Chronic Hepatitis



  • Chronic hepatitis is a continuous inflammation of the liver that can lead to cirrhosis.
  • Features of chronic inflammation include raised transaminases for >6 months and histologic evidence of hepatocellular injury, cholestasis, or presence of inflammatory infiltration.


Depends on the cause of the underlying disease

  • Nonalcoholic steatohepatitis (NASH) is a leading cause of elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST).
  • Hepatitis B: common in immigrant children from Asia and Eastern Europe
  • Hepatitis C: common in those who had blood products before screening became available, history of IV drug use, tattoos, or in immigrant children with shared vaccination needles
  • Hepatitis E: can cause chronic hepatitis in pregnant women
  • Wilson disease presents mainly in older children (>2 years of age) and adolescents.
  • Autoimmune hepatitis (AIH) is more common in females and patients >6 months of age. AIH may be associated with other autoimmune conditions such as primary sclerosing cholangitis (PSC), type I diabetes, inflammatory bowel disease, autoimmune thyroiditis, and celiac disease.
  • Cystic fibrosis (CF) may present with cholestasis of the newborn; 5–10% of patients with CF develop advanced liver disease in childhood.
  • α1-antitrypsin (AAT) deficiency phenotype (Pi) Pi*MM is wild type; Pi*ZZ or Pi*SZ cause liver disease.


Chronic hepatitis involves a continuous process of liver injury and regeneration.

  • Pattern of liver injury and histopathology varies depending on the clinical diagnosis.
  • The response to chronic liver injury is the same across most liver diseases: development of fibrosis.
  • The liver is in a constant equilibrium between the production and breakdown of extracellular matrix (ECM) proteins, which includes collagen and others.
  • Hepatitis causes increased cellular activation and transformation (e.g., activated stellate cells differentiate to myofibroblasts), which leads to the accumulation of ECM.
  • Over time, as the connective tissue bands thicken they can extend from portal triad to portal triad (bridging fibrosis) or to central veins with eventual formation of nodules (cirrhosis).


  • Autoimmune liver disease: AIH or PSC
  • Celiac disease associated with hepatitis
  • Viral hepatitis
  • Nonalcoholic fatty liver disease (NAFLD), or specifically NASH
  • Congenital hepatic fibrosis
  • Genetic disease
    • AAT deficiency
    • Alagille syndrome
    • CF
    • Progressive familial intrahepatic cholestasis (PFIC) syndromes
    • Wilson disease
  • Metabolic disease
    • Mitochondrial disease
    • Lysosomal acid lipase deficiency (LAL-D)
    • Lysosomal storage disorders
    • Peroxisomal disease
    • Lipid storage disease
    • Glycogen storage disease (GSD)
    • Wilson disease and others
  • Drug-induced liver injury (DILI)
    • Parenteral nutrition–associated liver disease
    • Chemotherapy: methotrexate, 6-mercaptopurine, thioguanine
    • Isoniazid
    • Valproate
  • Liver disease associated with other chronic diseases
    • Hypothyroidism, hyperthyroidism
    • Growth hormone deficiency/panhypopituitarism
    • Diabetes mellitus (uncontrolled hyperglycemia)
    • Congestive hepatopathy (cardiac: right-sided heart failure or hypertension, such as post-Fontan procedure; pulmonary hypertension)
    • Autosomal recessive polycystic kidney disease
    • Langerhans cell histiocytosis
    • Immunodeficiency

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