Cholestatic liver disease

The purpose of this study is to determine whether the investigational treatment (maralixibat) is safe and effective in pediatric and adult participants who have cholestatic liver disease with pruritus that has been refractory to other therapies, and who have no other treatment options.

Purpose The primary purpose is to use an imaging diagnostic method to examine how the medication for primary biliary cholangitis (PBC) works. This will be studied using a radioactive tracer that behaves like human bile and can be observed with a PET/CT scanner. The aim is to gain insight into the disease mechanisms and how the medication affects them.
The standard treatment for PBC is ursodeoxycholic acid, also known as Ursochol, which stimulates bile flow. If treatment with Ursochol is insufficient, bezafibrate can be added. The effectiveness of treatment is currently monitored through blood tests, which do not necessarily reflect the severity of the liver disease. However, this can be assessed using advanced PET/CT scans with a radioactive tracer, 11C-CSAR, which quickly clears from the body.
The purpose of this study is to use the method to show how 11C-CSAR moves through the liver and bile ducts in PBC patients before and after treatment with either Ursochol or a combination of Ursochol and bezafibrate.
We aim to:
* Observe how the disease affects the liver's handling of bile salts and how this changes with medication.
* Determine the excretion kinetics of 11C-CSAR, including specific rate constants.
* Assess changes in liver blood flow before and after treatment.
* Compare routine blood tests with 11C-CSAR PET/CT findings to evaluate how well blood tests reflect actual liver involvement.
Study Plan The scientific study involves two examination days. Both days follow the same procedure. Participants must arrive fasting on the examination day. An intravenous catheter will be placed in each arm, a catheter in a wrist vessel, and a liver vein catheter. The liver vein catheter will be inserted by a trained liver doctor through a small sheath in a neck vein, guided by ultrasound, and the final placement will be confirmed with fluoroscopy. The tracer 11C-CSAR and the dye indocyanine green (ICG) will be administered through the intravenous lines. ICG will be given as a constant infusion 90 minutes before the scan to distribute in the tissue. The tracer will be injected just before the scan. Blood samples will be taken from the liver catheter and wrist catheter during the scan, which lasts approximately 45 minutes. After the scan, the catheters will be removed, and the participant can leave shortly afterward. About 250-300 ml of blood will be drawn during the scan, which will have no significant impact on participants. The entire process is expected to take about four hours.
Study Participants Our goal is to include 20 newly diagnosed PBC patients and 10 patients who do not respond to standard treatment and are about to begin bezafibrate. Some participants may complete both parts of the study. If newly diagnosed patients do not respond sufficiently to Ursochol and need to start bezafibrate while the study is ongoing, they may participate both before and after starting Ursochol and bezafibrate.

Purpose The primary goal is to study liver diseases with defects in bile excretion. Investigators aim to do this using a radioactive tracer that mimics human bile and can be visualized with a PET/CT scanner. This will help us understand where these defects occur and how they might be treated in the future.
Background Patients with liver diseases affecting bile excretion are at risk of developing cirrhosis. When bile cannot be excreted normally, it accumulates in the liver, damaging its function. It can also build up in the skin, causing yellowing and itching. Currently, patients are monitored using blood tests that do not always reflect the severity of liver disease. There are a few medications available, but they have limited efficacy.
Advanced PET/CT scanning with the radioactive tracer 11C-Csar offers a way to investigate this. 11C-Csar has been developed, tested, and approved for human use at Aarhus University Hospital and has been used in previous patient studies.
The study aims to use this method to show how 11C-Csar moves through the liver and bile ducts in both healthy individuals and patients with a genetic liver disease. Investigators aim to:
* Observe how defects affect the liver handling of bile acids.
* Determine the excretion kinetics of 11C-Csar, including specific rate constants.
* Compare standard blood tests with 11C-Csar PET/CT findings to assess how well blood tests reflect actual liver damage.
* Visualize potential targets for future interventions.
Study Plan The scientific study involves a single examination day at the Department of Nuclear Medicine and PET. Participants will arrive fasting in the morning. An intravenous line will be placed in both arm veins, a catheter in a wrist vessel, and a hepatic vein catheter. The hepatic vein catheter will be inserted by a trained liver specialist using local anesthesia and ultrasound guidance, confirmed by X-ray. The tracer 11C-Csar and the dye indocyanine green (ICG) will be administered through the IV lines. ICG will be infused 90 minutes before scanning, and 11C-Csar will be administered at the start of the scan. Blood samples will be taken from the liver and wrist during the scan, which lasts about 45 minutes. After the scan, the catheters will be removed, and the participant can go home shortly after. Approximately 250-300 ml of blood will be drawn, which poses no risk to the participants. The total participation time is expected to be around 4 hours. Some patients may be offered a second scan if they develop new symptoms, repeating the scan when liver blood tests normalize.
Participants Patients with bile accumulation liver diseases will be informed of the study during visits to the Department of Hepatology and Gastroenterology, AUH. Healthy controls will be recruited through advertisements on webpages dedicated for the purpuse. Interested individuals will receive written information.
Side Effects, Risks, and Discomfort The risk of phlebitis and bleeding from IV insertion is minimal, as these procedures are performed daily.
The total radiation exposure from the PET/CT scan with 11C-Csar is 2.5 mSv.
Funding The study is researcher-initiated, with no financial interests for the involved researchers.
Publication of Results Both negative, positive, and inconclusive results will be published. The study results will be submitted to peer-reviewed international journals in liver disease and/or radiology and presented at national and international scientific conferences.
Ethics The study will be conducted following the principles of the Helsinki Declaration II with amendments and after approval by the Regional Ethics Committee for Midtjylland. While there is no immediate benefit for patients, the results will enhance our understanding of liver disease with bile acid accumulation. Investigators believe the risks and potential side effects are outweighed by the expected benefits.