic resonance elastography (2D-MRE) to develop a risk stratification system that can guide personalized treatment for portal hypertension. Cirrhosis and portal hypertension pose significant health challenges, making less invasive diagnostic tools important for patient care. Participants will undergo imaging using either 3D-MRE or 2D-MRE, both performed on a 3.0-T MRI system with an eight-channel body coil. The study features two groups: one developing a model using 3D-MRE and a control group using 2D-MRE. Hepatic venous pressure gradient measurements are taken by trained radiologists following standard procedures. Comparing these imaging techniques aims to evaluate their accuracy in assessing portal hypertension. During the study, participants will have imaging and HVPG measurements within one month to ensure data consistency. Researchers will assess the accuracy of 3D-MRE and 2D-MRE features for predicting portal hypertension over a 12-month period. The study monitors participants through these diagnostic tests and evaluates how well the imaging models can predict HVPG, contributing to safer, more convenient management of cirrhosis-related complications.

Researchers are evaluating a new, non-invasive method using three-dimensional magnetic resonance elastography (3D-MRE) to predict hepatic venous pressure gradient (HVPG) in patients with cirrhosis, portal hypertension, or advanced chronic liver disease. This study aims to establish a risk stratification system to better manage portal hypertension, a critical factor affecting the prognosis of these liver conditions. The trial is observational and focuses on improving diagnosis without invasive procedures like liver biopsy or traditional HVPG measurement. The study involves two groups: a training cohort to develop the new 3D-MRE model for virtual HVPG prediction, and a validation cohort to confirm the model's accuracy in different patients under similar conditions. Imaging is done using a 3.0-T MRI system with a phased-array body coil, while HVPG measurements are performed by skilled interventional radiologists following standard procedures. Participants undergo both assessments within one month. During the 12-month study, participants will have their portal hypertension assessed through the features of 3D-MRE and HVPG readings. Researchers will analyze the accuracy of 3D-MRE to predict portal hypertension levels. Participants provide informed consent and meet age and health criteria. The study includes monitoring to ensure reliable imaging and measurement results, with exclusion of those with conditions or treatments that may affect accuracy. The total participation involves these diagnostic steps, with no treatment interventions administered.

Researchers are evaluating super Hi-TCR-T cells targeting multiple proteins including Nectin4, NKG2DL, TROP2, B7H3, GPC3, and FAP for treating patients with advanced hepatocellular carcinoma (HCC) and other solid tumors that have not responded to prior treatments or cannot tolerate them. This prospective, single-arm clinical trial aims to assess the safety, tolerability, and effectiveness of this cell therapy, focusing on progression-free survival as a primary outcome. The study also explores quality of life, disease control rates, overall survival, and potential biomarkers related to therapy response. The treatment involves collecting peripheral blood lymphocytes from patients to prepare customized Hi-TCR-T cells targeting three selected proteins, including FAP. Patients undergo chemotherapy pretreatment with fludarabine and cyclophosphamide before receiving an intravenous infusion of these cells at a dose of 3.0 x 10^6 cells per kilogram of body weight for each target. As the disease progresses, the cell dose or target combination may be adjusted by a multidisciplinary team to improve efficacy. The study includes preparatory, recruitment and treatment, and data analysis phases spanning several months. Participants will undergo baseline assessments including physical exams, lab tests, imaging, and tumor marker evaluations before treatment. Safety monitoring occurs frequently after cell therapy at multiple time points up to 12 months, alongside efficacy evaluations at intervals up to 36 months post-treatment. Blood samples are collected periodically to study the persistence and expansion of the infused cells and their relation to disease changes. The study duration covers the treatment period plus follow-up until 12 months after the last patient's medication ends or other defined endpoints.

Researchers are evaluating the effectiveness of SHR-8068 combined with Adebrelimab and Bevacizumab compared with Sintilimab or Atezolizumab combined with Bevacizumab as first-line treatments for advanced hepatocellular carcinoma (HCC). This phase III clinical trial focuses on patients with unresectable locally advanced or metastatic HCC, aiming to understand how these drug combinations perform in managing this serious liver cancer. Participants receive intravenous infusions of study drugs according to their assigned group. One group receives SHR-8068, Adebrelimab, and Bevacizumab, while the other group receives either Sintilimab combined with Bevacizumab or Atezolizumab combined with Bevacizumab. The study is randomized and open-label, meaning patients are randomly assigned to a treatment group and both patients and researchers know which treatment is given. Treatments are delivered by injection in cycles as per the study protocol. During the study, participants undergo regular assessments to monitor disease progression and treatment effects, including imaging evaluations based on RECIST v1.1 criteria reviewed by an independent committee. Researchers measure progression-free survival, overall survival, response rates, duration of response, and adverse events up to approximately 36 months. Participants are closely monitored for safety throughout the study, with follow-up visits to evaluate ongoing effects and health status.

Wilson's disease is a rare inherited disorder caused by mutations in the ATP7B gene, leading to copper buildup in organs like the liver, brain, and kidneys. Researchers are evaluating LY-M003 Injection, a gene therapy using an rAAV8 vector, to deliver the ATP7B gene to liver cells. This study aims to assess the safety, tolerability, effectiveness, immune response, and how the body processes this therapy in patients with Wilson disease. The study uses a single intravenous infusion of LY-M003 at one of four dose levels, ranging from 1.0 to 6.0 x 10^13 vector genomes per kilogram. There are adult and pediatric groups, with dose escalation decisions based on safety and effectiveness data. Adult participants receive one of four dose levels, while pediatric dosing is determined after reviewing adult results. The study has a main phase and a long-term follow-up phase to monitor outcomes. Participants will be followed for 52 weeks after receiving the infusion. During this time, researchers will monitor adverse events, dose-limiting toxicities, changes in copper-related lab tests, liver function, neurological and psychiatric symptoms, and liver stiffness. They will also track reductions in standard Wilson disease medications. This comprehensive monitoring includes clinical assessments and laboratory tests to evaluate how participants respond to LY-M003 therapy over time.

Researchers are evaluating the safety and tolerability of Efimosfermin Alfa in adults aged 18 to 75 years who have known or suspected metabolic dysfunction-associated steatohepatitis (MASH) with liver fibrosis at stages F2 or F3. This phase 3, randomized, double-blind, placebo-controlled study aims to better understand how this drug affects participants with this liver condition related to metabolic syndrome components. Participants will be randomly assigned to one of three groups: one receiving Efimosfermin Alfa at dose level 1, another receiving Efimosfermin Alfa at dose level 2, and a third group receiving a placebo. The study will monitor the effects of these treatments over a period of 52 weeks, assessing safety and tolerability as well as changes in liver fibrosis markers and other related health measures. During the trial, participants will undergo regular assessments including laboratory tests, imaging scans such as MRI and elastography to measure liver stiffness and fat content, and blood tests to monitor liver enzymes and metabolic markers. Researchers will track treatment-emergent adverse events and laboratory abnormalities. The study involves continuous monitoring up to week 52 to evaluate changes from baseline and to ensure participant safety throughout the trial.