The Liver BIoBank Lombardia of Fatty Liver

NCT ID: NCT06566105

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 2500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2037-12-31

Brief Summary

NAFLD is most frequently linked to excess adiposity, insulin resistance and cardiometabolic risk factors, it has become the leading cause of liver disease worldwide, and is associated with increased mortality due to multiple causes. HFC has a strong genetic component and the investigators recently showed that it plays a causal role in determining progressive liver disease and insulin resistance.

The genetic risk score predicting liver fat content (HFC-GRS) improves the stratification of liver related events, and the investigators have preliminary data on new common and rare variants that contribute to NAFLD susceptibility, and on a new non-invasive circulating biomarker associated with hepatic fat and lipotoxicity (Interleukin-32). However, no data are yet available on the causal role of hepatic fat on the procoagulant state associated with NAFLD, which could participate to liver damage and is a causal factor in atherothrombotic complications. The aim of the study is to examine the potential application of a precision medicine approach to the improvement of stratification of the risk of liver-related and cardiovascular thrombotic complications of hepatic fat accumulation (HFC) and non-alcoholic fatty liver disease (NAFLD), with a special focus on the role of procoagulant imbalance in mediating the at-risk phenotypes.

Detailed Description

The aims of the project will be:

• To examine whether a comprehensive HFC-GRS coupled with evaluation of environmental triggers, imaging techniques and novel circulating biomarkers help in stratifying of the risk of NAFLD and associated complications in a cohort of asymptomatic individuals at high risk from the general population (the Liver-Bible cohort). The Liver-Bible cohort is made up of >2,500 individuals with multiple metabolic risk factors, who are undergoing a comprehensive evaluation of environmental exposure, HFC and liver stiffness measurement, liver histology in those at risk of advanced fibrosis, circulating biomarkers of hepatic damage, coagulation status and early cardiovascular damage;
• To validate the causal role of HFC in the alterations of metabolism, coagulation, and early cardiovascular damage associated with NAFLD;
• To identify new inherited risk variants and microbiota profiles associated with NAFLD; to investigate the mechanism linking genetic susceptibility with liver disease and coagulation balance in in vitro models of NAFLD in hepatocytes, sinusoidal endothelial cells, and hepatic stellate cells. The investigators expect to demonstrate that the combined evaluation of genetic and novel circulating biomarkers with imaging improves the non-invasive prediction of both liver-related (leading to personalised and cost-effective surveillance of liver-related complications) and unrelated complications of NAFLD in at risk individuals, with a special focus on the role of the coagulation balance, and to pinpoint new genetic modifiers of disease progression that may be prioritized for future therapeutic approaches.

Conditions

NAFLD; Precision Medicine; Cardiovascular Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

PROCEDURES RELATED TO THE STUDY

• Selection of blood donors at risk of NAFLD and metabolic diseases and sample collection blood
• Evaluation of early cardiovascular damage and characterization of liver damage in patients with high probability of severe NAFLD
• Study of genomics and biomarkers
• Generation of an in vitro genetic model of NAFLD

Group Type: OTHER

precision medicine approach

Intervention Type: GENETIC

precision medicine approach to improvement of risk stratification of hepatic and cardiovascular complications in non-alcoholic fatty liver disease in a group of healthy subjects at increased risk of metabolic pathologies

Interventions

precision medicine approach

precision medicine approach to improvement of risk stratification of hepatic and cardiovascular complications in non-alcoholic fatty liver disease in a group of healthy subjects at increased risk of metabolic pathologies

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Blood donors aged between 40 and 65 years presence of clinical diagnosis of overweight or obesity (body mass index-BMI > 25 kg/m2),
• increased fasting blood glucose or T2D (fasting blood glucose ≥100mg/dl) or dyslipidemia (triglycerides≥150mg/dl, HDL<45/55 in M/F) or arterial hypertension (n = 2,452, 11.8% of the entire cohort).

Exclusion Criteria

• subjects suffering from chronic degenerative diseases, except hypertension in good compensation and diabetes type 2 mellitus which does not require pharmacological therapy (as is already common practice for eligibility for donation of blood)
• donors aged > 65 and < 40 to avoid the introduction of bias

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

OTHER

Sponsor Role: lead

Responsible Party

Luca Valenti:

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Istituto di Ricovero e Cura a Carattere Scientifico di natura pubblica

Milan, Milano, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Luca Vittorio Carlo Valenti

Role: CONTACT

luca.valenti@policlinico.mi.it

02 5503 6595 ext. 56595

Facility Contacts

Luca Vittorio Carlo Valenti

Role: primary

luca.valenti@policlinico.mi.it

02 5503 6595 ext. 56595

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

LIVER BIBLE

Identifier Type: -

Identifier Source: org_study_id