Understanding Gene ENvironment Interaction in ALcohol-related Hepatocellular Carcinoma

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.

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.