Wilson Disease

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 conducting a prospective multicenter observational study to better understand Wilson's Disease, focusing on its clinical spectrum and natural progression. The study also aims to explore clinical, genetic, epigenetic features, and biomarkers associated with Wilson's Disease to improve patient care and management. This study does not involve any medical interventions or treatments. Instead, participants are classified into groups including patients genetically diagnosed with Wilson's Disease, asymptomatic carriers, relatives of patients or carriers, and unrelated healthy controls. The study follows these groups over time without altering their usual care. Participants will be regularly evaluated using the Unified Wilson's Disease Rating Scale (UWDRS) over a period that may extend up to 30 years. The study involves collecting clinical data and monitoring changes in symptoms and biomarkers. This long-term follow-up helps researchers track the disease's progression and gather valuable information to support future treatment strategies.

Researchers are investigating the relationship between the volume of normal liver tissue removed during surgery, called resected normal liver parenchymal volume (RNLV), and the risk of liver failure after liver surgery (post-hepatetotomy liver failure, or PHLF). This observational study focuses on patients diagnosed with hepatocellular carcinoma (HCC) or intracholangiocarcinoma (ICC) who have undergone liver resection. The goal is to build and assess a personalized predictive model using RNLV to better estimate the risk of PHLF before surgery. The study collects data retrospectively from over a thousand patients treated at the investigator’s center. Patients are grouped based on whether they developed liver failure after surgery, defined by two sets of criteria known as the 50-50 criteria and ISGLS criteria. The research evaluates how well the RNLV-based model predicts PHLF and compares its usefulness to other methods, especially for patients with large or multiple liver tumors. Participants' medical records and surgical details are reviewed to calculate RNLV and assess liver failure outcomes within 30 days after surgery. The main outcome is the predicted probability of PHLF using the newly developed model. This approach aims to improve preoperative risk assessment to support safer liver surgeries. The study is sponsored by the National Natural Science Foundation of China and runs through the end of 2026.

Robotic surgery is an advanced technology designed to improve minimally invasive liver surgery by enhancing flexibility and precision. This research focuses on comparing robotic liver resection with laparoscopic and open liver resections to evaluate its safety and feasibility. The study aims to provide clear and relevant data about the potential benefits and challenges of using robotic systems in liver surgery. Participants will undergo robotic liver resection using the Da Vinci robotic system. The study compares this approach with traditional laparoscopic and open methods, aiming to assess differences in surgical outcomes. The robotic method is studied as a device intervention, with careful observation of its use in liver tumor removal. Throughout the study, researchers will monitor participants for complications within 90 days after surgery, including hospital stay length, any unplanned reoperations, and readmissions. These outcomes help determine the safety and recovery aspects of robotic liver surgery. Participants will be followed during this postoperative period to gather comprehensive data on their surgical experience and recovery.

Researchers are evaluating the impact of a transitional care model called the Transitional Liver Clinic (TLC) on patients with advanced liver disease who face challenges after hospital discharge. This trial seeks to reduce early hospital readmissions, improve quality of life, and enhance patient experience during this vulnerable period. The study is designed as a stepped-wedge randomized trial conducted across four large centers over 45 months, including about 1,000 patients with advanced liver disease. Participants will receive either usual care or the TLC intervention. Those in usual care will be followed by their regular providers based on discharge recommendations. Patients in the TLC group will get a phone call from TLC staff within two business days after discharge and an in-person or telehealth clinic visit with a hepatology advanced practice provider within 14 days. Additional care tailored to individual patient needs is provided during the 30-day transitional period. Each site transitions from usual care to TLC sequentially during the study periods. Participants are followed up by phone at 30 and 90 days after discharge to assess outcomes. The study measures include 30-day hospital readmission rates, quality of life using the Promis 29+2 survey, and patient satisfaction via the PSQ 18 questionnaire. Secondary outcomes include emergency room visits, mortality at 90 days, days alive outside the hospital, and hospital readmissions at 30 and 90 days. The total participation spans the hospitalization and follow-up periods, with close monitoring of patient health and experience.

This research aims to evaluate whether normothermic machine perfusion (NMP) can safely increase the number of usable donor livers for transplantation, helping patients get transplants faster and improving outcomes. The study focuses on patients waiting for a liver transplant with a ReMELD-Na-Score of 21 or less, who do not meet certain special exception criteria. It investigates if this new assessment method reduces waiting time and improves survival and health after transplant. Participants are randomly assigned to one of two groups. The experimental group may receive livers initially declined by all German transplant centers but deemed suitable after at least four hours of NMP quality assessment. The control group receives livers through the usual transplant process. Declined livers are selected based on specific quality criteria such as steatosis less than 60%, fibrosis grade up to F3, and graft weight between 1 and 2.5 kg. During the study, researchers track how quickly participants receive a transplant as the main outcome. They also monitor survival rates, disease progression, recovery on the waitlist, quality of life, graft utilization, hospital stay costs, and complications up to 24 months after randomization. Participants will be followed for up to 12 months to observe transplant timing and up to 24 months for longer-term outcomes.

Researchers are evaluating how well neural networks trained on ultrasonic raw radiofrequency data can assess liver diseases in patients undergoing clinical ultrasound exams. The study aims to compare the performance of these neural networks against elastography and those trained on b-mode ultrasound images, as well as to see if they can distinguish focal liver lesions from healthy tissue. This research is conducted with patients who have a clinical indication for elastography or suspected liver lesions and involves collecting detailed ultrasound data for analysis. Participants scheduled for elastography will have both b-mode images and radiofrequency data collected during their ultrasound scans. For those with suspected focal liver lesions, ultrasound data is collected along with a definitive diagnosis obtained through standard clinical procedures such as contrast-enhanced ultrasound, biopsy, MRI, or CT, depending on what is normally done at the participating center. The study includes two groups: one focused on elastography data collection and another on focal lesion evaluation, all without randomization or masking. During the study, participants undergo clinical ultrasound examinations to capture both b-mode images and corresponding radiofrequency data. Additional tests or procedures may be performed to confirm diagnoses for focal liver lesions. Researchers will analyze the performance of the trained neural networks after the study concludes, approximately one year later. The total participation time varies, with assessments aligned to routine clinical care. Safety monitoring includes exclusion of recent liver interventions to avoid confounding results.

This observational study focuses on liver transplant patients who are taking tacrolimus-containing medications. It aims to compare the pharmacokinetic parameters of different tacrolimus products and examine their relationships to liver function, kidney function (estimated glomerular filtration rate), and patient adherence. The study also monitors the occurrence of acute graft rejection and infections such as BK and cytomegalovirus during the observation period. This research addresses the lack of real-life data on immunosuppressive drug effectiveness and safety in liver transplant patients across Europe. Participants are liver or simultaneous liver-kidney transplant recipients aged 18 years or older who have been on tacrolimus-containing immunosuppressant therapy for at least four weeks before joining. Various tacrolimus medications, including Envarsus, Adport, Advagraf, Modigraf, Prograf, and Tacforius, are used under routine clinical care following local dosing guidelines. The study observes patients over a 24-month period without changing their prescribed treatments. During the study, participants undergo routine clinical visits and tests as part of their standard care, with no additional procedures required. Researchers collect data on tacrolimus blood levels, daily doses, and their variability, alongside liver and kidney function tests. Adherence is assessed using the BAASIS questionnaire and electronic health records of prescription fills. Outcomes such as graft rejection, infection rates, and drug tolerability are evaluated over 12 months, with ongoing monitoring for up to two years.

Researchers are evaluating the effectiveness and safety of a combination treatment involving blank-microsphere transcatheter arterial embolization (bTAE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, 5-fluorouracil, and leucovorin, together with the drugs Lenvatinib and Sintilimab, for patients diagnosed with infiltrative hepatocellular carcinoma. This prospective, single-arm study aims to provide new insights since no prior study has assessed this specific combination. The trial is sponsored by Sun Yat-sen University. The treatment involves a bTAE procedure where a microcatheter is carefully inserted into the artery feeding the tumor, followed by the use of blank microspheres sized according to the tumor blood supply vessels. Afterward, chemotherapy drugs (oxaliplatin, fluorouracil, and leucovorin) are infused via the hepatic artery every four weeks. Participants take Lenvatinib orally once daily and receive Sintilimab infusions every three weeks. This combined treatment is studied to assess its impact on tumor response and patient survival. Participants will undergo regular assessments including imaging and laboratory tests to monitor tumor response and safety. The primary outcome measured is the objective response rate at six months. Secondary outcomes include progression-free survival at six months and overall survival at twelve months. The study will monitor participants throughout the treatment period, including evaluations of liver function, blood counts, and overall health status, with the total participation duration varying by individual.

Researchers are evaluating a combination treatment involving blank-microsphere transcatheter arterial embolization and hepatic arterial infusion chemotherapy (bTAE-HAIC) with the drugs oxaliplatin, 5-fluorouracil, and leucovorin, along with Lenvatinib and Camrelizumab for patients who have intermediate to advanced large hepatocellular carcinoma (liver cancer). This prospective, single-arm study aims to assess the safety and effectiveness of this combined approach, as previous studies have shown individual treatments to be effective but not in this combination. The treatment involves a procedure where a microcatheter is inserted into the artery feeding the tumor, and blank microspheres are delivered based on the tumor's blood supply. After this, chemotherapy drugs are infused directly into the hepatic artery every four weeks. Alongside this, patients receive daily oral Lenvatinib and intravenous Camrelizumab every two weeks. The study focuses on this combination therapy without a comparison group. Participants will be monitored over six months to measure the objective response rate to the treatment. Assessments include clinical evaluations and laboratory tests to monitor liver function, blood counts, and other safety markers. Researchers will also track progression-free survival and other outcomes. The study lasts until December 2025, with careful safety monitoring throughout to evaluate the treatment's effects on tumor response and patient health.