Primary sclerosing cholangitis

Question 1

What is the end point of primary sclerosing cholangitis (PSC)?

Answer 1

End-stage liver disease

Question 2

What characterises PSC?

Answer 2

Progressive inflammation, fibrosis, and stricturing of the intrahepatic and extrahepatic bile ducts

Question 3

How is the diagnosis of PSC best made?

Answer 3

Contrast cholangiography

Question 4

What does PSC look like on contrast cholangiography?

Answer 4

Diffuse multifocal strictures of the bile ducts

Focal dilation of the bile ducts as well, leading to a ‘beaded’ appearance

Question 5

T/F PSC is more common in males

Answer 5

True

Question 6

T/F There is an increase in incidence of PSC in first degree relatives

Answer 6

True, but still low

Question 7

Is there a link between ulcerative colitis and PSC?

Answer 7

Yes

UC has been reported in anywhere between 25 and 90% of PSC patients

Question 8

Is there an association between PSC and any other GIT disorders?

Answer 8

Yes

Crohn’s disease (around 15%)

Question 9

How does the epidemiology of PSC, specifically gender distribution, change when considering those that have UC?

Answer 9

Rather than being male dominant, PSC becomes equally distributed between the genders

Question 10

What are some possibly aetiologies of PSC?

Answer 10

The link between PSC and UC suggests an autoimmune process

Could be an inflammatory reaction in the liver and bile ducts from chronic or recurrent entry of bacteria in the portal circulation

Ischaemic damage to the bile ducts may occur

Question 11

Describe the chronological relationship between PSC and UC onset

Answer 11

PSC may develop years after colectomy for UC

UC may first present after liver transplantation has been performed for PSC

Question 12

What is the most likely aetiology for PSC?

Answer 12

That it is a multifocal disorder, or that PSC represents multiple diseases with a similar clinical presentation

Question 13

Is there also a relationship between PSC and CF?

Answer 13

Yes

similar radiologic and histologic pictures

Evidence of increased levels of CFTR

Question 14

What is the natural history of PSC?

Answer 14

Progressive disorder

Leads to complications of cholestasis and hepatic failure

Question 15

What is the median survival without liver transplantation?

Answer 15

10-12 years

Question 16

What is a poor prognostic factor at time of diagnosis?

Answer 16

If they are already symptomatic at diagnosis, this is a very poor prognostic marker

Question 17

What percentage of patients with UC have PSC?

Answer 17

~5%

Hence you should not screen UC patients for PSC unless LFTs deranged

Question 18

What are some findings on physical exam in PSC?

Answer 18

Jaundice

Hepatomegaly

Splenomegaly

Excoriations

Normally exam is normal though

Question 19

What do LFTs normally show with PSC?

Answer 19

Cholestatic patern

Elevation of serum alkaline phosphatase predominating

Question 20

What are the normal radiographic findings in PSC?

Answer 20

Bile ducts with wall thickening, dilations, and strictures

‘string of beads’ appearance

Question 21

If a PSC patient is symptomatic at the time of diagnosis, what symptom will that most commonly be?

Answer 21

Fatigue or pruritus

Question 22

How bad will pruritus be in PSC patients?

Answer 22

Can be extremely bad and debilitating

Question 23

What is the normal treatment for intractable pruritus in PSC?

Answer 23

Indication for liver transplantation

Question 24

What are bilirubin levels like in PSC patients that have pruritus?

Answer 24

Normal

Question 25

What are some autoantibodies that you can test for in PSC?

Answer 25

anticardiolipin (most important) antinuclear Antismooth muscle thyroperoxidase rheumatoid factor

Question 26

How important is autoantibody testing in PSC?

Answer 26

Not that important or useful Mayo risk score for PSC does include anticardiolipin autoantibodies though

Question 27

What is the typical description of the stricutres of PSC?

Answer 27

Short multifocal Annular Alternate with normal or mildly dilated segments

Question 28

What would long strictures in the bile ducts be concerning for?

Answer 28

Cholangiocarcinoma

Question 29

Why should you test IgG4 levels in PSC?

Answer 29

IgG4-associated disease may have a more rapidly progressive course Appears to be less responsive to corticosteroids

Question 30

Why should you test for antimtochondrial antibodies in PSC?

Answer 30

To help exclude primary biliary cirrhosis

Question 31

How is the diagnosis of PSC typically established?

Answer 31

By the demonstration of characteristic stricturing patterns on cholangiography

Question 32

What are the three methods by which cholangiography can be obtained?

Answer 32

MRCP ERCP Percutaneous transhepatic cholangiography

Question 33

Which of the three cholangiography methods for the diagnosis of PSC is the best?

Answer 33

MRCP Less invasive, with comparable diagnostic ability to ERCP

Question 34

T/F The strictures of PSC occur anywhere along the extrahepatic biliary tree only

Answer 34

F They occur anywhere in the biliary tree, whether intra- or extra

Question 35

Is it more common to have only extra-hepatic bile duct involvement in PSC?

Answer 35

No It's far more common (87%) to have involvement of the entire biliary tree

Question 36

What are the most important DDxs for PSC?

Answer 36

Secondary causes of sclerosing cholangitis IgG4-associated cholangitis/autoimmune pancreatitis PSC-autoimmune hepatitis overlap syndrome

Question 37

What are some secondary causes of sclerosing cholangitis?

Answer 37

Chronic bacterial cholangitis Infection or ischaemic cholangitis Cholangiocarcinoma Choledocholithiasis Eosinophilic cholangitis Portal hypertensive biliopathy Recurrent pancreatitis Surgical biliary trauma

Question 38

How often does IgG4 associated cholangitis occur without autoimmune pancreatitis?

Answer 38

Rarely Usually happen at the same time

Question 39

What agent can you add to your treatment of PSC, if they have IgG4-associated cholangitis?

Answer 39

Glucocorticoids

Question 40

What are some important complications of PSC?

Answer 40

End-stage liver disease Vit ADEK deficiency Metabolic bone disease Cholangiocarcinoma Hepatocellular carcinoma in those with cirrhosis Colorectal carcinoma in those patients with UC

Question 41

Talk about bone disease in PSC

Answer 41

Due to osteoporosis, not osteomalacia, so vit D levels, though normally low, are not causative and replenishment does not prevent progression Concomitant bowel disease, common in PSC, does contribute normally Glucocorticoids also increases the rate of bone loss Has been proposed that a toxin or toxins retained because of cholestasis prevents osteoblast function

Question 42

What are the goals in management of PSC?

Answer 42

Retardation and reversal of the disease process Management of progressive disease and its complications

Question 43

What immunosuppressive agents have proved successful in PSC?

Answer 43

None Current trials looking at ursodeoxycholic acid

Question 44

How does ursodeoxycholic acid work?

Answer 44

Protection of cholangiocytes against cytotoxic hydrophobic bile acids Stimulation of hepatobiliary secretion Protection of hepatocytes against bile acid-induced apoptosis Induction of antioxidants

Question 45

What does ursodeoxycholic acid do for PSC patients, and what does it not do?

Answer 45

Does improve liver biochemical markers Does not result in a survival benefit or a delay in the need for liver transplant

Question 46

What is the only current definitive treatment for PSC?

Answer 46

Liver transplantation