Risk Factors of Hepatocellular Carcinomas Developed on Non-fibrotic Liver: Case-control Study (NoFlic Study)

Study Overview
=================
Brief Summary
-----------------
The main objective of this study is to identify direct carcinogenic factors in the absence of cirrhosis, and the carcinogenesis pathways involved on nonfibrotic liver (NfCHC).

Detailed Description
-----------------
Most hepatocellular carcinoma (HCC) complicates cirrhosis, which is often caused by infection with hepatitis B or C viruses, alcohol, obesity, exposure to aflatoxin B1 (AFB1) or hemochromatosis. Nevertheless, 10 to 40% of HCCs can develop on non-cirrhotic terrain and about 5% on nonfibrotic liver (NfHCC). In 20 to 40% of these NfHCCs, no classical HCC risk factor is identified. Some cases could be the result of a transformation of an adenoma. Others may be associated with yet non-formally identified toxins and / or a specific genetic predisposition. While there is a lot of data on alterations of signaling pathways (ß-catenin, AKT / mTOR, Ras / pERK, etc.) in classical HCCs, altered pathways remain unknown in most NfHCCs, even in some cases, activation of β-catenin, inactivating mutations of HNF1 or activators of gp130 have been shown. A specific study of NfHCCs, rather rare cancers, represents an opportunity to look for directly carcinogenic factors in the absence of cirrhosis, and to dissect the involved carcinogenesis pathways.

Official Title
-----------------
Risk Factors of Hepatocellular Carcinomas Developed on Non-fibrotic Liver (NoFlic Study)

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Other: Blood test and self-administrated questionnaires


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: CASES: patients aged 18 years and older with a diagnosis of NfHCC with anatomopathological examination and showing a HCC according to standard histopathological criteria and an absence of significant fibrosis in non-tumoral tissues with the METAVIR system score or equivalent (F0 or F1) or the Kleiner et al stage of ASH and NASH (≤stade 2); signed informed consent; affiliated or beneficiary of a social security system CONTROLS: patients aged 18 years and older without NfHCC at baseline; patients for whom an endoscopy is programmed as part of an assessment of intestinal functional disorders, dyspeptic disorders or screening colonoscopy or hospitalized patients in orthopedic surgery / traumatology or rheumatology departments; signed informed consent; affiliated or beneficiary of a social security system Exclusion Criteria: CASES: HCC diagnosed without pathological examination; hepatic transplantation before the diagnosis of HCC; patients unable to answer questions; patients who do not speak French or live abroad. CONTROLS: History of liver cancer; other cancers under treatment except cutaneous cancers; Colonoscopy indicated in case of familial form of colon cancer; patient with cirrhosis; patients unable to answer questions; patients who do not speak French or live abroad; Relationship or same home with the case

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases: patients with hepatocellular carcinoma on non-cirrhotic<br>Blood test and self-administrated questionnaires (medical history of the participant and his / her family, tobacco consumption, alcoholic and non-alcoholic beverages consumption, eating habits, type of employment and exposure, stays abroad longer than 1 month | |
| Control: patients without hepatocellular carcinoma<br>Blood test and self-administrated questionnaires (medical history of the participant and his / her family, tobacco consumption, alcoholic and non-alcoholic beverages consumption, eating habits, type of employment and exposure, stays abroad longer than 1 month | Other: Blood test and self-administrated questionnaires<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| exposure to Viral hepatitis B | binary yes / undiagnosed by positive serology for anti-HBc antibodies isolated or associated with positive serology for anti-HBs antibodies | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| exposure to viral hepatitis C | binary yes / undiagnosed by positive serology for positive anti-HCV antibodies | baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hepatocellular carcinoma, Non-cirrhotic liver, Risk factors