Primary biliary cirrhosis

Definition

• Autoimmune disorder with a genetic predisposition
  • That causes slow progressive damage to interlobular bile ducts
  • Resulting biliary obstruction → Cirrhosis
• 9:1 F:M
• Associations (other autoimmune conditions)
  • RA
  • Scleroderma
  • Sicca complex
  • Autoimmune thyroiditis

Clinical

• Insidious presentation
• Pruritus, fatigue
• Hepatomegaly
• Jaundice
• Splenomegaly
• Xanthelasma
• Hyperpigmentation

Investigations

• Deranged cholestatic LFTs
• Anti-mitochondrial antibodies against PDC-E2 in 90%
• Antinuclear antibodies – prognostic
  • If you have specifically anti-glycoprotein-210 or anti-p62 antibodies
    • Correlates with progression to end-stage liver failure
• Anti-centromere antibodies correlated with portal hypertension
• Liver biopsy to determine stage of disease
  • Inflammation of bile ducts with intraepithelial lymphocytes
  • Periductal epithelioid granuloma

Pathology

• Stages of Disease
  • Stage 1 – DESTRUCTION - Portal Stage:
    • Normal sized triads, portal inflammation, subtle bile duct damage. Granulomas are often detected in this stage
  • Stage 2 – PROLIFERATION - Periportal Stage:
    • Enlarged triads; periportal fibrosis and/or inflammation
    • Typically characterized by the finding of a proliferation of small bile ducts
  • Stage 3 – FIBROSIS - Septal Stage:
    • Active and/or passive fibrous septa
  • Stage 4 – CIRRHOSIS
    • Biliary Cirrhosis: Nodules present; “Garland” or jigsaw puzzle pattern

Relationship with Gluten

• 57% of patients with acute liver failure have anti-transglutaminase antibodies
• Suggests a role of gluten sensitivity
• PBC is considerably more common in gluten sensitive enteropathy than the normal population
• In some cases of disease protein expression may cause an immune tolerance failure

Management

• Ursodeoxycholic acid (Ursodiol)
  • Reduces cholesterol absorption hence in theory reduced bile acid production
  • Minimal effect on symptoms
  • Impact on prognosis controversial
• Cholestyramine (bile acid sequestrant)
  • May absorb bile acids in the gut and be eliminated, can help with itch
• Multivitamins and calcium
  • Poor lipid-dependent absorption of Vitamins A, D, E, K
• In advanced cases,
  • Liver transplant, if successful, results in a favourable prognosis

Prognosis

• Bilirubin level is an indicator of the prognosis of PBC
  • 2–6 mg/dL - mean survival time 4.1 years,
  • 6–10 mg/dL - mean survival time of 2.1 years
  • 10 mg/dL - mean survival time of 1.4 years.
• After liver transplant:
  • Recurrence rate may be as high as 18% at 5 years
  • Up to 30% at 10 years
  • There is no consensus on risk factors for recurrence of the disease.
• Patients with PBC have an increased risk of HCC