primary sclerosing cholangitis (PSC)

Introduction

Recurrent or persistent obstructive jaundice.

Etiology

• autoimmune mechanism has been postulated
  • IgG4 disease associated with autoimmune pancreatitis
• frequently occurs in association with ulcerative colitis*

* 80-85% of patients with with primary sclerosing cholangitis have inflammatory bowel disease (generally ulcerative colitis), but only 4% of patients with ulcerative colitis have primary sclerosing cholangitis

Epidemiology

• most commonly seen in young men

Pathology

• inflammation & obliterative fibrosis of the bile ducts, intrahepatic & extrahepatic
• generally progresses to cholestasis, secondary biliary cirrhosis, portal hypertension, hepatic failure
• concentric fibrosis of bile ductules

Clinical manifestations

• frequently asymptomatic
• progressive fatigue
• pruritus
• jaundice
• intermittent or fluctuating symptoms
  • unlikely to manifest acutely
• bacterial cholangitis is uncommon without history of prior biliary tract surgery or instrumentation
• 85% of patients have inflammatory bowel disease (generally ulcerative colitis)
  • hematochezia

Laboratory

• increased serum alkaline phosphatase
• abnormal liver function tests
  • increased serum bilirubin & serum conjugated bilirubin
  • increased serum AST
  • increased serum ALT
  • increased serum GGT
• IgG4 in serum may be increased (IgG4 disease)
  • does not preclude 1st line ERCP
• CA 19-9 in serum for cholangiocarcinoma surveillance
• liver biopsy (diagnostic for intrahepatic bile duct disease)
• complete blood count (CBC)
  • hematochezia due to association with ulcerative colitis

Diagnostic procedures

• MRCP shows gall bladder & bile duct
  • 1st line procedure
  • establishes diagnosis ('string of beads')
  • annually for cholangiocarcinoma surveillance
• ERCP combined with cholangiography, expensive
  • diagnostic if extrahepatic bile duct disease
  • shows short strictures of bile ducts with intervening segments of normal or slightly dilated ducts (beaded appearance, "beads on a string ")
  • facilitates diagnosis of cholangiocarcinoma
• if ERCP is unsuccessful, percutaneous cholangiography should be attempted
• colonoscopy at the time of diagnosis & every 1-2 years for survelliance
• patients with inflammatory bowel disease should have surveillance colonoscopy every year

Radiology

• ultrasound (screening)
  • screening patients with cirrhosis for hepatocellular carcinoma with ultrasound every 6 months
• magnetic resonance imaging (MRI) as good as ERCP in patients with cholestatic biochemical profiles

Complications

• bile duct stricture
• cholangiocarcinoma 15% lifetime risk
  • higher risk for bile duct cancer
  • generally develops within the 1st few years of PSC diagnosis
• higher risk for gall bladder cancer
• inflammatory bowel disease (85%)
  • rectal sparing, mild pancolitis, backwash ileitis
  • elevated risk of pouchitis after colectomy
• increased risk for colorectal cancer
• highest mortality among autoimmune liver diseases

• disease interaction(s) of inflammatory bowel disease with primary sclerosing cholangitis

Differential diagnosis

• AIDS cholangiopathy
  • CD4 count < 100/uL
  • due to CMV or Cryptosporidium
• ischemic cholangiopathy

Management

• treatment is generally supportive
  • cholestyramine to relieve pruritus
  • vitamin supplements
    • vitamins A, D, & K malaborption may occur
  • ursodiol to prevent gallstone formation
  • consider obeticholic acid (start 5 mg/day) +/- fibrate if response to ursodiol at 12 months is inadequate (use with caution in patients with decompensated liver disease)
  • glucocorticoids for associated autoimmune pancreatitis with elevated IgG4 (IgG4 disease)
• proctocolectomy in patients with ulcerative colitis has no effect on development of primary sclerosing cholangitis
• percutaneous or endoscopic balloon dilatation of bile duct strictures may offer palliation (pain, fever)
• surgery for strictures not amenable to endoscopic or percutaneous intervention in non-cirrhotic patients
• antibiotics
  • antibiotic treatment of superimposed infection
  • prophylactic long-term antibiotics might be beneficial for patients with recurrent bacterial cholangitis
• many patients require liver transplantation
  • only effective treatment

More general terms

• cholangitis

Additional terms

• primary biliary cirrhosis; primary biliary cholangitis
• ulcerative colitis (UC)

Patient information

primary sclerosing cholangitis patient information