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

Completed

• Conditions: Hepatocellular Carcinoma
• Interventions: Other: Blood test and self-administrated questionnaires

• Registration Number: NCT03852238
• Lead Sponsor: University Hospital, Bordeaux

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.

Study Timeline

• Study Start: 2010-08-18
• Primary Completion: 2013-11-14
• Study Completion: 2013-11-14
• Status Verified: 2019-01
• Study First Submitted: 2019-01-31
• Study First Submitted QC: 2019-02-21
• Last Update Submitted: 2019-02-21
• Study First Posted: 2019-02-25
• Last Update Posted: 2019-02-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 283

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control: patients without hepatocellular carcinoma	Blood test and self-administrated questionnaires	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

Primary Outcome Measures

Name	Time	Method
exposure to Viral hepatitis B	Baseline	binary yes / undiagnosed by positive serology for anti-HBc antibodies isolated or associated with positive serology for anti-HBs antibodies

Secondary Outcome Measures

Name	Time	Method
exposure to viral hepatitis C	baseline	binary yes / undiagnosed by positive serology for positive anti-HCV antibodies

Trial Locations

Locations (14)

CHU Amiens; 🇫🇷 Amiens, France

AP-HP Jean Verdier; 🇫🇷 Bondy, France

CHU Bordeaux; 🇫🇷 Bordeaux, France

CHU Caen; 🇫🇷 Caen, France

AP-HP Hopital Antoine Béclère; 🇫🇷 Clamart, France

AP-HP Hopital Beaujon; 🇫🇷 Clichy, France

CHI Créteil; 🇫🇷 Créteil, France

CHU Grenoble; 🇫🇷 Grenoble, France

AP-HP Hopital Saint Antoine; 🇫🇷 Paris, France

Hopital Edouard Herriot; 🇫🇷 Lyon, France

Hospices Civiles de Lyon; 🇫🇷 Lyon, France

AP-HP Cochin; 🇫🇷 Paris, France

AP-HP Hopital Henri Mondor; 🇫🇷 Paris, France

CHU Villejuif; 🇫🇷 Villejuif, France