Pathophysiology and Risk Factors of Fatty Liver Disease

Lipid Acquisition

Hepatic steatosis represents the histologic hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD) and is characterized by the accumulation of lipid droplets in the cytoplasm of liver cells, according to the Clinical Gastroenterology and Hepatology 5, 6
The American Association for the Study of Liver Diseases defines hepatic steatosis as the abnormal accumulation of triglycerides within hepatocytes, defined as intrahepatic fat comprising at least 5% of liver weight 7

The accumulation of hepatic triglycerides results from multiple interconnected metabolic derangements, including enhanced influx of free fatty acids from adipose tissue lipolysis and chylomicrons from intestinal absorption directly to the liver, as reported by Clinical and Molecular Hepatology 8
Insulin resistance serves as the central metabolic driver linking adipose tissue dysfunction to hepatic fat accumulation, according to Praxis Medical Insights 7

The European Association for the Study of the Liver states that hepatic steatosis exists along a clinical spectrum with vastly different prognostic implications, with simple steatosis representing 70-75% of all MASLD cases and steatohepatitis occurring in 25-30% of MASLD cases 9, 7
The American College of Gastroenterology recommends that steatohepatitis be recognized as a critical pathophysiologic transition characterized by ≥5% hepatic steatosis plus inflammation with hepatocyte injury, with or without fibrosis 9, 7

The World Health Organization reports that MASLD affects 20-30% of the general population, with prevalence increasing to 70% in obesity and 90% in diabetes, as stated by Praxis Medical Insights 10, 9
Hepatic steatosis is strongly associated with metabolic syndrome components, including abdominal obesity, insulin resistance/type 2 diabetes, hypertension, and dyslipidemia, according to Praxis Medical Insights 7

The American Association for the Study of Liver Diseases recommends that the diagnosis of hepatic steatosis require demonstrating hepatic steatosis either by imaging showing ≥5% fat accumulation or by histology, combined with exclusion of secondary causes, as reported by Praxis Medical Insights 7
Ultrasound is commonly used as first-line investigation, showing increased liver echogenicity compared to renal cortex, with sensitivity of 84.8% and specificity of 93.6% for moderate to severe hepatic fat deposition, according to Praxis Medical Insights 10
Liver biopsy remains the most sensitive means of obtaining comprehensive information and is capable of identifying steatohepatitis and staging liver fibrosis, which have important prognostic implications, as stated by Clinical Gastroenterology and Hepatology 5, 6