From the Guidelines
The main metabolic source of free fatty acids (FFAs) in non-alcoholic fatty liver disease (NAFLD) pathogenesis, apart from diet, is adipose tissue lipolysis, and the main cause of mortality in NAFLD is cardiovascular disease (CVD). The pathogenesis of NAFLD involves the accumulation of excess fat in the liver, which is contributed by the increased release of FFAs from adipose tissue lipolysis, as seen in insulin resistance states 1. Key points to consider in NAFLD pathogenesis include:
- Insulin resistance leading to impaired suppression of lipolysis in adipose tissue
- Increased release of FFAs into the bloodstream
- Uptake of FFAs by the liver, contributing to hepatic fat accumulation and liver damage The main cause of mortality in NAFLD is CVD, which is attributed to the shared risk factors between NAFLD and CVD, including insulin resistance, dyslipidemia, and metabolic syndrome 1. Important considerations for NAFLD-related mortality include:
- Systemic inflammatory state and metabolic dysregulation associated with NAFLD
- Accelerated atherosclerosis and increased cardiovascular events
- CVD being the leading cause of death in patients with NAFLD, followed by extrahepatic malignancies and liver-related complications 1.
From the Research
NAFLD Pathogenesis and Metabolic Source of FFAs
- The main metabolic source of free fatty acids (FFAs) other than diet is adipose tissue lipolysis, as experimentally creating high FFA concentrations can reproduce the metabolic abnormalities of obesity in lean, healthy persons 2.
- Adipose tissue dysfunction is causally linked to NAFLD since it causes intrahepatic triglyceride (IHTG) accumulation through increased hepatic lipid flow, due to insulin resistance and pro-inflammatory adipokines release 3.
Main Cause of Mortality in NAFLD
- The leading causes of death in people with NAFLD are cardiovascular disease and extrahepatic malignancy, although advanced liver fibrosis is a key prognostic marker for liver-related outcomes and overall mortality 4.
- Patients with cirrhosis should be screened for hepatocellular carcinoma and oesophageal varices, highlighting the importance of monitoring and managing liver-related complications in NAFLD patients 4.