Understanding liver disease linked to alcohol and metabolic syndrome

CHronic Hepatopathies Associated With ALcohol Consumption aNd metAbolic Syndrome

This study is trying to find out what causes liver cancer in people with alcohol-related liver disease and fatty liver disease by looking at their health, diet, and immune system over several years.

Quick facts

• Study type: Observational
• Enrollment: 710 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France (Government)
• Drugs / interventions: methotrexate
• Locations: 1 site (Nice)
• Trial ID: NCT05623150 on ClinicalTrials.gov

What this trial studies

This observational study aims to identify metabolic and immune factors, along with medical imaging data, that contribute to the development of Hepatocellular Carcinoma (HCC) in patients with alcohol-related liver disease and Non-Alcoholic Steatohepatitis (NASH). It will include both cirrhotic and non-cirrhotic patients to uncover early molecular mechanisms leading to HCC. Participants will undergo a variety of assessments including dietary questionnaires, physical activity evaluations, and liver biopsies, with the collection of biological samples for future research. The study is expected to span over 10 years, with patient participation lasting from one day to two months.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a history of alcohol consumption and either diagnosed liver disease or at risk for developing HCC.

Not a fit: Patients with systemic treatment for HCC within the last six months or those unable to provide informed consent may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and early detection of liver cancer in patients with alcohol-related liver disease and metabolic syndrome.

How similar studies have performed: Other studies have shown promise in identifying metabolic factors related to liver disease, but this specific approach focusing on both alcohol-related and metabolic factors in a long-term observational setting is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Criteria common to all patients:

  1. Affiliation to French social security.
  2. Male or female ≥ 18 years of age
  3. Patients able to receive and understand information about the research and to give written informed consent duly signed by the patient and the investigator (at the latest on the day of inclusion and before any examination necessary for the research).
* Patients in the NAFLD group with HCC:

  1. Alcohol consumption ≤ 30 g pure alcohol/d (or 210 g pure alcohol/week) for men and ≤ 20 g pure alcohol/d (140 g pure alcohol/week) for women.
  2. Decision, less than 3 months old, of liver biopsy of the suspected HCC nodule and non-tumour liver tissue performed as a clinical routine.
  3. No systemic treatment for HCC within 6 months prior to inclusion.
* Patients in the NAFLD group without HCC:

  1. Alcohol consumption ≤ 30 g pure alcohol/d (or 210 g pure alcohol/week) for men and ≤ 20 g pure alcohol/d (140 g pure alcohol/week) for women.
  2. Decision of less than 3 months of a liver biopsy performed as a clinical routine. Biopsy will be motivated by liver function disturbance(s) and/or ultrasound steatosis given the lack of validated non-invasive tests or the lack of accuracy (grey areas) of available non-invasive tests for the diagnosis of necro-inflammation and/or fibrosis in some of these patients.
* Patients in the alcohol-related liver disease group with HCC:

  1. Alcohol consumption \> 30 g pure alcohol/d (or 210 g pure alcohol/week) for men and \> 20 g pure alcohol/d (140 g pure alcohol/week) or binge drinking
  2. Decision within 3 months of liver biopsy of suspected HCC nodule and non-tumour liver tissue performed as part of clinical routine
  3. No systemic treatment for HCC within 6 months prior to inclusion.
* Patients in the alcohol-related liver disease group without HCC:

  1. Alcohol consumption \> 30 g pure alcohol/d (or 210 g pure alcohol/week) for men and \> 20 g pure alcohol/d (140 g pure alcohol/week) or binge drinking
  2. Decision of less than 3 months for a liver biopsy to be performed as a clinical routine. Biopsy will be motivated by liver balance disturbance(s) and/or ultrasound steatosis given the lack of validated non-invasive tests or the lack of accuracy (grey areas) of available non-invasive tests for the diagnosis of necro-inflammation and/or fibrosis in some of these patients.

Exclusion Criteria:

1. Positive HIV serology
2. Patients with detectable hepatitis C viral load
3. Presence of Hbs antigen
4. History of autoimmune hepatitis type 1 or 2, primary biliary cholangitis, primary sclerosing cholangitis, Wilson's disease, genetic haemochromatosis homozygous, alpha1 anti-trypsin deficiency
5. Long-term use of methotrexate, corticosteroids, anti-Tumor Necrosis Factor cyclosporine, tacrolimus
6. History of solid organ transplantation or bone marrow transplantation
7. Cancerous disease in the process of being treated, except for skin cancer (excluding melanoma)
8. Patients under legal protection or unable to express their consent,
9. Pregnant or breastfeeding women

Where this trial is running

Nice

• Batiment Archimed 151, route de Saint Antoine de Ginestière — Nice, France (Recruiting)

Study contacts

• Study coordinator: Rodolphe Anty, MD, PhD

Conditions Non-Alcoholic Fatty Liver Disease; Non-Alcoholic Steatohepatitis; Alcohol-related Liver Disease; Cirrhosis, Liver; Hepatocellular Carcinoma