Primary sclerosing cholangitis Flashcards
What is the end point of primary sclerosing cholangitis (PSC)?
End-stage liver disease
What characterises PSC?
Progressive inflammation, fibrosis, and stricturing of the intrahepatic and extrahepatic bile ducts
How is the diagnosis of PSC best made?
Contrast cholangiography
What does PSC look like on contrast cholangiography?
Diffuse multifocal strictures of the bile ducts
Focal dilation of the bile ducts as well, leading to a ‘beaded’ appearance
T/F PSC is more common in males
True
T/F There is an increase in incidence of PSC in first degree relatives
True, but still low
Is there a link between ulcerative colitis and PSC?
Yes
UC has been reported in anywhere between 25 and 90% of PSC patients
Is there an association between PSC and any other GIT disorders?
Yes
Crohn’s disease (around 15%)
How does the epidemiology of PSC, specifically gender distribution, change when considering those that have UC?
Rather than being male dominant, PSC becomes equally distributed between the genders
What are some possibly aetiologies of PSC?
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
Describe the chronological relationship between PSC and UC onset
PSC may develop years after colectomy for UC
UC may first present after liver transplantation has been performed for PSC
What is the most likely aetiology for PSC?
That it is a multifocal disorder, or that PSC represents multiple diseases with a similar clinical presentation
Is there also a relationship between PSC and CF?
Yes
similar radiologic and histologic pictures
Evidence of increased levels of CFTR
What is the natural history of PSC?
Progressive disorder
Leads to complications of cholestasis and hepatic failure
What is the median survival without liver transplantation?
10-12 years
What is a poor prognostic factor at time of diagnosis?
If they are already symptomatic at diagnosis, this is a very poor prognostic marker
What percentage of patients with UC have PSC?
~5%
Hence you should not screen UC patients for PSC unless LFTs deranged
What are some findings on physical exam in PSC?
Jaundice
Hepatomegaly
Splenomegaly
Excoriations
Normally exam is normal though
What do LFTs normally show with PSC?
Cholestatic patern
Elevation of serum alkaline phosphatase predominating
What are the normal radiographic findings in PSC?
Bile ducts with wall thickening, dilations, and strictures
‘string of beads’ appearance
If a PSC patient is symptomatic at the time of diagnosis, what symptom will that most commonly be?
Fatigue or pruritus
How bad will pruritus be in PSC patients?
Can be extremely bad and debilitating
What is the normal treatment for intractable pruritus in PSC?
Indication for liver transplantation
What are bilirubin levels like in PSC patients that have pruritus?
Normal
What are some autoantibodies that you can test for in PSC?
anticardiolipin (most important)
antinuclear
Antismooth muscle
thyroperoxidase
rheumatoid factor
How important is autoantibody testing in PSC?
Not that important or useful
Mayo risk score for PSC does include anticardiolipin autoantibodies though
What is the typical description of the stricutres of PSC?
Short
multifocal
Annular
Alternate with normal or mildly dilated segments
What would long strictures in the bile ducts be concerning for?
Cholangiocarcinoma
Why should you test IgG4 levels in PSC?
IgG4-associated disease may have a more rapidly progressive course
Appears to be less responsive to corticosteroids
Why should you test for antimtochondrial antibodies in PSC?
To help exclude primary biliary cirrhosis
How is the diagnosis of PSC typically established?
By the demonstration of characteristic stricturing patterns on cholangiography
What are the three methods by which cholangiography can be obtained?
MRCP
ERCP
Percutaneous transhepatic cholangiography
Which of the three cholangiography methods for the diagnosis of PSC is the best?
MRCP
Less invasive, with comparable diagnostic ability to ERCP
T/F The strictures of PSC occur anywhere along the extrahepatic biliary tree only
F
They occur anywhere in the biliary tree, whether intra- or extra
Is it more common to have only extra-hepatic bile duct involvement in PSC?
No
It’s far more common (87%) to have involvement of the entire biliary tree
What are the most important DDxs for PSC?
Secondary causes of sclerosing cholangitis
IgG4-associated cholangitis/autoimmune pancreatitis
PSC-autoimmune hepatitis overlap syndrome
What are some secondary causes of sclerosing cholangitis?
Chronic bacterial cholangitis
Infection or ischaemic cholangitis
Cholangiocarcinoma
Choledocholithiasis
Eosinophilic cholangitis
Portal hypertensive biliopathy
Recurrent pancreatitis
Surgical biliary trauma
How often does IgG4 associated cholangitis occur without autoimmune pancreatitis?
Rarely
Usually happen at the same time
What agent can you add to your treatment of PSC, if they have IgG4-associated cholangitis?
Glucocorticoids
What are some important complications of PSC?
End-stage liver disease
Vit ADEK deficiency
Metabolic bone disease
Cholangiocarcinoma
Hepatocellular carcinoma in those with cirrhosis
Colorectal carcinoma in those patients with UC
Talk about bone disease in PSC
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
What are the goals in management of PSC?
Retardation and reversal of the disease process
Management of progressive disease and its complications
What immunosuppressive agents have proved successful in PSC?
None
Current trials looking at ursodeoxycholic acid
How does ursodeoxycholic acid work?
Protection of cholangiocytes against cytotoxic hydrophobic bile acids
Stimulation of hepatobiliary secretion
Protection of hepatocytes against bile acid-induced apoptosis
Induction of antioxidants
What does ursodeoxycholic acid do for PSC patients, and what does it not do?
Does improve liver biochemical markers
Does not result in a survival benefit or a delay in the need for liver transplant
What is the only current definitive treatment for PSC?
Liver transplantation
