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NCT Number: NCT07272200

Understanding Gene ENvironment Interaction in ALcohol-related Hepatocellular Carcinoma

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.

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Key information

Conditions

HCC Disease Attributes Disease Susceptibility Genetic Predisposition Genetic Predisposition to Disease Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

45 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

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

Milan, Milano, 20122, Italy

Location status: Recruiting

Location contact

Serena Pelusi

CONTACT

[email protected]

02.5503.4192

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Primary outcomes

  1. Impact of genetic risk factors

    Time frame: up to 60 months

    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.

Secondary outcomes

  1. Impact of genetic risk factor

    Time frame: up to 60 months

    The primary goal is the assessment of the Predictive Capacity (measured via Area Under the Receiver Operating Characteristic Curve (AUC) and P-value) of a newly created Polygenic-Clinical Risk Score (PRS-C) for the development of HCC. Subsequently, the Predictive Accuracy (measured in percentage of correct predictions, Sensitivity, and Specificity) of an Artificial Intelligence (AI) Algorithm will be evaluated. This Algorithm will be trained by integrating the aforementioned PRS (derived from the combination of genetic and non-genetic information) and other clinical and demographic variables, aiming to obtain predictive information on the individual risk of developing the disease.

Study contacts

Contact information is provided by the study sponsor or research team.

Serena Pelusi

CONTACT

[email protected]

02 5503 4192

Sponsors and collaborators

Lead sponsor

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Other

Registry information

Acronym: GENIAL

Important dates

Study start
2023
Primary completion
2026
Study completion
2028
First posted
Dec 9, 2025
Registry last updated
Dec 9, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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