Hepatobiliary - Primary Sclerosing Cholangitis, Primary Biliary Cholangitis

Question 1

Primary sclerosing cholangitis (PSC) - what is it?

Answer 1

Primary sclerosing cholangitis is a condition where the intrahepatic or extrahepatic ducts become strictured and fibrotic

This causes an obstruction to the flow of bile out of the liver and into the intestines

Sclerosis refers to the stiffening and hardening of the bile ducts

Cholangitis is inflammation of the bile ducts

Chronic bile obstruction eventually leads to liver inflammation (hepatitis), fibrosis and cirrhosis.

Question 2

PSC - which disease has an established association with PSC?

Answer 2

Ulcerative Colitis

4% of patients with UC have PSC, 80% of patients with PSC have UC

Question 3

PSC - risk factors?

Answer 3

• Male
• Aged 30-40
• Ulcerative Colitis
  
  • Family History

Question 4

PSC - clinical features?

Answer 4

cholestasis, so jaundice, pruritus, raised bilirubin + ALP

RUQ pain

fatigue

Question 5

PSC - what are the two diagnostic investigations?

Answer 5

endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP)

Shows multiple biliary strictures giving a ‘beaded’ appearance

Question 6

PSC - what does MRCP involve?

Answer 6

This involves an MRI scan of the liver, bile ducts and pancreas

Question 7

PSC - which antibodies are present and positive for PSC?

Answer 7

Antineutrophil cytoplasmic antibody (p-ANCA) in up to 94%

(p-ANCA, P in PSC)

Antinuclear antibodies (ANA) in up to 77%

Anticardiolipin antibodies (aCL) in up to 63%

Question 8

PSC - what are complications that can arise?

Answer 8

cholangiocarcinoma (in 10%)

increased risk of colorectal cancer

Cirrhosis and liver failure

Question 9

PSC - what are the management options?

Answer 9

Liver transplant can be curative, associated with problems

ERCP can be used to dilate and stent any strictures

Colestyramine is a bile acid sequestrate in that it binds to bile acids to prevent absorption in the gut and can help with pruritus due to raised bile acids

Question 10

Primary Biliary Cirrhosis (PBC) - what is it?

Answer 10

Also known as Primary Biliary Cholangitis

Primary biliary cirrhosis is a condition where the immune system attacks the small bile ducts within the liver

Question 11

PBC - what does it affect first, and what happens?

Answer 11

The first parts to be affected are the intralobar ducts, also known as the Canals of Hering

This causes obstruction of the outflow of bile, which is called cholestasis

Back-pressure of the bile obstruction eventually progresses to fibrosis, cirrhosis and liver failure

OR

Progressive cholestasis which may lead to cirrhosis

Question 12

PBC - clinical features?

Answer 12

Build up of bile acids, bilirubin and cholesterol in blood, as obstruction not letting them being excreted therefore:

• Early: may be asymptomatic (e.g. raised ALP on routine LFTs)
• Fatigue
• Pruritus
• GI disturbance and abdominal pain
• Jaundice
• Pale stools
• Xanthoma and xanthelasma, cholesterol deposits
• Signs of cirrhosis and failure (e.g. ascites, splenomegaly, spider naevi)

Question 13

PBC - what diseases is PBC associated with?

Answer 13

• Sjogren’s syndrome (seen in up to 80% of patients)
• rheumatoid arthritis
• systemic sclerosis
  
  • thyroid disease

Question 14

PBC - how do you diagnose?

Answer 14

• immunology
  
  • anti-mitochondrial antibodies (AMA) M2 subtype, highly specific
  • smooth muscle antibodies
  • raised serum IgM
• imaging
  
  • RUQ ultrasound or MRCP
• LFTs: Alkaline phosphatase is first liver enzyme to be raised (as with most obstructive pathology)

Question 15

PBC - pharmacological management?

Answer 15

• first-line: ursodeoxycholic acid
  
  • reduces the intestinal absorption of cholesterol
• pruritus: cholestyramine, bile acid sequestrate in that it binds to bile acids to prevent absorption in the gut and can help with pruritus due to raised bile acids
• fat-soluble vitamin supplementation
• liver transplantation
  
  • e.g. if bilirubin > 100 (PBC is a major indication)
  • recurrence in graft can occur but is not usually a problem

Question 16

PBC - complications from disease progression?

Answer 16

Some people live decades without symptoms

Advanced liver cirrhosis and portal hypertension

• cirrhosis → portal hypertension → ascites, variceal haemorrhage
• osteomalacia and osteoporosis
• significantly increased risk of hepatocellular carcinoma