What labs should be drawn for the diagnosis and management of Primary Biliary Cholangitis (PBC)?

Laboratory Testing for Primary Biliary Cholangitis (PBC)

The diagnosis of PBC requires testing for antimitochondrial antibodies (AMA) combined with alkaline phosphatase (ALP) measurement, with AMA being mandatory in all adults with chronic intrahepatic cholestasis. 1

Essential Diagnostic Laboratory Tests

Primary Serological Markers

• Antimitochondrial antibodies (AMA) at titre ≥1:40 by immunofluorescence—this is the diagnostic hallmark of PBC, detected in >90% of patients with specificity >95% 2, 1, 3
• Anti-AMA-M2 (anti-PDC-E2) immunoenzymatic assays with recombinant proteins may be used as an alternative to standard AMA testing, offering higher sensitivity and specificity 2, 1

Cholestatic Biochemical Markers

• Alkaline phosphatase (ALP)—elevated for at least 6 months is a key diagnostic criterion; must confirm hepatobiliary origin rather than bone-derived 1
• Gamma-glutamyl transpeptidase (GGT)—should be measured to confirm ALP elevation is of hepatobiliary origin, particularly important in post-menopausal women who may have bone-derived ALP from osteoporosis 1
• ALP fractionation or GGT measurement is essential when ALP elevation is present, as ALP may originate from bone rather than liver 1

Alternative Serological Markers (for AMA-negative patients)

• Antinuclear antibodies (ANA) including anti-Sp100 and anti-gp210—show high specificity for PBC (>95%) and can serve as diagnostic markers when AMA is negative, though sensitivity is low (found in at least 30% of PBC sera) 2, 1
• ANA testing is particularly important as ANA (especially ANA centromere pattern) may be the highest positive autoantibody in AMA-negative early-stage PBC 4

Additional Biochemical Tests for Disease Assessment

Hepatic Function and Synthetic Markers

• Serum aminotransferases (ALT, AST)—can be elevated but are not diagnostic; alterations serve as markers only in advanced disease 1
• Total and conjugated bilirubin—elevations indicate more advanced disease and poorer prognosis 1
• Serum albumin—decreases with disease progression and serves as a marker of hepatic synthetic function 1
• Prothrombin time—alterations observed only in advanced disease as a marker of hepatic synthetic function 1

Immunological and Lipid Markers

• Immunoglobulin M (IgM)—typically elevated in PBC patients 2, 1
• Immunoglobulin G (IgG)—when disproportionately elevated along with transaminases, may indicate overlap syndrome requiring liver biopsy 2, 3
• Serum cholesterol—commonly elevated as in other cholestatic conditions 2, 1

Special Considerations and Monitoring

For AMA-Negative Patients

• When AMA and AMA-M2 are negative, test for ANA with specific patterns (particularly centromere pattern), anti-Sp100, and anti-gp210 4, 5
• Consider genetic testing for ABCB4 (encoding the canalicular phospholipid export pump) in AMA-negative patients with biopsy findings compatible with PBC 1
• Liver biopsy is needed for diagnosis in the absence of PBC-specific antibodies 2, 3

For Patients with Normal ALP

• Patients with normal ALP and GGT but positive PBC serology should be reassessed clinically and biochemically at annual intervals 1
• In patients with normal ALP but positive AMA, GGT may be significantly elevated and can serve as a biomarker, particularly when monitoring treatment response 6

For Suspected Overlap Syndrome

• In patients with ANA or anti-smooth muscle antibody titers >1:80 or IgG >2× normal combined with ALT <5× ULN, perform liver biopsy to rule out overlap disease 3
• Liver biopsy may be helpful when there are disproportionately elevated serum transaminases and/or serum IgG levels to identify additional or alternative processes 2, 3

Common Pitfalls to Avoid

• Do not assume elevated ALP is hepatobiliary in origin—always confirm with GGT or ALP fractionation, especially in post-menopausal women 1
• Do not exclude PBC diagnosis based on normal ALP alone—up to 29% of early-stage PBC patients may have normal ALP levels, but GGT is often significantly elevated 4, 6
• Do not overlook ANA testing in AMA-negative patients—PBC-specific ANA patterns (anti-Sp100, anti-gp210, centromere) can establish diagnosis even without AMA 2, 1, 4
• Do not delay liver biopsy in AMA-negative patients with cholestasis—biopsy is essential for diagnosis when PBC-specific antibodies are absent 2, 3

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