Primary biliary cirrhosis

• Chronic progressive liver disease; > 90% women; 30-65 years
• Characterised by destruction of intrahepatic bile ducts, portal inflammation and scarring, leading relentlessly to cirrhosis and liver failure
• Presence of granulomata in portal tracts.
• Both B and T cells found; both CD4+ and CD8+
• Failure of biliary secretion leads to retention of toxic substances and hence secondary chemical damage to hepatocytes.
• Induction of class II expression on both biliary epithelium and hepatocytes: exacerbated immune mediated damage.
  
• May be asympomatic for some time

1. Signs of portal hypertension: hepatomegaly, splenomegaly, variceal bleeds, ascites
2. Signs of cholestasis: pigmentation, gallstones, steatorrhoea, pruritis, jaundice
3. Abdominal pain
4. Osteoporosis (important co-existing problem; steroids contra-indicated as can exacerbate this)
5. Associated with other auto-immune diseases: e.g. Sjogren's syndrome; thyroid auto-immunity; SLE; scleroderma; rheumatoid arthritis; CREST; dermatomyositis; renal tubular acidosis

• Increased prevalence of hepatocellular cancer and breast cancer
  
• Less rapid disease progression: asymptomatic patients and those with hepatic granulomas
  
• More rapid disease progression: symptomatic, older, hepatomegaly, high bilirubin, low albumin, cirrhosis
  
• Some chronic hepatitis patients are anti-mitochondrial antibody positive, and have a mixed clinical pattern.
  
• Some primary biliary cirrhosis may present at the cirrhotic stage, with raised anti-mitochondrial antibody levels
  
• Almost all patients who have anti-mitochondrial antibodies will go on to develop primary biliary cirrhosis
  

• Auto-antibodies
• Raised serum immunoglobulin: IgM
• Complement activation
• T cells: decrease in number as disease progresses
• Possible association with HLA-DR8
• (Raised bilirubin, alkaline phosphatase and lipids)
  

• Granulomas
• Increased expression of class I MHC on bile duct epithelial cells
• Aberrant expression of class II MHC on bile duct epithelial cells
• T cell infiltrate around the bile ducts – CTL may be early event, but more usual to see CD4+ T cells seen around the bile ducts.
• Excess IgM producing B cells around the bile ducts.
• Features have been said to resemble either (i) graft - versus - host disease; or (ii) transplant rejection.
• (Accumulation of excess copper)
  

1. symptomatic relief [including anti-cholestatic (urosodexycholic acid, which may provide symptomatic relief but does not affect prognosis) and anti-pruritic agents]
2. immunomodulatory and immunosuppressive agents [steroids, azathioprine, cyclosporin, FK506, penicillamine; colchicine, methotrexate] have all been attempted but have not been shown to be effective
3. transplantation for end-stage disease

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