Primary Biliary Cirrhosis - PBC

Primary Biliary Cirrhosis - PBC

 

Primary biliary cirrhosis (PBC) is an autoimmune liver disorder characterized by chronic, progressive cholestatic disease.

Epidemiology

  • Incidence – 25-27/1,000,000 in U.S.
  • Age – peak onset 40-50 years
  • Gender – F>M

Risk Factors

  • Presence of other autoimmune disorder
  • Family history of PBC
    • The relative risk of a family member of a first-degree relative of a PBC patient is 50- to 100-fold higher than the general population (ref. 6)

Pathophysiology

  • Etiology is unknown
  • Pathogenesis of PBC is believed to be caused by:
    • Defect in immune tolerance resulting in the expansion of self-mitochondrial antigen specific for T and B lymphocytes
    • Inappropriate immune response following environmental or infectious agent: modification of mitochondrial proteins or molecular mimicry
  • PBC is characterized by T-cell mediated destruction of bile duct epithelial cells resulting in loss of ducts and persistent cholestasis which may result to end-stage liver failure without treatment.

Clinical Presentation

  • Fatigue, pruritus, unexplained hyperlipidemia
  • Elevated hepatic enzymes
  • Associated frequently with other autoimmune disorders such as:
    • CREST
    • Sicca syndrome
    • Autoimmune thyroiditis
    • IgA deficiency
    • Chronic autoimmune hepatitis (AIH)
      • PBC and AIH have many overlapping immunologic features
        • Some patients may have serologic tests and histologic findings suggestive of AIH in addition to PBC
        • They may represent a continuum of a single disease entity

Diagnosis

  • Laboratory testing
    • PBC is strongly associated with antimitochondrial antibody (AMA), M2 type
      • However, M2 levels in PBC do not appear correlated with clinical activity or disease progression
      • Approximately 5-10% of PBC patients are AMA negative
    • PBC is also associated with anti-sp100 (20-30%) of patients and anti-gp210 (15-27% of patients)
      • Both antibodies are highly specific for PBC

Monitoring

  • Anti-gp210 is prognostic in PBC
    • Failure to see a decline with treatment increases risk of progression to end stage hepatic failure

Treatment

  • Medical therapy – ursodeoxycholic acid does not reduce the risk for mortality or liver transplantation
  • Liver transplantation for endstage cirrhosis

See Also