Liver Damage and Cardiometabolic Disorders in NAFLD
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: NAFLD, Liver Fibroses, Cardiovascular Diseases, Cardiovascular Risk Factor. Basic parameters: 18 years — 80 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Progression of LIver Damage and Cardiometabolic Disorders in Non-alcoholic Fatty Liver dIsease: an Observational Cohort STUDY. The Plinio Study
Overview
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.
Primary outcome measures
- Clinical, biochemical and genetic factors associated to progression of liver fibrosis in a large cohort of patients with NAFLD [Time frame: Patients will be followed for an expected mean time of 120 months]
Secondary outcome measures (12)
- The predictive role of non-invasive markers of fibrosis on the incidence of major cardiovascular events. [Time frame: Patients will be followed for an expected mean time of 60 months]
- Nutritional factors associated to NAFLD [Time frame: At Baseline]
- Platelet activation in NAFLD and NASH [Time frame: At Baseline]
- The predictive role of systemic markers of oxidative stress and antioxidant status on the incidence of cardiovascular events in NAFLD patients [Time frame: Patients will be followed for an expected mean time of 120 months]
- Factors associated with chronic kidney disease in NAFLD patients [Time frame: At Baseline]
- Predictors of kidney disease progression in patients with NAFLD [Time frame: Patients will be followed for an expected mean time of 60 months]
- Role of gut microbiota in NAFLD [Time frame: At Baseline]
- Echocardiographic changes in patients with NAFLD [Time frame: At Baseline]
- Score of cardiovascular risk in patients with NAFLD [Time frame: Patients will be followed for an expected mean time of 120 months]
- Dyslipidemia and cardiovascular events in patients with NAFLD [Time frame: Patients will be followed for an expected mean time of 120 months]
- Plasmatic and urinary isoprostanes [Time frame: At Baseline]
- Reactive species of oxygen in NAFLD and NASH [Time frame: At Baseline]
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;
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Italy · 1 center
- Day Service of Internal Medicine and Metabolic Disorders - Policlinico Umberto I - Sapienz — Rome
Publications
- Baratta F, Bartimoccia S, Pastori D, Cocomello N, Cammisotto V, Castellani V, Nocella C, Forte M, Picchio V, Carnevale R, Desideri G, Pignatelli P, Violi F. Neutrophil cathepsin G and risk of cardiovascular events in patients with diabetes mellitus. Cardiovasc Diabetol. 2025 Nov 26;24(1):448. doi: 10.1186/s12933-025-03005-y. PMID 41299502
- Baratta F, Cocomello N, Carpino G, Colantoni A, Cammisotto V, Bartimoccia S, Castellani V, Overi D, Lucatelli P, Ettorre E, Carnevale R, Pignatelli P, Pastori D, Del Ben M, Gaudio E, Desideri G, Violi F. Platelet Thromboxane B2 overproduction associated with liver fibrosis severity in patients with MASLD. Thromb Res. 2026 Jan;257:109540. doi: 10.1016/j.thromres.2025.109540. Epub 2025 Nov 15. PMID 41273899
- 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. PMID 35327522
- 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. PMID 31887443
Identifiers
NCT: NCT04036357 · 2277/2011