NCT07249112Completed
DEFINITION OF THE GENOMIC LANDSCAPE OF MASLD
DEFINIZIONE DEL PANORAMA GENOMICO DELLA MASLD (DEFINING THE GENOMIC LANDSCAPE OF METABOLIC STEATOTIC LIVER DISEASE)
Source: ClinicalTrials.gov · Last updated 4 Nov 2026
Brief summary (registry, in English)
The Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a leading cause of chronic liver disease globally, with a prevalence exceeding 30% in the population. MASLD is strictly associated with insulin resistance and cardiometabolic conditions, and in 20-30% of cases, it can progress to steatohepatitis (MASH), which is characterized by progressive liver damage and inflammation. In patients at higher risk, the disease can lead to the onset of advanced fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). One of the main problems in the clinical management of MASLD is the absence of specific risk biomarkers and the lack of effective treatments, especially for patients with advanced-stage disease. MASLD has a well-documented and enormous genetic component, with studies having identified several common variants associated with this pathology, such as those in the PNPLA3, TM6SF2, and MBOAT7 genes. However, these variants identified so far only explain a small part of MASLD's heritability, suggesting the contribution of rare loss-of-function (LoF) variants as well. Furthermore, scientific evidence indicates that the accumulation of somatic variants, both in hepatocytes and myeloid cells, could also play a key role in MASLD progression. In particular, clonal hematopoiesis of indeterminate potential (CHIP), which is a condition characterized by the presence of hematopoietic clones with somatic mutations often associated with leukemia and cardiovascular diseases, might favor the onset of hepatocellular carcinoma. However, the evidence available to date is still limited and requires further investigation and studies on larger cohorts. The current study therefore aims to deepen this aspect through the analysis of the genetic profile using a Whole-Genome Sequencing (WGS) approach. DNA samples from peripheral blood from patients with advanced MASLD and peripheral blood DNA samples from controls presenting various associated metabolic risk factors will be sequenced. In addition, 80 liver tissue samples from patients with advanced MASLD will also be sequenced to identify specific somatic mutations. The expected results from this study include the identification of new genetic variants associated with MASLD progression, the improvement of risk stratification through the development of polygenic risk scores, and the identification of potential therapeutic targets. This study represents a fundamental step for understanding the biology of MASLD and could have important clinical implications for disease management.
- Status (registry)
- Completed
- Study type
- Interventional
- Enrollment
- 2880 (actual)
- First submitted
- 17 Nov 2025
- Start date
- 1 Sept 2025
- Primary completion date
- 31 Jul 2026
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
- Diseases
- Fatty liver disease (MASLD/MASH)
- NCT number
- NCT07249112
What you commit to
- Study type: Interventional
- Participants enrolled: 2880
- From 1 Sept 2025 to the primary completion date, 31 Jul 2026
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Other illness
- Positivity for chronic viral hepatitis (HCV-RNA and/or HBsAg);
Age
- 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.
Other
- Specific exclusion Criteria for Patients with Advanced MASLD:
Who the study is looking for
- 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.
Age in the registry: 18 years to 90 years · Sex: All · Accepts healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Istituto di Ricovero e Cura a Carattere Scientifico di natura pubblica Coordinator of this site? Confirm its status | Milan | Italy | Unknown status |
This page is information, not medical advice. Discuss any trial with your doctor.