Primary sclerosing cholangitis, primary biliary cirrhosis

Question 1

Define primary sclerosing cholangitis

Answer 1

Bile duct injury ( intra and extrahepatic) characterized by inflammation, fibrosis, and strictures

Question 2

In what population is primary sclerosing cholangitis most frequently seen?

Answer 2

Men, usually before 45

Question 3

Primary sclerosing cholangitis is an ______ disease

Answer 3

autoimmune
thought that an inflammatory/ infectious trigger initiates (bacteria from portal circulation??)
p-ANCA

Question 4

______ attack on the bile duct leads to scarring and strictures in PSC

Answer 4

T cell

Question 5

75% of people with PSC have ________

Answer 5

ulcerative colitis

Question 6

Describe the clinical presentation of PSC

Answer 6

asymptomatic in 10% of people

fatigue, abdominal pain, weight loss, pruritis, episodic jaundice, rarely acute cholangitis

Question 7

How is PSC diagnosed?

Answer 7

Alkaline phosphatase 2x normal
Elevated transaminases, bilirubin, prothrombin time
low albumin
ERCP is gold standard for diagnosis: multifocal strictures with intervening dilated ducts (beaded appearance)
onion ring appearance on liver biopsy

Question 8

Describe the prognosis of PSC

Answer 8

Slow progression to secondary biliary cirrhosis, portal HTN, liver failure
12 yr median survival
increased risk of cholangiocarcinoma

Question 9

Describe treatment of PSC

Answer 9

supportive- no intervention is successful in slowing disease progression (including immune suppression)
Endoscopic procedures to remove stones, stent strictures 
liver transplant (new liver will get PSC)

Question 10

_______ is the most common form of cholangiocarcinoma

Answer 10

Klatskin tumor (at bifurcation)

Question 11

List causes that have been associated with cholangiocarcinoma

Answer 11

PSC, gallstones, liver flukes, cysts, toxic exposure

Question 12

Describe the presentation of cholangiocarcinoma

Answer 12

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

Question 13

What are serum tumor markers for cholangiocarcinoma

Answer 13

CEA and CA 19-9

Question 14

Cholangiocarcinoma is extremely difficult to diagnose particularly with longstanding _______

Answer 14

PSC

Question 15

What is the prognosis for cholangiocarcinoma?

Answer 15

Extremely poor- 3 years if tumor is resectable, 1 year if not

Question 16

Define primary biliary cirrhosis

Answer 16

Progressive chronic cholestatic autoimmune disease that affects the small microscopic intrahepatic bile ducts

Question 17

What population is most commonly affected by primary biliary cirrhosis?

Answer 17

women»men

6th or 7th decade

Question 18

What immunologic abnormalities are seen in PBC?

Answer 18

T-cell mediated autoimmune response against bile duct epithelial cells

presence of antimitochondrial antibodies (AMA), IgM hypergammaglobulinemia, circulating immune complexes

Question 19

Describe the pathophysiology of PBC

Answer 19

Chronic damage/destruction of small ducts causes obstruction of bile flow and cholestasis»>hepatocyte injury, scarring + accumulation of bile acids

Possible cirrhosis and liver failure

Question 20

What are symptoms of PBC?

Answer 20

Very often asymptomatic at diagnosis

fatigue, pruritis worse at night, jaundice

Question 21

What is the underlying cause of the bone disease seen in PBC?

Answer 21

Bone disease – osteoporosis and osteomalacia secondary to Vit D malabsorption

Question 22

Describe the metabolic sequelae of PBC

Answer 22

Weight loss, steatorrhea, bone disease, vitamin deficiencies – bile secretory failure and low intestinal bile salt levels

Question 23

Describe the liver sequelae of PBC

Answer 23

Later stages- cirrhosis, portal hypertension
Ascites
Esophageal varices and bleeding
Increased risk of hepatocellular carcinoma

Question 24

How is PBC diagnosed?

Answer 24

Elevated ALKP, bilirubin
Positive AMA, hypergammaglobulinemia
Liver biopsy shows patchy destruction of interlobular bile ducts with mononuclear infiltrate and possible granulomas

Question 25

Describe the prognosis of PBC

Answer 25

Variable with wide spectrum
Generally slowly progressive disease and patients can be asymptomatic for years

Asymptomatic – normal life span
Symptomatic – median 11-12 year survival
Bilirubin greatest predictor of survival
Jaundice as marker of disease progression, cirrhosis

Question 26

______ is the greatest prognostic marker in PBC

Answer 26

Bilirubin

Question 27

In PBC, ______ is a marker of disease progression and possible cirrhosis

Answer 27

Jaundice

Question 28

How is PBC treated

Answer 28

UDCA: cytoprotectvie effect, inhibits absorption of toxic bile salts, improvement in liver biochemistry, improved survival free of transplant

Supportive care: treat pruritis, vitamin deficiencies, liver transplant once ESLD