Primary sclerosing cholangitis (PSC)

Summary

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease characterized by inflammation and fibrosis of the intrahepatic and/or extrahepatic bile ducts. The condition predominantly affects young men and is strongly associated with inflammatory bowel disease (IBD), particularly ulcerative colitis. Patients may be asymptomatic or present with fatigue, pruritus, and jaundice. Diagnosis is confirmed by MRCP showing the characteristic "beads-on-a-string" appearance. Management is mainly supportive with liver transplantation being the only definitive treatment. Complications include cholangiocarcinoma, colon cancer, and cirrhosis.

Definition

• Chronic cholestatic liver disease characterized by inflammation, fibrosis, and stricturing of medium and large bile ducts
• Affects both intrahepatic and extrahepatic bile ducts
• Progressive disease leading to biliary cirrhosis and liver failure
• Up to 90% of patients have inflammatory bowel disease (IBD), especially ulcerative colitis

Epidemiology

• Age: Typically affects young adults (30-40 years)
• Gender: Male predominance (2:1 ratio)
• IBD association:
  • 70-90% of PSC patients have IBD (usually ulcerative colitis)
  • Conversely, only 5% of IBD patients develop PSC

Pathophysiology

• Primary process: Unknown etiology, likely autoimmune
  • Inflammatory destruction of bile ducts
  • Progressive fibrosis and stricturing
• Histologic findings:
  • "Onion-skin" fibrosis - ( image 1) concentric layers of connective tissue around bile ducts 
  • Fibrous obliteration of small bile ducts
  • Note: Biopsy often shows nonspecific findings
• Progression: Biliary obstruction → cholestasis → cirrhosis → liver failure

Clinical Features

• Early disease (often asymptomatic):
  • Incidental finding of elevated alkaline phosphatase
  • No symptoms in many patients
• Symptomatic disease:
  • Fatigue - most common symptom
  • Pruritus - due to bile salt accumulation
  • Jaundice - late finding
  • Right upper quadrant abdominal pain
  • Hepatomegaly
• Advanced disease:
  • Signs of cirrhosis (ascites, varices, encephalopathy)
  • Recurrent episodes of cholangitis

Diagnosis

• Laboratory findings:
  • Cholestatic pattern:
    • ↑↑ Alkaline phosphatase (most sensitive)
    • ↑ GGT
    • ↑ Bilirubin (later in disease)
    • Mild ↑ transaminases (AST/ALT)
  • Other findings:
    • Positive p-ANCA (perinuclear anti-neutrophil cytoplasmic antibodies) - not diagnostic
    • ↑ IgM levels
• Imaging - MRCP (Magnetic Resonance Cholangiopancreatography):
  • Gold standard for diagnosis
  • Shows characteristic "beads-on-a-string" appearance:  ( image 2)
  • Multiple segmental strictures
  • Alternating with normal or dilated segments
  • Affects both intrahepatic and extrahepatic ducts
• Other tests:
  • Ultrasound: Usually normal, may show bile duct thickening
  • ERCP: Reserved for therapeutic interventions (risk of cholangitis)
  • Liver biopsy: Not routinely needed, shows "onion-skin" fibrosis
  • Colonoscopy: Screen for IBD at diagnosis

Management

• No curative medical therapy - management is supportive
• Symptomatic treatment:
  • Pruritus:
    • First-line: Cholestyramine (bile acid sequestrant)
    • Alternatives: Rifampicin, naltrexone
  • Fat-soluble vitamin supplementation (A, D, E, K)
• Controversial therapies:
  • Ursodeoxycholic acid (UDCA):
    • Standard dose may improve liver enzymes
    • High dose increases mortality - avoid!
    • Does not improve survival
• Interventional management:
  • ERCP with balloon dilation for dominant strictures
  • Antibiotics for cholangitis episodes
• Definitive treatment:
  • Liver transplantation - only curative option
  • Median survival without transplant: 10-20 years from diagnosis

Complications

• Malignancy:
  • Cholangiocarcinoma (10-15% lifetime risk)
    • Screen with MRI/MRCP every 6 months
    • CA 19-9 may be elevated
  • Colon cancer (in patients with UC)
    • 5x higher risk than UC alone
    • Annual colonoscopy required
  • Hepatocellular carcinoma (if cirrhotic)
• Biliary complications:
  • Recurrent ascending cholangitis (fever + RUQ pain + jaundice)
  • Dominant strictures
  • Cholelithiasis
• Metabolic complications:
  • Fat-soluble vitamin deficiency (A, D, E, K)
  • Osteoporosis
  • Steatorrhea
• End-stage liver disease:
  • Cirrhosis
  • Portal hypertension
  • Liver failure

Differential Diagnosis

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