Understanding Gene ENvironment Interaction in ALcohol-related Hepatocellular Carcinoma

NCT ID: NCT07272200

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-01
• Study Completion Date: 2028-12-31

Brief Summary

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.

Conditions

HCC; Genetic Predisposition

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Risk factors

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)).

Group Type: EXPERIMENTAL

quantify of risk factors

Intervention Type: OTHER

the impact of risk factors and their interaction on the incidence of disease through a score that predicts HCC and select patients for whom screening is convenient.

Interventions

quantify of risk factors

the impact of risk factors and their interaction on the incidence of disease through a score that predicts HCC and select patients for whom screening is convenient.

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

OTHER

Sponsor Role: lead

Responsible Party

Serena Pelusi

Principal Investigator, Medical Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Istituto di Ricovero e Cura a Carattere Scientifico di natura pubblica

Milan, Milano, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Serena Pelusi

Role: CONTACT

serena.pelusi@policlinico.mi.it

02 5503 4192

Facility Contacts

Serena Pelusi

Role: primary

lserena.pelusi@policlinico.mi.it

02.5503.4192

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Genial

Identifier Type: -

Identifier Source: org_study_id