liver damage and cardiometabolic disorders in nafld

Conditions: NAFLD; Liver Fibroses; Cardiovascular Diseases; Cardiovascular Risk Factor

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.

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.

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;

Keywords: nafld liver fibrosis cardiovascular