PSC, PBC, & Cholangiocarcinoma Flashcards
Primary Sclerosing cholangitis (PSC): definition and epidemiology
Definition:
• Progressive disease of cholestasis
• Bile duct injury (intra- and extra-hepatic)
• Characterized by inflammation, fibrosis, strictures
Etiology
• Caucasians
• Young men (M:F 2:1); usually before 45 years
• Relatively rare (1-6/100,000)
PSC associated with Inflammatory bowel disease
• 75% have ulcerative colitis
• 5% have Crohn’s
• 2.5-7.5% of ulcerative colitis patients have PSC
HLA association: HLA DRw52a (50% of PSC patients)
Primary Sclerosing cholangitis (PSC): pathogenesis
Autoimmune disease
• Elevated immunoglobulins and autoantibodies
• 80-90% have p-ANCA Abs (perinuclear antineutrophil cytoplasmic Abs)
• Circulating immune complexes and Abs cross-react with biliary and colonic epithelium
Genetic factors
• Increased in 1st degree relatives
Inflammatory/infectious reaction
• Bacteria from portal circulation?
• Ischemic disease
Primary Sclerosing cholangitis (PSC): pathology
- ERCP = beaded appearance
* Biopsy = “onion skinning” but in only 10% of patients
Primary Sclerosing cholangitis (PSC): clinical presentation
- Asymptomatic (~10%)
- Fatigue, weight loss, abdominal pain
- Pruritis (25-60%)
- Episodic Jaundice (30–70%)
- Acute cholangitis = relatively rare (5-25%)
- Advanced liver disease
- Ascites, variceal bleeding = rare (2-15%)
Primary Sclerosing cholangitis (PSC): diagnosis
- Alkalline phosphatase = 2x normal (reflects bile flow)
- Elevated transaminases, bilirubin, prothrombin time, low albumin as disease progresses
ERCP = gold standard
• Multifocal strictures with intervening normal or dilated ducts
• “Beaded appearance”
Primary Sclerosing cholangitis (PSC): prognosis
- Poor prognosis if have HLA-DR4
- Natural history = variable
- Generally slow progression to secondary biliary cirrhosis, portal HT, liver failure
3 possible biliary complications:
• Dominant stricture
• Stone
• Cholangiocarcinoma
Median survival = 12 years
• At 5 years: 75% show progressive disease with 15% liver failure
• 10-30% will develop cholangiocarcinoma
Primary Sclerosing cholangitis (PSC): treatment
Supportive
• NO intervention has shown to prevent progression
• No medical therapy
Endoscopic treatment
• Remove stones
• Stent dilate dominant strictures = helps with complications
• May delay time to transplantation and improve survival time
Liver transplantation
• Improved survival
• 5 year survival >75% (before transplant; was only 60-70%)
Primary Biliary Cirrhosis (PBC): definition and epidemiology
Definition:
• Progressive chronic cholestatic autoimmune disease
• Affects the small intrahepatic ducts
Etiology
• 90% women
• Caucasian
• 6th -7th decade
Primary Biliary Cirrhosis (PBC): pathogenesis
Environmental trigger (infection, chemical, toxin) in susceptible individual → immune response
Autoimmune (T cell) destruction of small bile duct epithelial cells in lobule
• Chronic damage/destruction → obstruction of bile flow and cholestasis → hepatocyte injury, scarring and accumulation of bile acids
• Potential cirrhosis and liver failure
Associated with immunologic abnormalities:
• Presence of antimitochondrial Abs (AMA)
• IgM hypergammaglobulineia
• Circulating immune complexes
Primary Biliary Cirrhosis (PBC): pathology
- Patchy destruction of intrahepatic bile ducts
- Mononuclear inflammatory infiltrate
- Granulomas support diagnosis
Primary Biliary Cirrhosis (PBC): clinical presentation
- 50% asymptomatic
- Diagnosed by abnormal screening test
- Fatigue (>80%)
- Pruritis (50%)
- Jaundice = sign of disease progression
- Bile acid depletion → steatorrhea, elevated cholesterol, vitamin deficiencies, osteomalacia & osteoporosis (secondary to vitamin D malabsorption)
Late findings: Liver sequelae Hepatomegaly/splenomegaly Cirrhosis/portal HT o Ascities o Esophageal varices and bleeding o Increased risk of hepatocellular carcinoma
Associated with other autoimmune diseases (ex: Sjorgens’s syndrome, scleroderma, autoimmune thyroiditis)
Primary Biliary Cirrhosis (PBC): diagnosis
- Elevated alkaline phosphatase
- Elevated bilirubin = suggests progressive disease
- Positive AMA, hypergammaglobulinemia
- Liver biopsy = confirm
Primary Biliary Cirrhosis (PBC): prognosis
Variable with wide spectrum
Generally slowly progressive disease and patients can be asymptomatic for years
• 40% of asymptomatic patients will develop symptoms in 5-7 years
• Asymptomatic = normal life span
• Symptomatic = median 11-12 year survival (once become symptomatic = becomes progressive)
Bilirubin greatest predictor of survival
• Bilirubin >10 or cirrhosis = survival <2 years without transplant
Primary Biliary Cirrhosis (PBC): treatment
Ursodeoxycholic acid (UDCA)
Cytoprotective and choleretic (improves flow) affect
o Inhibits absorption of toxic bile salts
o Replaces endogenous bile salts
o Stabilizes hepatocyte membranes against toxic bile salts
Clear improvement in liver biochemistries and survival free of liver transplantation
Improves outcome = every PBC patient should be on UDCA
Symptomatic treatment:
• Pruritus: antihistamines, cholestyramine, rifampin, phenobarbital
• Vitamin deficiencies = supplement
Liver transplant for ESLD
• PBC patients have highest post-transplant survival
Cholangiocarcinoma: definition
Cancer of bile duct; can occur anywhere along biliary tree:
o Intrahepatic mass
o Bifurcation/Hilum (Klatskin tumor)
o Extrahepatic
