PSC and PBC

Question 1

Describe the natural history of primary sclerosing cholangitis.

Answer 1

bile duct injury characterized by inflammation, fibrosis, and strictures; often in young men, usually before 45yo, relatively rare
generally a slow progression to secondary biliary cirrhosis, portal HTN and liver failure
7-15% will develop cholangiocarcinoma

Question 2

Describe the pathogenesis of PSC

Answer 2

autoimmune destruction of ducts, elevated immunoglobulins and autoantibodies form circulating immune complexes that cross react with biliary and colonic epithelium; some evidence for genetic predisposition and increased bacterial infiltration from portal circulation (initiation of T-cell reactivity)

ischemic disease can contribute
(80-90% have pANCA)

Question 3

What conditions are associated with PSC?

Answer 3

75% have ulcerative colitis, 5% have Crohn’s

Question 4

What is the clinical presentation of PSC

Answer 4

> 10% are asymptomatic
fatigue, weight loss, abdominal pain
pruritis (25-60%), episodic jaundice (30-70%)
rare acute cholangitis

Question 5

What clinical findings confirm PSC?

Answer 5

ERCP showing multifocal strictures with intervening normal/dilated ducts

ALKP 2x normal, elevated transaminases, bilirubin, PT, low albumin as disease progresses

pathological lesion is onion ring lesion around the bile duct due to inflammation (concentric fibrosis with surrounding inflammatory infiltrate)

Question 6

How do you treat PSC?

Answer 6

supportive care only- no intervention has slowed progression

endoscopy can be used to remove stones and dilated strictures (delays time to transplant)

definitive treatment is transplant

Question 7

Cholangiocarcinoma is signifantly linked to _____ and viral infection of the hepatocytes, and presentation in the ____ ducts has a worse prognosis than _____ ducts.

Answer 7

significantly linked to heavy alcohol and viral infection

worse in intrahepatic ducts than extra hepatic

(70% when multimodality therapy of surgery chemo and radiation used)

Question 8

Name risk factors for cholangiocarcinoma.

Answer 8

ongoing inflammation
PSC
gallstones
liver flukes
cysts (congenital)
toxic exposure

presents in 6th or 7th decade, men

Question 9

What is the presentation of cholangiocarcinoma? How do you confirm diagnosis?

Answer 9

non specific weight loss, anorexia, abdominal pain, failure to thrive, new onset or worsening LFTs jaundice

serum tumor markers CEA CA19-9, CT scan, MRC, definitive test is ERCP, difficult to diagnose with longstainc PSC

Question 10

Only _____ of proximal tumors and 60-70% of distal tumors are resectable.

Answer 10

20-30%, invasion of both lobes, major vessels make tumor unresectable, palliative endoscopic or percutaneous stenting possible

Question 11

Define primary biliary cirrhosis.

Answer 11

progressive chronic cholestatic autoimmune disease that affects the small intrahepatic bile ducts

90% women, caucasian, 6th and 7th decade

Question 12

What is the pathophysiology of PBC?

Answer 12

injury due to CTL mediated autoimmune destruction of epithelial cells of small bile ducts in lobule, arising in a susceptible individual as a result of exposure to some environmental stimulus

associated antimitochondrial antibodies (AMA), IgM hypergammaglobulinemia

chronic damage leads to obstruction of bile flowing cholestasis

Question 13

What are the clinical signs of PBC?

Answer 13

50% asymptomatic at time of diagnosis

fatigue and pruritus is very significant,
jaundice is a sign of disease progression

elevated AlkP, elevate bilirubin (progressive disease), positive AMA and hypergammaglobinemia

liver biopsy confirms with patchy destruction of interlobular bile ducts with mononuclear infiltrate and possible granulomas

Question 14

What are the metabolic sequelae of PBC?

Answer 14

weight loss, steatorrhea and vitamin deficiencies due to low bile secretion

bone disease because of vit D. malabsorption

Question 15

What is the course of PBC? What is the greatest predictor of survival?

Answer 15

variable with wide spectrum , generally slow progressive disease (some asympt with normal lifespan)

bilirubin is the greatest predictor of survival?

Question 16

What treatments are available for PBC management.

Answer 16

ursodeoxycholic acid (UDCA) has cytoprotective and cholerectic affect, it inihibits the absorption of toxic bile salts, replaces endogenous bile salts, stabilizes hepatocyte membranes against toxic bile salts

improves liver biochemisties and improves outcomes

pruritus: antihistamines, cholestyramine, rifampin, phenobarbital

replace vitamin deficiencies

liver transplant is only definitive tx.