What are the causes of hepatic steatosis (fatty liver disease)?

From the Guidelines

Fatty liver disease is primarily caused by excessive fat accumulation in liver cells, with the most common causes including obesity, insulin resistance, type 2 diabetes, high blood triglycerides, and metabolic syndrome, as well as certain medications and lifestyle factors, as supported by recent studies 1. The causes of fatty liver disease can be divided into two main types: alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD).

• The most common causes of NAFLD include:
  • Obesity
  • Insulin resistance
  • Type 2 diabetes
  • High blood triglycerides
  • Metabolic syndrome
• Certain medications can also contribute to the development of fatty liver disease, including:
  • Corticosteroids
  • Methotrexate
  • Tamoxifen
  • Some antiviral medications
• Lifestyle factors such as poor diet and sedentary behavior can also significantly increase the risk of developing fatty liver disease, as noted in a recent study 1. The underlying mechanism of fatty liver disease involves disruption of normal fat metabolism in the liver, where excess fat accumulates when the liver imports more fat than it can process or export, leading to inflammation and potential liver damage over time, as discussed in a recent review 1. Treatment of fatty liver disease typically focuses on addressing the underlying cause through lifestyle modifications, including weight loss, exercise, limiting alcohol consumption, and managing related conditions like diabetes and high cholesterol, as recommended in recent clinical practice guidelines 1.

From the Research

Causes of Fatty Liver

• Fatty liver disease can be caused by various factors, including alcohol consumption and metabolic syndrome 2, 3.
• Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders, such as central obesity, dyslipidaemia, hypertension, and hyperglycaemia 4, 5.
• The interaction between alcohol consumption and metabolic syndrome can exert synergistic or supra-additive effects on the development and progression of liver disease 2, 3.
• Obesity is a major risk factor for NAFLD, and the incidence of NAFLD is increasing with the rising prevalence of obesity 4, 3.
• Other factors that can contribute to the development of fatty liver disease include:
  • Hepatocyte injury
  • Inflammatory processes
  • Fibrosis 4
  • Insulin resistance
  • Inflammation
  • Apoptosis
  • Fibrogenic remodelling within the liver 5

Role of Alcohol Consumption

• Alcohol consumption can exacerbate the development and progression of fatty liver disease, particularly in individuals with metabolic syndrome 2, 3.
• Moderate alcohol consumption may have improved metabolic function in some individuals, but the results are controversial and depend on various factors 6.
• The combined effects of alcohol and obesity on liver disease can be additive or synergistic, leading to increased liver injury and disease progression 3.

Metabolic-Associated Fatty Liver Disease

• Metabolic-associated fatty liver disease is a new definition that is independent of alcohol consumption and is based on the detection of liver steatosis and metabolic dysfunction 6.
• This condition is closely linked to metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes 5.
• Therapeutic approaches for metabolic-associated fatty liver disease may involve treatments originally developed for type 2 diabetes or obesity, such as glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors 5.