Chronic 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 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.

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.

Researchers are investigating early detection and risk assessment of hepatocellular carcinoma (HCC) in adults with advanced liver disease, specifically those with liver cirrhosis from various causes. This prospective multicenter study aims to compare ultrasound and abbreviated MRI (AMRI) as surveillance tools to assess their ability to detect HCC, as well as to study how body composition, such as fat and muscle levels, relates to disease progression and HCC risk. Participants with cirrhosis undergo regular clinical evaluations and imaging tests at set intervals, including ultrasound and abbreviated MRI scans. The study collects detailed data on body composition and tracks clinical outcomes like liver-related complications and mortality. These assessments occur over multiple visits, including baseline and follow-ups at 6, 12, and 18 months, with additional monitoring for up to 24 months to observe new cases of HCC and disease progression. During the study, participants receive structured exams, imaging, and body composition measurements at each visit. Researchers evaluate lesion risk for HCC using LI-RADS criteria and measure muscle mass through the Muscle Assessment Score. They also monitor liver stiffness and organ volumes at baseline and follow-up visits. The study's goal is to develop prediction models based on these clinical and imaging data to better understand HCC risk and liver disease progression over time.

Researchers are investigating the appropriate intensity of rehabilitation programs for patients who have undergone liver transplantation. Cardiovascular disease is a leading cause of death for these patients due to sedentary lifestyle and poor physical fitness after transplant. The study aims to test a structured, home-based, supervised physical rehabilitation and maintenance program in liver transplant recipients, assessing its feasibility, safety, and ability to improve physical fitness. Participants will be randomly assigned to one of three training groups with different exercise intensities: low, moderate, or combined moderate and high intensity. The rehabilitation program lasts six months and includes aerobic, strength, balance, and flexibility exercises performed from home under supervision. After this, a 15-month maintenance phase of physical activity tailored to individual preferences will follow to observe long-term implementation. Participants will undergo assessments at the start, three months, six months, and 15 months after the intervention begins. These evaluations include tests of physical fitness, cardiovascular health, liver function, body composition, and questionnaires monitoring well-being, safety, quality of life, physical activity, and cost-effectiveness. Monthly monitoring of adverse events and follow-ups at the study site will ensure safety and track outcomes over time.