Primary Biliary Cirrhosis

Question 1

What are the examination findings of primary biliary cirrhosis?
What are PBC specific features to look out for?

Answer 1

Middle aged female
Pruritus, jaundice 
Hypercholesterolaemia
Hepatomegaly +/- splenomegaly
Cirrhosis features and complications
Metabolic bone disease
Proximal myopathy
Other autoimmune conditions 

Occurs in middle aged female (75-90%)

1. Fatigue
2. Hyperbilirubinaemia - jaundice, pruritus
3. Generalised hyperpigmentation, worse over araes of exfoliation and lichenification - melanin deposit
4. Clubbing
5. Hypercholesterolaemia - xanthalesma, tendon xanthomata
6. Coagulopathy - petechiae, ecchymoses
7. Altered sex hormones - spider naevi
8. Hepatomegaly smooth and non-tender +/- hepatic venous hum
   8A. Splenomegaly and ascites in portal hypertension
9. Complications of cirrhosis - hepatic encephalopathy, portal hypertension

• To comment as isolated hepatomegaly or chronic liver disease if unable to elicit additional features

PBC specific features:
1. Metabolic bone disease - kyphosis, fractures, osteoporosis
2. Proximal myopathy/osteomalacia (proximal muscle wasting and weakness)
3. Autoimmune disease

Question 2

What are the definitive investigations for PBC?

Answer 2

1. Serum anti-mitochondrial antibodies - positive in 95%
   - 5% negative requiring PBC-specific autoantibodies (sp100, gp210)
   - HLA DR8
2. Blood tests
   A. LFT - cholestatic picture (high GGT, ALP, mild ALT, AST, hyperbilirubinaemia)
   - Some patients have AIH overlap ALT > 5x UL
   B. IgM - raised
   C. Lipid panel - hypercholesterolaemia
   D. FBC - mono-pancytopenia
3. Liver biopsy if required
   - Histology: portal tract granuloma, cirrhosis
4. US HBS, ERCP/MRCP to exclude extra-hepatic cholestasis (stones)

Question 3

Which drugs can cause cholestasis?

Answer 3

Phenothiazines
Sulphonamides
Penicillins
Rifampicin
Macrolides
Carbamazepine
Androgenic steroids
Diclofenac

Question 4

What is the management of primary biliary cirrhosis and its complications?

Answer 4

1. Involvement of multidisciplinary team
2. Supplement of fat soluble vitamins - A, D, E, K
3. Treatment of bone disease/osteoporosis (vitamin D, calcium, bisphosphonates)
4. Treatment of hypercholesterolaemia
5. Treatment of liver disease (ursodeoxycholic acid improves liver biochemistry and slows disease progression)
6. Management of pruritis (colestyramine, rifampicin, naltrexone)
   - Anti-histamines do not work and may worsen encephalopathy
7. Management of fatigue (manage co-existent anaemia and hypothyroidism)
8. Referral for transplantation (bilirubin >50, refractory fatigue or pruritis)
   - Recurrence in graft 15% at 3 years, 30% at 10 years

Question 5

What are the autoimmune conditions associated with PBC?
What are the features to look out for?

Answer 5

1. Graves: goitre, eye signs, thyroid acropachy, pretibial myxedema, hypo/hyperthyroidism
2. Sjogren: dry mouth, dry eyes
3. RA: symmetrical deforming arthropathy, eye signs
4. Scleroderma: telangiectasia, tight shiny skin, sclerodactyly, calcinosis, dystrophic nails
5. Dermatomyositis: heliotrope rash, Gottron papules
6. Idiopathic ILD: bibasal crepitations
7. MG: myasthenic facies, psotsis, proximal weakness, fatigability
8. Vitiligo: hypopigmented patches
9. Atrophic gastritis: pallor, koilonychia, IDA

Question 6

What are the typical presentation/features of PBC?
(demography, symptoms and signs)

Answer 6

1. Middle aged women (women > men 9:1)
2. Fatigue
3. Debilitating pruritus and jaundice
4. Hypercholesterolaemia
5. Liver disease occurs late

Question 7

Describe the pathogenesis of PBC

Answer 7

1. Anti-mitochondrial antibodies (AMA) as molecular mimicry
   - Likely from recurrent exposure to E. coli infections
   - AM antigens expressed on biliary epithelial cells
   - T cell mediated autoimmune attack against biliary cells
2. Chronic non-suppurative destructive cholangitis
   - Necrotising inflammatory process of portal tracts
   - Medium and small bile ducts infiltrated with lymphocytes, duct destruction
   - Mild fibrosis and bile stasis
3. Reduction of bile ducts, proliferation of smaller bile tubules
   - Increased fibrosis, expansion of periportal fibrosis to bridging fibrosis
4. Development of cirrhosis

Question 8

What are the complications of PBC?

Answer 8

1. Malabsorption - osteomalacia, coagulopathy
2. Thromboembolism - anti-thrombin antibodies
3. Sicca syndrome (70%)
4. Cirrhosis, portal hypertension and complications
5. Hepatocellular carcinoma (20x risk)