• Progressive process of inflammation, cellular injury and necrosis, diffuse fibrosis, and formation of regenerative nodules
  • Loss of lobular and vascular architecture
  • Irreversible in advanced stages
  • Intrahepatic portal hypertension owing to increased resistance at the sinusoid, compression of the central veins, and anastomosis between the arterial and portal systems


  • Chronic viral hepatitis C (most common cause in the U.S.)
  • Chronic alcohol abuse (second most common cause in the U.S.)
  • Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
  • Other: Chronic hepatitis B and/or D
  • Metabolic:
    • Hereditary hemochromatosis
    • Wilson disease
    • Porphyria
  • Drugs:
    • Acetaminophen
    • Methotrexate
    • Amiodarone
    • Methyldopa
  • Hepatic congestion:
    • Right-sided heart failure
    • Pericarditis
    • Budd–Chiari syndrome (hepatic venous outflow obstruction)
  • Infiltrative/autoimmune:
    • Sarcoidosis
    • Amyloidosis
    • Primary biliary cholangitis (PBC) or secondary (sclerosing cholangitis)
    • Hepatocellular carcinoma, diffusely infiltrating
  • Infections:
    • Brucellosis
    • Echinococcosis
    • Tertiary syphilis
    • Schistosomiasis

Pediatric Considerations
  • Congenital: Arteriohepatic dysplasia, biliary atresia
  • Cystic fibrosis, α1-antitrypsin deficiency
  • Metabolic
  • Fructosemia, tyrosinemia, galactosemia, glycogen storage diseases
  • Infectious
  • Congenital hepatitis B

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