SUPERStudy:Non-Alcoholic Fatty Liver Disease (NAFLD)

By usmlevideoss

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders characterized by excessive fat accumulation (>5% of hepatocytes) in the liver in the absence of significant alcohol consumption or secondary causes of fat accumulation. It encompasses simple steatosis and non-alcoholic steatohepatitis (NASH), which can progress to fibrosis, cirrhosis, and hepatocellular carcinoma.

Etiology

  • Insulin resistance (central to pathogenesis)
  • Obesity (particularly visceral adiposity)
  • Dyslipidemia (elevated triglycerides, low HDL)
  • Type 2 diabetes mellitus
  • Metabolic syndrome
  • Genetic predispositions (e.g., PNPLA3 and TM6SF2 polymorphisms)
  • Environmental factors (high-fat diet, sedentary lifestyle)

Epidemiology

  • Prevalence: Affects ~25% of the global population. Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States, as well as worldwide.
  • Age: Common in middle-aged adults; increasing in children due to rising obesity.
  • Gender: Slight male predominance; postmenopausal women at increased risk.
  • Strong association with obesity, metabolic syndrome, and type 2 diabetes.

Pathophysiology

  • Insulin resistance: Increases lipolysis, leading to free fatty acid influx into the liver.
  • Lipid accumulation: Imbalance between lipid uptake, synthesis, oxidation, and export.
  • Oxidative stress: Excess fat leads to lipid peroxidation and production of reactive oxygen species.
  • Inflammation: Kupffer cells and cytokines (e.g., TNF-α, IL-6) perpetuate liver injury.
  • Fibrosis progression: Activation of hepatic stellate cells leads to collagen deposition.

Clinical Manifestations

  • Often asymptomatic, detected incidentally via elevated liver enzymes or imaging.
  • Symptoms (if present): Fatigue, vague right upper quadrant discomfort.
  • Advanced disease: Signs of cirrhosis (jaundice, ascites, encephalopathy).

Diagnosis

NAFLD is a clinical diagnosis after exclusion of other causes of liver disease.

1.Laboratory findings:

  • Elevated ALT > AST (but <2:1 ratio).
  • Normal bilirubin unless advanced disease.

2.Imaging:

  • Ultrasound: Increased echogenicity (“bright liver”).
  • MRI/CT: Quantification of fat.
  • FibroScan (elastography): Assesses fibrosis.

3.Histology (gold standard):

  • Simple steatosis or NASH with ballooning hepatocytes, inflammation, and/or fibrosis.

Treatment

1.Lifestyle modifications (cornerstone):

  • Weight loss (7-10% reduction improves histology).
  • Diet: Mediterranean diet, reduced fructose and saturated fats.
  • Regular physical activity.

2.Pharmacologic therapy (in select cases):

  • Pioglitazone (improves steatosis and inflammation in NASH).
  • GLP-1 receptor agonists (e.g., liraglutide).
  • Vitamin E (antioxidant effect).

3.Management of comorbidities:

  • Control diabetes, hypertension, and dyslipidemia.

4.Advanced disease:

  • Consider liver transplant for cirrhosis or hepatocellular carcinoma. NAFLD is currently the leading indication for liver transplantation in the United States.

Prognosis

  • Simple steatosis: Generally benign, low risk of progression.
  • NASH: ~20-30% progress to cirrhosis; 2-3% may develop hepatocellular carcinoma.
  • Prognosis is worse with comorbidities like diabetes, obesity, and advance D cells and fibrosis.

SUPERPoint

NAFLD is the most common chronic liver disease globally and is closely linked to obesity, insulin resistance, and metabolic syndrome, making lifestyle interventions critical for prevention and treatment.

SUPERFormula

PNPLA3 genetic predisposition + Insulin resistance + Obesity + Metabolic syndrome + Elevated ALT > AST + Ultrasound is significant for increased echogenicity (“bright liver”) + eleastography reveals increased liver fibrosis = Non-alcoholic fatty liver disease (NAFLD).

Reference: 

Liu AF, Viveiros K. Nonalcoholic Fatty Liver Disease. In: Friedman S, Blumberg RS, Saltzman JR. eds. Greenberger’s CURRENT Diagnosis & Treatment Gastroenterology, Hepatology, & Endoscopy, 4e. McGraw Hill Education; 2022.