HCCGENIALNCT07272200
Understanding Gene ENvironment Interaction in ALcohol-related Hepatocellular Carcinoma
A study testing quantify of risk factors in people with HCC and Genetic Predisposition, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 to 75 years
- Conditions the study is for
- HCC, Genetic Predisposition
- What is being tested?
- quantify of risk factors
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,000 participants
- Where
- 1 siteItaly
- Study dates
- 1 Dec 2023to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients from the EPIDEMIC (approval no. 1822 of 27 August 2013) and SERENA (last amendment no. 11512021 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Istituto di Ricovero e Cura a Carattere Scientifico di natura pubblica
Milan, Milano, 20122
Serena Pelusi, 02.5503.4192, lserena.pelusi@policlinico.mi.it
About this study
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
- Being tested
- quantify of risk factors
- Medical subject headings
- Genetic Predisposition to Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
quantify of risk factorsOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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)). Receives: Other: quantify of risk factors |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 60 months
Secondary outcomes (1)
Impact of genetic risk factor
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.
Measured: up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2025
- Study start1 Dec 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HCCStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Serena Pelusi, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07272200
- Sponsor's protocol ID
- Genial
- Acronym
- GENIAL
- Status last verified
- Feb 2025
- First submitted
- 18 Feb 2025
- Last updated
- 9 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding Gene ENvironment Interaction in ALcohol-related Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT07272200
- Acronym / sponsor ID
- GENIAL / Genial
- Conditions
- HCC, Genetic Predisposition
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Study start
- 1 Dec 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 9 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Risk factors | Experimental | Other: quantify of risk factorsIn 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)). |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients from the EPIDEMIC (approval no. 1822 of 27 August 2013) and SERENA (last amendment no. 11512021 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| quantify of risk factorsthe 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. | Other | Risk factors |
Primary outcome
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.
1 secondary outcome
Impact of genetic risk factor
Time frame: up to 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing quantify of risk factors in people with HCC and Genetic Predisposition, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Serena Pelusi (02 5503 4192, serena.pelusi@policlinico.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Impact of genetic risk factors (time frame: up to 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2025.