Clinical trial NCT03852238: Risk Factors of Hepatocellular Carcinomas Developed on Non-fibrotic Liver: Case-control Study (NoFlic Study)
Official title: Risk Factors of Hepatocellular Carcinomas Developed on Non-fibrotic Liver (NoFlic Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatocellular Carcinoma
Keywords: hepatocellular carcinoma
Non-cirrhotic liver
Risk factors
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
First posted: 2019-02-25
Enrollment: 283
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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.

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

Primary outcomes:
measure: exposure to Viral hepatitis B
timeFrame: Baseline
Secondary outcomes:
measure: exposure to viral hepatitis C
timeFrame: baseline
Other outcomes:
measure: exposure to Alcohol
timeFrame: baseline
measure: exposure to Exogenous female hormones
timeFrame: baseline
measure: history of liver pathology
timeFrame: baseline
measure: Family history of liver cancer
timeFrame: baseline
measure: Diabetes
timeFrame: baseline
measure: Dyslipidemias
timeFrame: baseline
measure: Medical treatments for dyslipidemia
timeFrame: baseline
measure: Metabolic syndrome
timeFrame: baseline
measure: Age of first menstruation
timeFrame: baseline
measure: Parity
timeFrame: baseline
measure: breastfeeding
timeFrame: baseline
measure: Menstrual status
timeFrame: baseline
measure: Duration of exposure to different variables
timeFrame: baseline
measure: fruits
timeFrame: baseline
measure: vegetables
timeFrame: baseline
measure: meat
timeFrame: baseline
measure: fish
timeFrame: baseline
measure: dairy products
timeFrame: baseline
measure: fats
timeFrame: baseline
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Bondy
country: France
facility: AP-HP Jean Verdier
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Caen
country: France
facility: CHU Caen
city: Clamart
country: France
facility: AP-HP Hopital Antoine Béclère
city: Clichy
country: France
facility: AP-HP Hopital Beaujon
city: Créteil
country: France
facility: CHI Créteil
city: Grenoble
country: France
facility: CHU Grenoble
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Lyon
country: France
facility: Hospices Civiles de Lyon
city: Paris
country: France
facility: AP-HP Cochin
city: Paris
country: France
facility: AP-HP Hopital Henri Mondor
city: Paris
country: France
facility: AP-HP Hopital Saint Antoine
city: Villejuif
country: France
facility: CHU Villejuif
Study officials:
References: