CHronic Hepatopathies Associated With ALcohol Consumption aNd metAbolic Syndrome

CHronic Hepatopathies Associated With ALcohol Consumption aNd metAbolic Syndrome

The aim is to determine the metabolic factors, host immune factors, and medical imaging data associated with the development of HepatoCellular Carcinoma (HCC) in patients with alcohol-related liver disease or dysmetabolic steatosis/Non-Alcoholic SteatoHepatitis.

The investigators will include patients with and without cirrhosis in order to identify early molecular mechanisms involved in the development of HCC especially in non-cirrhotic patients.

Type and methodology of the research:

Within the framework of the usual management of the patient's pathology, a clinico-biological characterization (dietary and physical activity questionnaires, "performans status", anthropometric measurements, usual blood biology characterizing the hepatic, renal and inflammatory function, the carbohydrate and lipid metabolism, the non invasive test for liver fibrosis ELF etc.) will be carry out. In order to collect radiomic data, liver imaging (particularly in case of HCC) will be done.

A liver biopsy and constitution of a biobank (samples of plasma, sera, DNA and leucocyte pellets) will be performed.

The elements necessary for the classification of possible hepatocellular carcinomas (BCLC classification) will be collected.

Anticipated research schedule:

• The duration of inclusion in this research will be 10 years.
• The duration of the patient's participation will be from 1 day (if the consent is signed and the biopsy is performed on the same day) to 2 months (maximum reflection period is 8 weeks between the signature of the consent and the taking of samples).
• The total duration of the research (from the first inclusion, to the last visit of the last participant) will be 10 years and 2 months.

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