The Liver BIoBank Lombardia of Fatty Liver

Institute of Hospitalization and Scientific Care (IRCCS)

Status: Enrolling

Conditions: Cardiovascular Diseases; NAFLD; Precision Medicine

Treatments: Genetic: precision medicine approach

Study type: Interventional

Funder types: Other

Identifiers

NCT06566105

LIVER BIBLE

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,500 estimated patients

Sex: All

Ages: 40 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2,500 participants in 1 patient group

PROCEDURES RELATED TO THE STUDY

Other group

Description:

* 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

Treatment:

Genetic: precision medicine approach