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

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

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).

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Other: Blood test and self-administrated questionnaires

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 Type: Observational
• Enrollment (Actual): 283

Contacts and Locations

Study Locations

• France
  • Amiens, France
    • CHU Amiens
  • Bondy, France
    • AP-HP Jean Verdier
  • Bordeaux, France
    • CHU Bordeaux
  • Caen, France
    • CHU Caen
  • Clamart, France
    • AP-HP Hôpital Antoine Beclere
  • Clichy, France
    • AP-HP Hôpital Beaujon
  • Créteil, France
    • CHI Créteil
  • Grenoble, France
    • CHU Grenoble
  • Lyon, France
    • Hôpital Edouard Herriot
  • Lyon, France
    • Hospices Civiles de Lyon
  • Paris, France
    • AP-HP Cochin
  • Paris, France
    • AP-HP Hopital Saint Antoine
  • Paris, France
    • AP-HP Hôpital Henri Mondor
  • Villejuif, France
    • CHU Villejuif

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

CASES: patients 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)

- CONTROLS: patients without NfHCC at baseline

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases: patients with hepatocellular carcinoma on non-cirrhotic; 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; 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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
exposure to Alcohol	binary variable, separating large consumers from others	baseline
exposure to Exogenous female hormones	oral contraceptive coded as a binary variable	baseline
history of liver pathology	binary variable: yes/no	baseline
Family history of liver cancer	binary variable: yes/no	baseline
Diabetes	categorical variable (depending on the type of diabetes: 1 or 2).	baseline
Dyslipidemias	qualitative variables: hypercholesterolemia / hyper triglyceridemia	baseline
Medical treatments for dyslipidemia	depending on the type of medication: statins, fibrates, other	baseline
Metabolic syndrome	binary variable: present / absent	baseline
Age of first menstruation	quantitative variable in years	baseline
Parity	number of children	baseline
breastfeeding	binary variable : yes / no	baseline
Menstrual status	menopausal status will be treated as a binary variable	baseline
Duration of exposure to different variables	quantitative variable in months	baseline
fruits	frequency of intake assessed by a frequency food questionnaire	baseline
vegetables	frequency of intake assessed by a frequency food questionnaire	baseline
meat	frequency of intake assessed by a frequency food questionnaire	baseline
fish	frequency of intake assessed by a frequency food questionnaire	baseline
dairy products	frequency of intake assessed by a frequency food questionnaire	baseline
fats	frequency of intake assessed by a frequency food questionnaire	baseline

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: National Cancer Institute, France

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2010
• Primary Completion (Actual): November 14, 2013
• Study Completion (Actual): November 14, 2013

Study Registration Dates

• First Submitted: January 31, 2019
• First Submitted That Met QC Criteria: February 21, 2019
• First Posted (Actual): February 25, 2019

Study Record Updates

• Last Update Posted (Actual): February 25, 2019
• Last Update Submitted That Met QC Criteria: February 21, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; Risk factors; Non-cirrhotic liver
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: CHUBX 2010/03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No