Understanding Gene ENvironment Interaction in ALcohol-related Hepatocellular Carcinoma

NCT07272200 | Recruiting

• 1 other identifier: Genial
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Impact of genetic risk factors

  The research aims to conduct the Measurement of the Frequency/Incidence (expressed as the percentage of the study population) of new genetic variants, identified using DNA Sequencing and subsequent bioinformatics analysis, that are associated with HCC in patients with ALD and related NAFLD. This measurement will be followed by the assessment of the CORRELATION between the newly identified genetic variants and the Prevalence (expressed as the percentage of the general population) of the clinical phenotype ALD-HCC.

  up to 60 months

Secondary Outcomes (1)

• Impact of genetic risk factor

  up to 60 months

Study Arms (1)

Risk factors

EXPERIMENTAL

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)).

Other: quantify of risk factors

Interventions

quantify of risk factors 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.

Risk factors

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead

Study Sites (1)

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

Milan, Milano, 20122, Italy

RECRUITING

MeSH Terms

Conditions

Genetic Predisposition to Disease

Condition Hierarchy (Ancestors)

Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Serena Pelusi

CONTACT

02 5503 4192; serena.pelusi@policlinico.mi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Medical Doctor

Study Record Dates

• First Submitted: February 18, 2025
• First Posted: December 9, 2025
• Study Start: December 1, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 9, 2025

Record last verified: 2025-02

Locations

IT (1)