What laboratory tests are recommended for the diagnosis and management of Primary Biliary Cholangitis (PBC)?

Laboratory Tests for Primary Biliary Cholangitis (PBC)

Testing for serum antimitochondrial antibodies (AMA) is mandatory in adults with chronic intrahepatic cholestasis, as AMA is the diagnostic hallmark of PBC, detected in over 90% of patients with specificity greater than 95%. 1

Essential Diagnostic Laboratory Tests

Biochemical Markers (First-Line)

• Alkaline phosphatase (ALP): Elevated ALP of hepatic origin for at least 6 months is required for diagnosis, present in approximately 75% of PBC patients 1, 2
• Gamma-glutamyl transferase (GGT): Raised in PBC and useful to confirm hepatic origin of elevated ALP, particularly important in postmenopausal women where ALP can originate from bone 1, 2
• Aminotransferases (ALT, AST): Can be elevated but are not diagnostic; typically normal or only mildly elevated in early disease 1, 2
• Conjugated bilirubin: May be elevated but not diagnostic; normal bilirubin is typical at diagnosis in the majority of patients 1, 2
• Total bilirubin: Observed to be elevated only in advanced disease; alterations indicate disease progression 1

Immunological Markers (Mandatory)

• Antimitochondrial antibodies (AMA): Positive at titer ≥1:40 in over 90% of PBC patients; considered positive by immunofluorescence at this threshold 1
• Anti-AMA-M2 (anti-PDC-E2): When available, this immunoenzymatic assay with recombinant proteins raises sensitivity and specificity; useful alternative to standard AMA testing 1
• Antinuclear antibodies (ANA): Found in at least 30% of PBC sera; specific patterns include anti-Sp100 and anti-gp210 (appearing as multiple nuclear dots and perinuclear rims) with specificity >95% for PBC when AMA is absent 1

Additional Markers for Disease Assessment

• Immunoglobulin M (IgM): Typically elevated in PBC patients 1
• Serum cholesterol: Commonly elevated as in other cholestatic conditions 1
• Prothrombin time: Alterations observed only in advanced disease 1
• Serum albumin: Alterations observed only in advanced disease; low albumin indicates impaired hepatic synthetic function requiring hepatology referral 1, 3

Laboratory Tests for Monitoring and Management

Routine Monitoring Parameters

• ALP and bilirubin levels: Monitor as surrogate endpoints for disease progression and treatment response; falling ALP (normalization or <1.5× upper limit of normal) stratifies for improved outcomes 2, 4
• Total and conjugated bilirubin: Patients with high levels or alkaline phosphatase >1.5-fold the upper limit of normal should be considered for second-line therapy 5
• Liver biochemical tests: Routinely monitor for progression of PBC and hepatic adverse reactions 4

Assessment of Treatment Response (at 12 months on ursodeoxycholic acid)

The composite response criteria include: 4

• ALP <1.67× upper limit of normal
• Total bilirubin ≤ upper limit of normal
• ALP decrease of at least 15%

Advanced Disease Indicators

• Elevated prothrombin time or international normalized ratio: Indicator of cirrhosis or portal hypertension 1
• Low platelets: Indicator of cirrhosis or portal hypertension 1
• AST>ALT ratio: May indicate cirrhosis and poor prognosis 1

Differential Diagnosis Testing

When AMA is negative, consider: 1

• Liver biopsy: Should be considered in patients with otherwise unexplained intrahepatic cholestasis and negative AMA test
• ABCB4 genetic testing: When available, should be considered in patients with negative AMA test and biopsy findings compatible with PBC
• Additional autoantibodies: Measure ANA, smooth muscle antibodies (SMA), HIV antibodies, serum angiotensin converting enzyme, and IgG4 to exclude alternative diagnoses or overlap syndromes 1

Common Pitfalls to Avoid

• Do not rely solely on ALP elevation: Approximately 29% of early-stage PBC patients have normal ALP levels; GGT may be more robustly elevated 6
• Do not dismiss normal aminotransferases: In early-stage PBC, 50% of patients have normal ALT and 37.5% have normal AST 6
• Confirm hepatic origin of ALP: Use GGT or ALP isoenzyme fractionation, especially in postmenopausal women where bone can be the source 2
• Consider ANA patterns when AMA-negative: ANA centromere pattern has high specificity for PBC when AMA and AMA-M2 are negative 6