What are the diagnostic criteria and management options for primary sclerosing cholangitis (PSC)?

Diagnosis of Primary Sclerosing Cholangitis

The diagnosis of PSC requires cholestatic liver biochemistry with typical cholangiographic features showing multifocal bile duct strictures and segmental dilatations on MRCP, after excluding secondary causes of sclerosing cholangitis. 1

Diagnostic Criteria

Essential Components

• Cholestatic biochemical profile (elevated alkaline phosphatase and gamma-glutamyl transferase) is the biochemical hallmark 1

• MRCP is the principal imaging modality for diagnosis, with sensitivity of 86% and specificity of 94% for detecting PSC 1, 2

  • Shows characteristic "beading" appearance from multifocal strictures and segmental dilatations 1
  • ERCP should be reserved only for patients requiring tissue acquisition or therapeutic intervention 1

• Exclusion of secondary sclerosing cholangitis is mandatory before confirming PSC diagnosis 1

  • Secondary causes include choledocholithiasis, surgical trauma, intra-arterial chemotherapy, recurrent pancreatitis 1

Additional Diagnostic Testing

• Measure serum IgG4 levels in all patients with possible PSC to exclude IgG4-associated sclerosing cholangitis, which responds to corticosteroids 1

  • Elevated IgG4 (≥140 mg/dL) occurs in approximately 9% of PSC patients and may indicate more aggressive disease 1

• Perform colonoscopy with colonic biopsies in all PSC patients to assess for inflammatory bowel disease, present in 60-80% of cases 1

• Liver biopsy is NOT routinely recommended when cholangiography shows typical PSC findings 1

  • However, biopsy IS indicated when: 1
    • Cholangiography is normal (to diagnose small duct PSC)
    • Aminotransferases are disproportionately elevated (to exclude PSC-autoimmune hepatitis overlap syndrome)

Important Diagnostic Pitfalls

MRCP has limitations in early disease and cirrhosis. MRCP may be less sensitive than ERCP in detecting early PSC changes and has reduced specificity in patients with established cirrhosis 1. Despite this, the risks of ERCP (pancreatitis, cholangitis, perforation) outweigh benefits for diagnostic purposes alone 1.

Distinguish IgG4-associated cholangitis from PSC. Long biliary strictures with prestenotic dilatations and low common bile duct strictures suggest IgG4-SC rather than PSC, which typically shows beading and peripheral duct pruning 1. This distinction is critical because IgG4-SC responds to corticosteroids while PSC does not 1.

Management Approach

Initial Assessment and Monitoring

• Screen for cirrhosis and portal hypertension with endoscopy for esophageal varices when evidence of advanced disease exists 1

• Assess for osteoporosis in all PSC patients, as bone disease is common 1

• Evaluate for fat-soluble vitamin deficiency with low threshold for empirical replacement in advanced disease 1

Symptom Management

• For pruritus: Cholestyramine is first-line treatment; rifampicin and naltrexone are second-line options 1

• For fatigue: Actively seek and treat alternative causes rather than attributing all fatigue to PSC 1

Surveillance and Complications

• Perform non-invasive imaging (MRCP, dynamic liver MRI, or contrast CT) when patients develop new/changing symptoms or evolving laboratory abnormalities 1

• ERCP should only be performed after expert multidisciplinary assessment to justify endoscopic intervention 1

  • When ERCP is done for dominant strictures, pathological sampling is mandatory to exclude cholangiocarcinoma 1
  • Biliary dilatation is preferred over stent insertion for dominant strictures 1

• Prophylactic antibiotics are required for all patients with suspected PSC undergoing ERCP 1

• CA19-9 has low diagnostic accuracy and routine measurement is not recommended for cholangiocarcinoma surveillance 1

  • When cholangiocarcinoma is suspected clinically, refer for specialist multidisciplinary meeting review 1
  • Contrast-enhanced cross-sectional imaging is the initial preferred investigation 1

Referral and Advanced Care

• Refer patients with symptomatic, evolving, or complex disease for expert multidisciplinary assessment 1

  • Early, stable disease can be managed in general clinics 1

• Liver transplantation is the only definitive treatment for end-stage PSC 1

  • Assess eligibility and refer according to national guidelines when appropriate 1
  • Recurrence after transplantation occurs in up to 20% of patients 3

• Consider referral to centers participating in clinical trials for eligible patients, as no medical therapy has proven effective in altering disease progression 1, 3