Primary Biliary Cholangitis

Question 1

Definition

Answer 1

Autoimmune condition characterised by granulomatous destruction of the small intrahepatic bile ducts and subsequent leakage into the circulation. The inflammatory process coupled with trapping of bile acids in the liver leads to progressive fibrosis, cirrhosis, and eventually liver failure

Question 2

Epidemiology

Answer 2

Middle aged: peak incidence between 45-60 years old
Female gender

Question 3

Risk factors

Answer 3

Autoimmune associations: see ‘pathophysiology’
Family history
Smoking
Chronic urinary tract infection
* more common than PSC *

Question 4

Aetiology

Answer 4

Autoimmune disease
- high incidence of autoantibodies, most characteristically directed against mitochondrial antigens (anti-AMA) attach bike ducts

Question 5

Pathophysiology

Answer 5

Progressive destruction on the biliary epithelial cell lining the small (interlobular) intrahepatic bile ducts/Cahal of Herring. The back pressure of the bile obstruction and the overall disease process causes the cells to die -> bile can enter bloodstream
Damage leads to inflammation which can lead to cirrhosis, fibrosis + liver failure
In the end stages of the disease there can be complete loss of small intrahepatic ducts.

Question 6

Signs

Answer 6

Skin hyperpigmentation (Jaundice)
Clubbing
Mild hepatosplenomegaly
Xanthelasma + xanthomata (late sign)
Scleral icterus (late sign)

Question 7

Symptoms

Answer 7

Initially asymptomatic, found on routine test
Pruritus
Weight loss
Fatigue
Dry eyes and mouth (Sjogren’s syndrome)
Obstructive jaundice:
- Icteric
- pale stool and dark urine

Question 8

Investigations

Answer 8

Anti-AMA Ab - present in 95% of patients (highly specific)
Antinuclear antibodies (ANA) - present in 50% of patients
Smooth muscle antibodies - 30% of patients, most associated with autoimmune hepatitis
LFTs
- High ALT
- High GGT
- High ALP
- High bilirubin
- Low albumin
FIRST LINE IMAGING = USS = to exclude extrahepatic cholestasis (blockage of the bile ducts outside the liver)
GOLD STANDARD: Liver biopsy
- portal tract infiltrate (lymphocyte + plasma cell)
- 40% granulomas
- portal tract fibrosis
… but INCREASED SERUM ALKALINE PHOSPHATASE + PBC SPECIFIC AUTOANTIBODIES (SUFFICIENT FOR DIAGNOSIS)

Question 9

Treatment

Answer 9

FIRST LINE: Ursodeoxycholic acid = A bile acid analogue which dampens the inflammatory response, acts as an anti-apoptotic agent, and improves cholestasis
Fat-soluble vitamin supplementation
Cholestyramine = Symptomatic relief of pruritus
SECOND LINE: Liver transplantation = end-stage disease with liver cirrhosis (MELD score > 15), if bilirubin values rising progressively > 50-85 umol/L

Question 10

Complications

Answer 10

Cirrhosis
Malabsorption of fats + A,D,E,K -> coagulopathy + steatorrhea
Osteomalacia
HCC
Hypercholaestrolaemia