Restoring Bile Acid Homeostasis Via Lifestyle Adjustments to Prevent the Development of Liver Cancer

Prior treatment

• Use of weight-loss medications (e.g., GLP-1 agonists, Orlistat) within three months prior to enrolment or planned use during the study period.
• Current use of medications or supplements that significantly alter bile acid gastrointestinal absorption (e.g., bile acid sequestrants) that cannot be safely discontinued.

Other illness

• Patient with confirmed diagnosis of HCC by the American Association for the Study of the Liver Disease (AASLD) imaging criteria or histology / cytology within the last 5 years.
• Patient is known to be positive for the Human Immunodeficiency Virus (HIV).
• Patient has chronic liver diseases apart from steatosis or compensated cirrhosis (e.g., autoimmune hepatitis, primary biliary cholangitis. etc.).
• History of bariatric surgery or planned bariatric surgery during the study period.
• Patient has significant comorbidities expected to limit life expectancy to less than one year, or that would render diet or exercise unsafe
  • Diseases involving muscles, bones or joints that may impact the subjects' performance during exercise testing and exercise rehabilitation
  • Co-morbidities that may adversely affect exercise performance
  • Requiring an assistive aid with walking
  • Conditions that require strict dietary restrictions or impair ability to follow dietary interventions
• Patient has significant gastrointestinal diseases affecting nutrient absorption or requiring a special diet incompatible with study diet.
• Patient has severe food allergies or intolerances incompatible with the provided study diet.
• Patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.
• Patient has any other condition which, in the opinion of the Investigators, would make the patient unsuitable for enrolment or could interfere with completion of the study.

Lab values

• Uncontrolled diabetes mellitus requiring special dietary management or persistent unacceptable HbA1c levels.

Other

• The following criteria should be checked at the time of enrolment. If ANY applies, the patient must not be included in the study:
• Patient with Child Pugh C or decompensated cirrhosis at time of enrolment (based on the judgement of the Investigator).
• Patient with active hepatic encephalopathy at time of enrolment.
• Pregnancy or breastfeeding
• Patient is unable to provide informed consent or refuse blood taking and other investigations including LMS scans.

• The following criteria are to be checked at the time of enrolment. The patient may only be included in the study if ALL of the following statements are FULFILLED:
• The patient is an existing participant of the ELEGANCE study and shows no evidence of hepatocellular carcinoma (HCC) at the time of enrolment into RE-BALANCE.
• Male and female patients aged 50 to 90 years at the time of informed consent are eligible. However, patients with cirrhosis may be included if they are aged 40 to 90 years.
• Negative for hepatitis B surface antigen (HBsAg) and hepatitis C antibody
• High-risk bile acid profile, defined as a 12-non-hydroxy/12-hydroxy bile acid ratio below the threshold determined from ELEGANCE cohort data.
• Patient is able to comply with scheduled visits, assessments and other study procedures.
• Patient is willing to provide informed consent before enrolment in the study.