Understanding Gene ENvironment Interaction in ALcohol-related Hepatocellular Carcinoma (GENIAL)

Institute of Hospitalization and Scientific Care (IRCCS)

Status: Enrolling

Conditions: Genetic Predisposition; HCC

Treatments: Other: quantify of risk factors

Study type: Interventional

Funder types: Other

Identifiers

NCT07272200

Genial

Details and patient eligibility

About

It has been estimated that alcohol causes around 40% of premature liver deaths in Europe each year, although this number is probably underestimated. Alcohol-related liver disease (ALD) is the most common cause of liver cirrhosis and liver death in Europe with a peak age of deaths occurring among individuals aged 40 to 50. Despite these findings, ALD is little studied with only 5% of all clinical trials in the field of liver disease recorded on ClinicalTrials.gov and only 5% of all publications in the same research area.

Liver cancer is the second most common cause of cancer-related death (15-20% survival at 5 years) and the second most common cause of alcohol-related cancers worldwide.

Like other complex diseases, ALD-HCC results from the interaction between environmental determinants and genetic variations but knowledge of gene-environment interactions is currently lacking in this area. The GENIAL project will address these needs through a comprehensive evaluation of gene-environment interactions concerning ALD-HCC.

Enrollment: 1,000 estimated patients

Sex: All

Ages: 45 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients from the EPIDEMIC (approval no. 1822 of 27 August 2013) and SERENA (last amendment no. 1151_2021 of 9 November 2021), already approved by the CE Milano Area 2 will be included.

• Diagnosis of NAFLD or cryptogenic liver disease, allowing a more liberal alcohol intake limit (<60/40 g/day in M/F), so that subjects with a moderate alcoholic component of the hepatopathy are also included, Important factor given the high epidemiological weight of this group
• Any of the following:
• Male patient with type 2 diabetes or obesity carrying at least three genetic variants in PNPLA3, TM6SF2, MBOAT7.
• Willingness to sign informed consent.

Exclusion criteria

• Alcohol intake >60/40 g/day in M/F
• Chronic viral or autoimmune hepatitis
• Any previously diagnosed liver genetic disease associated with increased risk of HCC (such as hereditary hemochromatosis, Wilson's disease, Alpha-1 antitrypsin deficiency)
• Use of drugs known to induce steatosis and liver disease
• HCC previously diagnosed the study start date.
• Other pathological conditions with prognosis less than two years.

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1,000 participants in 1 patient group

Risk factors

Experimental group

Description:

In the context of the study, data will be collected to characterize clinical risk factors: biopsy parameters, lifestyle and metabolic factors (BMI, abdominal circumference (CA), smoking, alcohol, diet, ongoing medical therapy), liver fat content and liver damage (by abdominal ultrasound and Fibroscan measurement of liver stiffness, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP)).

Treatment:

Other: quantify of risk factors