Hepatocellular Carcinoma in Patients With a Cirrhosis Due to an Alcoholic or a Non Alcoholic Fatty Liver Disease

Global prevalence of Non Alcoholic Fatty Liver Diseases (NAFLD) ranges from 22% to 28%.The spectrum of these hepatic abnormalities extends from isolated steatosis to steatohepatitis (Non Alcoholic Steato-Hepatitis, NASH) and steatofibrosis leading to cirrhosis and hepatocellular carcinoma. NAFLD is one of the main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma (developed in patients with or without cirrhosis). Despite this major public health concern, apart from lifestyle changes, treatment of NAFLD is still elusive as there is lack of efficacious pharmacological treatment. Alcoholic liver diseases are also frequent in Western countries. Alcoholic liver diseases and NAFLD share common pathological lesions and molecular pathways. This is illustrated by the emerging role of abnormalities of the microbiota (dysbiosis) in these 2 diseases leading to the concept of " liver-gut axis ". Whereas the molecular mechanisms responsible for the progression from a "safety" state to NASH or to a severe alcoholic steato-hepatitis are still unclear, hepatic inflammation is a key factor involved in the progression of NAFLD and alcoholic liver disease.

The hypothesis is that cellular and molecular abnormalities and gut dysbiosis could be present in patients with simple steatosis or with steato-hepatitis and could be responsible for the occurrence of hepatocellular carcinoma particularly without cirrhosis.

The main objective is to compare cellular and inflammatory pathways in liver with and without hepatocellular carcinoma in patients with alcoholic or non-alcoholic fatty liver diseases.


Eligibility Criteria:
Group 1

Inclusion Criteria :

* Available social insurance
* Signed consent for the study enrollment
* Age ≥ 18 years

Exclusion Criteria :

* Patients in the group with metabolic fatty liver with hepatocellular carcinoma
* Alcohol consumption ≤ 30 g/d (or 210 g/week) in men and ≤ 20 g/d (or 140 g/week) in women.
* Decision (less than 3 months) to perform a liver biopsy of a tumor suspect of HCC and of adjacent liver in routine practice.
* No systemic HCC treatment in the previous 6 months

Group 2

Inclusion Criteria :

* Available social insurance
* Signed consent for the study enrollment
* Age ≥ 18 years

Exclusion Criteria :

* Patients in the group with metabolic fatty liver without hepatocellular carcinoma
* Alcohol consumption ≤ 30 g/d (or 210 g/week) in men and ≤ 20 g/d (or 140 g/week) in women.
* Decision (less than 3 months) to perform a liver biopsy in routine practice. Liver biopsy will be organized because of one or more liver abnormalities and/or fatty liver seen at liver ultrasound due to the current lack of validated non-invasive marker of inflammation, cellular death and fibrosis in these patients.

Group 3

Inclusion Criteria :

* Available social insurance
* Signed consent for the study enrollment
* Age ≥ 18 years

Exclusion Criteria :

* Patients with an alcoholic liver disease with hepatocellular carcinoma
* Alcohol consumption \> 30 g/d (or 210 g/week) in men and \> 20 g/d (or 140 g/week) in women.
* Decision (less than 3 months) to perform a liver biopsy of a tumor suspect of HCC and of adjacent liver in routine practice.
* No systemic HCC treatment in the previous 6 months

Group 4

Inclusion Criteria :

* Available social insurance
* Signed consent for the study enrollment
* Age ≥ 18 years

Exclusion Criteria :

* Patients with an alcoholic liver disease without hepatocellular carcinoma
* Alcohol consumption \> 30 g/d (or 210 g/week) in men and \> 20 g/d (or 140 g/week) in women.
* Decision (less than 3 months) to perform a liver biopsy in routine practice. No systemic HCC treatment in the previous 6 months. Liver biopsy will be organized because of one or more liver abnormalities and/or fatty liver seen at liver ultrasound due to the current lack of validated non-invasive marker of inflammation, cellular death and fibrosis in these patients.