Incidence	- prevalence is 7.5 per 100,000 - marked increase in incidence in1st-degree relatives
Age	- 90% of patients are females aged 40-50 years
Sex	- F > M
Geography
Aetiology	- progressive destruction of the bile ducts leads to cirrhosis - ? immuological mechanism - serum antimitochondrial antibodies are found in almost all patients; M2 antigen is specific - however, presence in high titre is not related to the clinical picture - hence role in pathogenesis is unclear - environmental factor acting on genetically predisposed host ? E. coli - cell-mediated immunity is impaired - defective T-lymphocytes may be responsible for the damage
Presentation	- asymptomatic patients found to have hepatomegaly, raised serum ALP or autoantibodies - pruruitus - may be present years before jaundice - jaundice and hepatosplenomegaly - pigmented xanthelasma / cholesterol deposits on the creases of the hands may be seen Associations - autoimmune disorders e.g. Sjögren's, scleroderma, rheumatoid arthritis - Keratoconjunctivitis sicca in 70% of cases - renal tubular acidosis - membranous glomerulonephritis Differential diagnosis - autoimmune cholangitis - histological changes of PBC, but with negative AMA and positive anti-smooth muscle and ANAs - responds to steroids + azathioprine
Investigations	Mitochondrial antibodies - present in over 95% of cases; M2 is specific - other nonspecific antibodies may be present LFTs - ALP is often high Serum cholesterol - raised Serum IgM USS - diffuse alteration in liver structure - exclude extrahepatic biliary destruction in the jaundiced patient - ERCP/MRCP can be used to make sure the bile ducts are normal Liver biopsy - histology
Macro
Micro	- portal tract infiltrate of lymphocytes and plasma cells - granulomas in 40% (not specific) - later changes include loss of small bile ducts with ductular proliferation, portal tract fibrosis and cirrhosis
Staging
Serum markers
Management	Medical - ursodeoxycholate 10-15 mgkg/L is of beenfit in some patients and improves survival - supplementation of fat-soluble vitamins (A, D, K) - calcium supplements - hyperlipidameia should be treated - cholestyramine 4g tds - treats pruritus - rifampicin and naloxone hydrochloride are of benefit in controlling pruritus Surgical - orthoptic liver transplant
Prognosis	- variable - asymptomatic patients and those presenting with pruritus survive for > 20 years - symptomatic patients and those presenting with jaundice progress rapidly and die within 5 years from liver failure or bleeding varices - transplantation has a 5 year survival of 50%
Complications	- portal hypertension and GI haemorrhage - ascites - portosystemic encephalopathy - renal failure (hepatorenal syndrome) - osteoporosis - osteomalacia - polyneuropathy

Hepatobiliary medicine

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