Description

• 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.

Epidemiology

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.

Pathophysiology

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).

Etiology

• 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