Cholestasis

Researchers are observing the use of maralixibat (TAK-625) in Japanese patients diagnosed with Alagille Syndrome (ALGS) or Progressive Familial Intrahepatic Cholestasis (PFIC). The main goal is to evaluate the risk of liver disorders during treatment with maralixibat. This study uses data from the Comprehensive and Informative Registry system for Childhood Liver Disease (CIRCLe) to gather information on these patients. The study groups include participants with ALGS and participants with PFIC, all of whom have received maralixibat oral solution according to the official prescribing information. The research involves analyzing existing medical records and prescriptions within the CIRCLe database to assess liver disorder risks over a period of up to six years. Participants' liver health is monitored through evaluations of liver disorder occurrence and the timing of onset using defined outcome measures for side effects and adverse events. Researchers will review the percentage of patients experiencing liver disorders and how soon these occur after starting maralixibat treatment, using data collected over several years. The study does not involve direct intervention but relies on existing registry and medical data.

Researchers are evaluating new strategies for preoperative biliary drainage in patients with resectable pancreatic head cancer who have severe obstructive jaundice. This trial compares a modified drainage approach using serum prealbumin levels as the main evaluation marker against the traditional approach relying on serum total bilirubin levels. The study aims to determine the impact of these strategies on in-hospital complications and long-term outcomes, providing evidence to guide clinical decisions on drainage timing and surgery scheduling. Participants will be randomly assigned to one of two groups: one receiving the traditional preoperative biliary drainage strategy based on total bilirubin, and the other receiving the modified strategy based on prealbumin levels. Both groups will undergo endoscopic biliary drainage (ERCP) prior to radical pancreaticoduodenectomy surgery. The study is multicenter, open-label, and controlled, with treatment and evaluation occurring before surgery. During the study, patients will be monitored for complications during hospitalization up to three months after treatment. Researchers will also track recurrence or metastasis, mortality, and long-term complications up to 12 months after discharge. Assessments include clinical evaluations and laboratory measurements to monitor drainage effectiveness and patient safety. The total duration of participation includes preoperative evaluation, treatment, and follow-up over one year to assess outcomes comprehensively.

Researchers are studying infants with cholestasis, including conditions like biliary atresia and idiopathic neonatal hepatitis that cause prolonged jaundice and high bilirubin levels after the newborn period. The Childhood Liver Disease Research Network (ChiLDReN) aims to create a database of clinical information and biological samples from affected children to support research and clinical trials on these serious liver diseases in children. This project collects detailed clinical data, laboratory results, and biological samples such as blood and tissue from infants diagnosed or suspected to have biliary atresia or other neonatal liver diseases. Infants diagnosed with biliary atresia are followed closely during their first year, at 18 months, annually up to age 10, and then every two years, or until liver transplantation occurs. Infants with other cholestatic diagnoses exit the study after diagnosis is confirmed. Participants undergo routine clinical care and evaluations, with data entered into a secure national research database. Blood samples are collected during clinically indicated procedures when possible. Researchers measure disease progression over time at multiple intervals from baseline through 20 years of age. The study involves long-term follow-up of outcomes and data are securely stored and eventually transferred to a national data repository.

Researchers are investigating the use of 18F-DFA PET imaging to evaluate liver injury, a condition involving rapid liver function decline with symptoms like increased liver enzymes, jaundice, and abdominal discomfort. This observational study aims to assess how accurately this imaging method detects liver damage compared to standard clinical biochemical tests and liver biopsy, which is the current gold standard despite its sampling limitations. The study focuses on adults clinically diagnosed with liver damage or liver failure, exploring the correlation between 18F-DFA uptake in the liver and liver function indicators. Participants diagnosed with liver injury will undergo 18F-DFA PET imaging as part of the study. This radioactive tracer, based on vitamin C structure, is used to visualize liver function non-invasively. The imaging process involves a PET-CT scan lasting about 10 minutes, followed by a one-hour waiting period in the examination room before leaving. The study will compare imaging results with clinical liver function tests or liver biopsy findings to determine the sensitivity and specificity of this method. During the study, participants will have their liver function monitored using PET-CT scans and clinical biochemical markers. The primary outcomes include changes in liver uptake values on PET imaging at 6 months and the relationship between imaging results and standard liver function indicators. Participants will be followed up as needed, with assessments including liver enzyme levels and other blood tests. The total study duration depends on individual follow-up, and safety monitoring will address any issues related to PET imaging procedures.

Researchers are evaluating NST-6179 in a phase 2a, multicenter, randomized, double-blind, placebo-controlled study involving adults with intestinal failure-associated liver disease (IFALD) who receive parenteral nutrition. The study focuses on assessing the safety, tolerability, pharmacokinetics, and pharmacodynamics of NST-6179, a drug under investigation, with up to 36 participants divided into two sequential parts. In Part A, participants will receive 800 mg of NST-6179 or a matching placebo once daily by mouth for 4 weeks. In Part B, the planned dose is 1200 mg once daily for 12 weeks, though the exact dose will be determined after a safety review. Subjects will be randomized in a 2:1 ratio to receive either NST-6179 or placebo in both parts of the study. Participants will undergo regular assessments including safety and tolerability evaluations up to 14 weeks, pharmacokinetic measurements on Days 1 and 14, and pharmacodynamic evaluations over 12 weeks focusing on liver fat, inflammation, cholestasis, and fibrosis markers. The study involves laboratory tests and monitoring to track how the drug affects liver function and disease progression throughout the treatment periods.

Researchers are evaluating the investigational drug volixibat for treating itching (pruritus) caused by Primary Biliary Cholangitis (PBC), a liver disease. This Phase 2 clinical trial aims to learn more about volixibat's effects on itching and its potential impact on PBC disease progression. The study is sponsored by Mirum Pharmaceuticals, Inc. Participants are randomly assigned to one of several groups receiving either volixibat capsules at doses of 20mg or 80mg twice daily, or placebo capsules without the active drug, also taken twice daily. The trial includes two parts, with some participants receiving volixibat 20mg twice daily and others receiving matching placebo capsules. The study is double-blind, meaning neither participants nor researchers know which treatment is given. During the study, participants' itching levels are monitored using the Adult Itch Reported Outcome questionnaire over 28 weeks. Researchers also assess quality of life, fatigue, sleep disturbance, liver function tests, bile acid levels, and adverse events. Participants will attend regular visits for assessments, and the main outcome measured is the change in daily itch scores from baseline to week 28. The study excludes healthy volunteers and focuses on adults aged 18 years and older with confirmed PBC.

Chronic liver diseases affect over 800 million people worldwide and cause about 2 million deaths each year. Early diagnosis and prediction of disease progression remain major challenges, as current blood markers and panel tests lack sensitivity and specificity. This research focuses on albumin post-translational modifications (PTM) as potential early biomarkers that may indicate future liver damage and help predict disease progression in patients with chronic liver disease. The study will recruit 756 patients with compensated fibrosis from six university hospitals and follow them for up to three years. Blood samples will be taken at the start and during follow-up visits at one, two, and three years, either through additional tubes added to routine samples or using leftover samples. These will be analyzed centrally to assess albumin isoform profiles and ligand-binding capacities using the Serum Enhanced Binding (SEB) test. Participants will have no extra visits beyond their usual care appointments. Data including blood results and medical records will be collected at each visit. Researchers will evaluate the ability of albumin modifications and the SEB test to predict liver disease progression, monitor changes over time, and confirm characteristic albumin patterns related to liver injury. The study aims to improve liver disease diagnostics and patient care by validating these novel biomarkers.

Researchers are evaluating patients with chronic liver diseases linked to hepatic steatosis, a condition where fat accumulation in the liver may cause inflammation and scarring. This condition can lead to serious liver problems such as cirrhosis, liver failure, and death. The study aims to better understand the underlying mechanisms of these diseases and to identify specific diagnostic markers and potential future treatments by examining tissue-level characteristics. This observational study involves collecting detailed biological samples and data from adults with various chronic liver diseases, including autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, hereditary hemochromatosis, alpha-1-antitrypsin deficiency, and others. The study does not involve any drug or device interventions but focuses on in-depth phenotyping and metabolic assessments at multiple time points. Participants will be observed and evaluated over a period of up to 10 years. Researchers will collect plasma samples at several intervals and aim to identify diagnostic classifiers to distinguish between different chronic liver diseases. The study includes regular assessments and long-term monitoring to gather comprehensive data on metabolic disturbances and disease characteristics. Participation involves informed consent and adherence to scheduled evaluations without treatment administration.

This research aims to understand whether an immune process similar to allograft rejection causes intrahepatic cholestasis of pregnancy (ICP). The study includes pregnant women with and without ICP to explore if immunomodulatory treatments might be helpful. It is an observational study conducted by the University Hospital, Brest, focused on inflammation in ICP. The study involves 322 pregnant women at delivery, divided into two groups: 161 women diagnosed with ICP and 161 without ICP. Blood tests will be performed on both mothers and newborns to measure various biological markers related to inflammation, allograft rejection, and angiogenesis. Placental tissue will also be analyzed to check for chronic inflammation. Participants will provide blood samples and placenta at delivery for detailed analysis. Researchers will compare biological and placental markers between the ICP and non-ICP groups. The main outcome measured is the prevalence of placental chronic inflammation at delivery, alongside levels of biological factors involved in inflammation, rejection, and angiogenesis. The study will monitor these outcomes at delivery and conclude by June 2025.

Biliary atresia is a severe liver disease affecting children, leading to high illness and death rates, with symptoms like intense itching, fatigue, poor growth, liver failure, and impaired brain development. The cause is mostly unknown, and over half of affected children need a liver transplant during childhood. Determining the best time for transplantation is difficult due to lack of consensus based on clinical tools. This research aims to find risk factors for brain-related problems in these children to help decide the optimal transplant timing from a neurological perspective. The study will observe 75 children aged 0 to 18 years with biliary atresia in Denmark, along with 30 healthy children and 20 with tetralogy of Fallot as comparison groups. Participants will undergo detailed evaluations including liver function tests, genetic profiling, nutrition and immune status assessments, brain imaging (MRI), and neurocognitive tests at diagnosis, ages 2, preschool, pre-teen, and teenage. Additional neurocognitive tests will be done if a liver transplant occurs. The study involves advanced monitoring of brain, heart, gut, and immune functions. Children in the study will have regular assessments of their neurocognitive abilities using various tests and brain MRIs at multiple ages. Liver and heart function will be closely evaluated through imaging and lab tests. Researchers will also analyze genetics and microbiome samples. The main outcomes include brain MRI and multiple neurocognitive tests to evaluate development and function. The study is observational and will follow participants over many years to track changes and outcomes related to biliary atresia and transplantation timing.