What laboratory tests are recommended for the diagnosis of Primary Sclerosing Cholangitis (PSC)?

Laboratory Tests for Diagnosis of Primary Sclerosing Cholangitis (PSC)

The diagnosis of PSC requires elevated serum markers of cholestasis as the primary laboratory finding, along with characteristic cholangiographic features on imaging and exclusion of secondary causes of sclerosing cholangitis. 1

Core Laboratory Tests

Essential Laboratory Tests

• Cholestatic liver enzymes:
  • Alkaline phosphatase (ALP) - typically elevated
  • Gamma-glutamyl transferase (GGT) - especially important for pediatric patients 2
  • Serum bilirubin - may be normal or elevated

Additional Laboratory Tests to Exclude Other Causes

• Complete liver biochemistry panel:

  • Transaminases (ALT, AST)
  • Albumin
  • Prothrombin time
  • Platelet count

• Immunological markers:

  • Serum IgG4 levels - to exclude IgG4-related sclerosing cholangitis 1
  • Total immunoglobulins and immunoglobulin subsets
  • Autoantibodies (ANA, SMA, p-ANCA) - not diagnostic for PSC but may be present 1

• Tests to exclude secondary causes:

  • HIV antibodies
  • Serum angiotensin converting enzyme
  • Antimitochondrial antibodies (AMA) - to exclude primary biliary cholangitis

Important Diagnostic Considerations

1. Autoantibodies should not be used to diagnose or risk-stratify PSC patients (strong recommendation, Level of Evidence 4) 1

2. Serum IgG4 determination is suggested in every adult patient with large duct sclerosing cholangitis at the time of diagnosis (weak recommendation, Level of Evidence 3) 1

   • Elevated IgG4 may indicate IgG4-related sclerosing cholangitis rather than PSC
   • In cases where serum IgG4 is less than 2× upper limit of normal, the ratio of IgG4/IgG1 >0.24 is indicative of IgG4-associated cholangitis 3

3. Laboratory tests alone are insufficient for diagnosis:

   • Cholestatic biochemistry must be accompanied by characteristic findings on cholangiography 1
   • MRCP is the preferred imaging modality (strong recommendation, high quality evidence) 1

Risk Assessment and Monitoring

After diagnosis, risk assessment should include:

• Standard biochemistry (bilirubin, albumin, ALP, ALT, platelets, prothrombin time) 1
• Clinical review and standard liver tests every 6-12 months depending on risk stratification 1

Common Pitfalls

1. Relying solely on laboratory tests for diagnosis:

   • Laboratory abnormalities in PSC are non-specific and must be correlated with imaging
   • Up to 56.6% of patients may be asymptomatic at diagnosis with only abnormal laboratory tests 4

2. Missing small duct PSC:

   • In patients with cholestatic liver enzymes but normal cholangiography, liver biopsy is necessary to diagnose small duct PSC 1

3. Overlooking overlap syndromes:

   • Consider liver biopsy in patients with markedly elevated transaminases, high IgG levels, and positive autoantibodies compatible with autoimmune hepatitis 1

4. Misinterpreting CA 19-9 levels:

   • CA 19-9 has unsatisfactory sensitivity (14%) and positive predictive value (67%) for cholangiocarcinoma in PSC patients and is not recommended for surveillance purposes 1

Remember that the diagnosis of PSC requires a combination of laboratory findings, imaging results, and exclusion of secondary causes. Laboratory tests alone, while essential, are not sufficient for definitive diagnosis.