Defining the genomic landscape of MASLD
DEFINIZIONE DEL PANORAMA GENOMICO DELLA MASLD (DEFINING THE GENOMIC LANDSCAPE OF METABOLIC STEATOTIC LIVER DISEASE)
This project will analyze germline and somatic genetic variants in 40–70-year-olds with advanced MASLD and in high-risk overweight/obese blood donor controls to see which variants are linked to progression to advanced fibrosis and liver cancer.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 2880 (estimated) |
| Ages | 18 Years to 90 Years |
| Sex | All |
| Sponsor | Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico Academic / other |
| Locations | 1 site (Milan, Milano) |
| Trial ID | NCT07249112 on ClinicalTrials.gov |
What this trial studies
This single-center effort collects liver tissue (biopsies or cholecystectomies) and blood from patients aged 40–70 with advanced MASLD (fibrosis ≥2 or HCC) and from overweight/obese control blood donors with cardiometabolic risk factors. Researchers will perform germline and somatic genomic profiling to identify variants associated with progression to advanced fibrosis and hepatocellular carcinoma. Participants may be enrolled from the SERENA or REASON cohorts and the Liver Bible blood donor group. The goal is to map genetic differences between progressors and controls to generate biomarkers and hypotheses for future targeted interventions.
Who should consider this trial
Good fit: Ideal candidates are 40–70-year-olds with advanced MASLD (liver fibrosis ≥2 or HCC) enrolled in SERENA/REASON or overweight/obese blood donors aged 40–70 with at least two cardiometabolic risk factors.
Not a fit: Patients with other chronic liver diseases (for example positive HCV-RNA or HBsAg), those outside the 40–70 age range, or those without available tissue or consent are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, the project could identify genetic markers that predict who is at higher risk of progressing to advanced fibrosis or HCC, enabling better monitoring and personalized care.
How similar studies have performed: Previous genetic studies have identified common risk variants (e.g., PNPLA3, TM6SF2, MBOAT7) but a comprehensive germline and somatic genomic map specifically linking variants to progression and HCC remains incompletely characterized.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: Specific Inclusion Criteria for Patients with Advanced MASLD: * Patients with advanced MASLD defined as liver fibrosis ≥2 and/or the development of HCC (Hepatocellular Carcinoma); * Patients enrolled in the context of the SERENA study and, where applicable, also in the context of the REASON study; * Liver biopsy for suspected Non-Alcoholic Steatohepatitis (NASH) at the time of diagnosis; * Cholecystectomies; * Age \[40-70 years\]; * Patients who have signed the informed consent form. Specific Inclusion Criteria for the Control Group: Blood donors participating in the Liver Bible study aged between 40 and 70 years who are overweight or obese and have at least two of the following risk factors: * Impaired fasting glucose or Diabetes Mellitus * Dyslipidemia * Arterial hypertension. Exclusion Criteria: Specific exclusion Criteria for Patients with Advanced MASLD: * Positivity for chronic viral hepatitis (HCV-RNA and/or HBsAg); * Positivity for other liver diseases such as autoimmune and viral hepatitis (Hepatitis B and C), hereditary hemochromatosis, alpha-1-antitrypsin deficiency, or Wilson's disease. Specific Exclusion Criteria for the Control Group: Subjects with chronic degenerative diseases will be excluded, with the exception of well-controlled hypertension and Type 2 Diabetes Mellitus that does not require pharmacological therapy (as is already standard practice for blood donation eligibility). Also excluded are donors aged \> 65 and \< 40 years.
Where this trial is running
Milan, Milano
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Istituto di Ricovero e Cura a Carattere Scientifico di natura pubblica — Milan, Milano, Italy (Recruiting)
Study contacts
- Study coordinator: Luca Vittorio Carlo Valenti, Doctor
- Email: luca.valenti@policlinico.mi.it
- Phone: 02 5503 6595
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.