Primary Biliary Cirrhosis

Question 1

Define primary biliary cirrhosis

Answer 1

Chronic autoimmune disease of the small intrahepatic bile ducts that is characterised by cholestasis, progressive bile duct damage (and eventual loss) due to chronic portal tract inflammation.

Interlobular bile ducts damaged by chronic autoimmune granulatomous inflammation, causing cholestasis which may lead to fibrosis, cirrhosis and portal hypertension

Question 2

Aetiology of primary biliary cirrhosis

Answer 2

loss of immune tolerance to self-mitochondrial proteins
Autoimmune damage to small bile ducts → intrahepatic cholestasis
Progressive bile duct damage (and eventual loss) occurring in context of chronic portal tract inflammation
Fibrosis develops due to original insult and secondary effects of toxic bile acids retained in the Liver → Cirrhosis

Question 3

Risk factors for primary biliary cirrhosis

Answer 3

Female sex
Family history
Age between 45-60
FHx or Hx of autoimmune diseases e.g. RA, thyroid disease, T1DM, Sjogren’s
Hypercholesterolaemia
Many UTIs
Smoking
Pregnancy
Use of nail polish/hair dye

Question 4

Symptoms of primary biliary cirrhosis

Answer 4

Often asymptomatic and diagnosed after incidental finding raised ALP

Itch (due to bile salts)
Fatigue / sleep disturbance / daytime somnolence
Dry eyes and dry mouth
Sleep disturbance
Postural dizziness/blackouts
Weight loss and other metabolic features of malabsorption
Memory and concentration problems (due to autonomic dysfunction)

Question 5

Signs of primary biliary cirrhosis on examination

Answer 5

Dry eyes and mouth
Hepatomegaly
Jaundice
Ascites
Splenomegaly
Skin pigmentation
Xanthelasmata

Question 6

Investigations for primary biliary cirrhosis

Answer 6

LFTs: Raised ALP + GGT, raised ALT and bilirubin
AMA: positive
USS abdomen: exclude obstructive lesions (required)

Serum albumin: reduced
ANA: staining pattern of multiple dots within the nucleus or along the rim
ELISA testing: either indicates presence of AMA or ANA
Clotting studies: PT prolonged
Serum immunoglobulin: polyclonal elevation of IgM and IgG
Serum alpha-fetoprotein: exclude carcinoma
TFTs: TSH raised
Lipid profile: Cholesterol raised

Upper GI endoscopy: exclude varices
Liver biopsy: bile duct lesions, granulomata formation, less bile ducts

Question 7

Management for primary biliary cirrhosis

Answer 7

1. Slow/stop progression of disease to prevent cirrhosis

First line: Ursodeoxycholic acid
Second line: Obeticholic acid
End-stage disease: liver transplantation (PBC can recur in the transplanted organ in up to 1/3)

2. Symptomatic management
   Pruritus:
   First line: Colestyramine
   Second line: Rifampicin or naltrexone
   Third line: SSRIs

Question 8

Complications of primary biliary cirrhosis

Answer 8

Malabsorption of fat-soluble vitamins (ADEK) due to cholestasis and reduced bilirubin in the gut lumen:
- Osteoporosis / Osteomalacia
- Coagulopathy
Portal hypertension
Hepatocellular carcinoma

Question 9

Prognosis for primary biliary cirrhosis

Answer 9

a slowly progressive condition
Many patients die of other causes before ESLD
There is approximately a doubling of risk of liver-related death in PBC patients compared with in relevant comparator populations.