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Primary biliary cirrhosis

  • Chronic, progressive cholestatic liver disease. Earlier stage of primary sclerosing cholangitis
  • Strongly associated with anti-mitochondrial antibodies (diagnostic)
  • Granulomatous inflam of the portal tracts – causes progressive damage and loss of the small bile ducts
    • Leads to fibrosis and cirrhosis of liver

Epidemiology

  • F:M = 9:1
  • MC in cigarette smokers

Pathophysiology

  • Closely related with other autoimmune non-hepatic diseases – e.g. thyroid disease
  • Genetic association with HLA-DR8
  • AMA are directed at pyruvate dehydrogenase complex
    • A mitochondrial complex that plays a role in cellular energy generation
  • PBC-specific ANA is directed at the nuclear pore antigen gp210 – characteristic staining in IFA (nuclear dots)
    • Shouldn’t be mistaken for homogenously staining ANA in autoimmune hepatitis (AIH)
  • Elevation in serum Igs – typically IgM (unlike AIH)
  • Chronic granulomatous inflammation destroys the interlobular bile ducts
  • Progressive lymphocyte-mediated inflam damage causes fibrosis
    • Spreads from the portal tracts to liver parenchyma, eventually leads to cirrhosis

Clinical features

  • Systemic sx such as fatigue may precede a diagnosis for years. Pruritis (common)
  • Bone pain/fractures – due to osteomalacia (fat-soluble vitamin malabsorption) or osteoporosis (hepatic osteodystrophy)
  • Weight loss
  • Jaundice prominent in late disease
  • Xanthomatous deposits around eye
  • Mild hepatomegaly (common)
  • Splenomegaly – increases as portal HTN develops
  • Associated diseases – Sicca syndrome , systemic sclerosis, celiac disease, thyroid disease

Investigations

  • LFTs – ↑ALP
  • ↑cholesterol
  • AMA – 95% pts
  • ANA + ASMA – 15% pts
  • USS – alteration of liver architecture
  • MRCP/ERCP
  • Liver biopsy – portal tract infiltrates, fibrosis

Management

  • Ursodeoxycholic acid (UDCA) [13-15mg/kg/d]
    • Improves bile flow, replaces toxic bile acids, reduces apoptosis of biliary epithelium
  • Immunosuppressants – corticosteroids, azathioprine, penicillamine, ciclosporin
  • Pruritis – main sx requiring treatment
    • Colestyramine (anion-binding resin) – [4-16g/d PO] mixed in orange juice
    • Rifampicin – [150mg/d]
    • Naltrexone (opioid antagonist) – [25mg/d]
  • Transplant (bilirubin >5.8 mg/dl)
  • Malabsorption – replacement of fat soluble vitamins (ADEK)
  • Bone disease – calcium and vit D3. Bisphosphonaes if osteoporosis

DDx

Sarcoidosis, brucellosis, parasites, TB

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