Genetic Predisposition, HCC
Conditions
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.
Interventions
OTHERquantify 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.
Sponsors
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Impact of genetic risk factors | 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
| Measure | Time frame | Description |
|---|---|---|
| Impact of genetic risk factor | 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. |
Countries
Italy
Contacts
Primary ContactSerena Pelusi
Outcome results
None listed