Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. To date, NAFLD is the most frequent chronic liver disease seen day by day in clinical practice across most high-income countries, affecting nearly 25–30% of adults in the general population and up to 70% of patients with T2DM. Over the last few decades, it clearly emerged that NAFLD is a “multisystemic disease” and that the leading cause of death among patients with NAFLD is cardiovascular disease (CVD). Indeed, several observational studies and some meta-analyses have documented that NAFLD, especially its advanced forms, is strongly associated with fatal and non-fatal cardiovascular events, as well as with specific cardiac complications, including sub-clinical myocardial alteration and dysfunction, heart valve diseases and cardiac arrhythmias. Importantly, across various studies, these associations remained significant after adjustment for established cardiovascular risk factors and other confounders. Additionally, several observational studies and some meta-analyses have also reported that NAFLD is independently associated with specific microvascular conditions, such as chronic kidney disease and distal or autonomic neuropathy. Conversely, data regarding a potential association between NAFLD and retinopathy are scarce and often conflicting. This narrative review will describe the current evidence about the association between NAFLD and the risk of macro- and microvascular manifestations of CVD, especially in patients with T2DM. We will also briefly discuss the biological mechanisms underpinning the association between NAFLD and its advanced forms and macro- and microvascular CVD.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease, which classically includes a spectrum of progressive pathological conditions, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) with different grades of fibrosis and cirrhosis (Figure 1) [1,2]
NAFLD was associated with an increased risk of all-cause mortality, but not with an increased risk of cardiovascular disease (CVD)
NAFLD was associated with an increased risk of myocardial infarction, ischemic stroke, atrial fibrillation, and heart failure
Summary
Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease, which classically includes a spectrum of progressive pathological conditions, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) with different grades of fibrosis and cirrhosis (Figure 1) [1,2]. Several observational studies and some meta-analyses have reported that NAFLD, as detected by indirect biomarkers of steatosis, ultrasonography or liver biopsy, is associated with an increased risk of prevalent and incident chronic kidney disease (CKD) in patients with and without T2DM, independent of established cardio-metabolic risk factors, diabetesrelated variables and other potential confounders [28,30]. In a cross-sectional study including 157 Italian patients with T2DM, who underwent liver ultrasonography and kidney function assessment, our research group reported that the presence of the G allele of rs738409 in the PNPLA3 gene was associated with an increased risk of CKD (defined as
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