Liver Damage and Cardiometabolic Disorders in NAFLD

NCT ID: NCT04036357

Last Updated: 2019-08-16

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 2000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2036-12-31

Brief Summary

Liver fibrosis is the most important prognostic factor in patients with non-alcoholic factor disease. Clinical and biological condition, as diabetes or mutation for PNPLA3, are well known factors associated with liver fibrosis onset and progression. However, little is known about biochemical factors predicting liver fibrosis evolution in large NAFLD populations.

Detailed Description

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide. NAFLD includes a spectrum of diseases raging from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma.

The prevalence of NAFLD ranges from 20% in the general population to 80-90% in obese and/or diabetic patients. Type 2 diabetes is also associated with disease progression. Some genetic conditions are known to be related with NAFLD pathophysiology. Mutation of patatin like phospholipase domain containing 3 (PNPLA3) is the most frequent genetic disorder associated with NAFLD onset and its accelerated progression. Both type 2 diabetes and PNPL3 mutation are the better-known factors associated with liver fibrosis.

More than the amount of lipid accumulation in the hepatocytes or of liver inflammation, the most important prognostic factors in NAFLD is fibrosis, which can occur in all stage of NAFLD disease, also in simple steatosis without inflammation or ballooning. Advanced fibrosis (F stage ≥ 3) has been related not only with liver-related death but also with death from all causes.

In 2007 a noninvasive system, the NAFLD fibrosis score (NFS), was validated to identify NAFLD patients with advanced fibrosis. NFS ≥ 0.676 detects an advanced fibrosis (F3-F4) with a positive predictive value of 90%-82% while NFS ≤ -1.455 excludes advanced fibrosis with a negative predictive value of 93%-88%.

In addition, in different settings, a score named Fibrosis-4 (FIB-4) was also validated to detect advanced fibrosis in patients with hepatitis B virus and hepatitis C virus /human immunodeficiency virus coinfection. Fib-4 ≤ 1.45 excludes advanced fibrosis with a negative predictive value of 90%, while Fib-4 ≥ 3.25 detects advanced fibrosis with a positive predictive value of 65%.

Currently, little is known about biochemical and pharmacological factors predicting liver fibrosis evolution in large cohorts of NAFLD patients.

Therefore, the primary aim of the study Is to investigate biochemical and pharmacological factors associated with fibrosis progression, identified as variations in noninvasive fibrosis scores, in a large population of patients with ultrasonography diagnosis of fatty liver disease.

A growing number of evidences show a higher cardiovascular risk in patients with NAFLD. Most of the data are derived from diabetic patients and there are not data derived from ad hoc studies. In addition, there are only few data on factors predicting incident cardiovascular (CV) events in patients with NAFLD.

Therefore, the secondary objective of the study is to investigate the association between NAFLD and CV events and to detect factors predicting CV events inception.

Conditions

NAFLD; Liver Fibroses; Cardiovascular Diseases; Cardiovascular Risk Factor

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Patients aged 18 years old or more
• Patients with at least on of the following metabolic disorders

• Obesity
• Diabetes
• Arterial hypertension
• Dyslipidemia

Exclusion Criteria

• Average daily consumption of alcohol >20 g in women and of >30 g in men (assessed by Alcohol Use Disorders Identification Test, AUDIT;
• presence of hepatitis B surface antigen and antibody to hepatitis C virus;
• positive tests for autoimmune hepatitis;
• cirrhosis and other chronic liver diseases;
• diagnosis of oncological diseases
• concomitant therapy with drugs known to promote liver steatosis (e.g. amiodarone);
• other chronic infectious or autoimmune disease;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Roma La Sapienza

OTHER

Sponsor Role: lead

Responsible Party

Francesco Violi

Department Head

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maria Del Ben, MD

Role: STUDY_DIRECTOR

University of Roma La Sapienza

Daniele Pastori, MD

Role: PRINCIPAL_INVESTIGATOR

University of Roma La Sapienza

Francesco Baratta, MD

Role: PRINCIPAL_INVESTIGATOR

University of Roma La Sapienza

Francesco Angelico, MD

Role: PRINCIPAL_INVESTIGATOR

University of Roma La Sapienza

Locations

Day Service of Internal Medicine and Metabolic Disorders - Policlinico Umberto I - Sapienza University of Rome

Rome, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Francesco Baratta, MD, PI.

Role: CONTACT

francesco.baratta@uniroma1.it

+390649972249

Daniele Pastori, MD, PI.

Role: CONTACT

daniele.pastori@uniroma1.it

+390649972249

Facility Contacts

Maria Del Ben, MD

Role: primary

maria.delben@uniroma1.it

+390649972249

Francesco Baratta, MD

Role: backup

francesco.baratta@uniroma1.it

+390649972249

References

Baratta F, D'Erasmo L, Di Costanzo A, Umbro I, Pastori D, Angelico F, Del Ben M. Metabolic Syndrome but Not Fatty Liver-Associated Genetic Variants Correlates with Glomerular Renal Function Decline in Patients with Non-Alcoholic Fatty Liver Disease. Biomedicines. 2022 Mar 19;10(3):720. doi: 10.3390/biomedicines10030720.

Reference Type: DERIVED

PMID: 35327522 (View on PubMed)

Baratta F, Pastori D, Angelico F, Balla A, Paganini AM, Cocomello N, Ferro D, Violi F, Sanyal AJ, Del Ben M. Nonalcoholic Fatty Liver Disease and Fibrosis Associated With Increased Risk of Cardiovascular Events in a Prospective Study. Clin Gastroenterol Hepatol. 2020 Sep;18(10):2324-2331.e4. doi: 10.1016/j.cgh.2019.12.026. Epub 2019 Dec 27.

Reference Type: DERIVED

PMID: 31887443 (View on PubMed)

Other Identifiers

2277/2011

Identifier Type: -

Identifier Source: org_study_id