What labs are used to diagnose and manage Primary Biliary Cholangitis (PBC)?

Laboratory Testing for Primary Biliary Cholangitis (PBC)

Essential Diagnostic Labs

The diagnosis of PBC requires two key laboratory tests: antimitochondrial antibodies (AMA) and alkaline phosphatase (ALP), with AMA being mandatory in all adults with chronic intrahepatic cholestasis. 1

Core Diagnostic Tests

• Antimitochondrial antibodies (AMA) are the diagnostic hallmark, detected in >90% of PBC patients with specificity >95%, and are considered positive at a titre ≥1:40 by immunofluorescence 1
• Anti-AMA-M2 (anti-PDC-E2) immunoenzymatic assays with recombinant proteins offer higher sensitivity and specificity and may be used as an alternative to standard AMA testing 2, 1
• Alkaline phosphatase (ALP) of liver origin must be elevated for at least 6 months as a key diagnostic criterion 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

AMA-Negative PBC Testing

When AMA is negative but PBC is suspected, specific antinuclear antibodies become critical:

• Anti-Sp100 and anti-gp210 show high specificity for PBC (>95%) and can serve as diagnostic markers when AMA is absent, though sensitivity is low (found in at least 30% of PBC sera) 2, 1
• ANA centromere pattern has the highest positivity rate among ANA patterns in early-stage AMA-negative PBC (38.5%) 3
• Liver biopsy should be considered in patients with otherwise unexplained intrahepatic cholestasis and negative AMA test 1
• ABCB4 genetic testing (encoding the canalicular phospholipid export pump) should be considered when available in AMA-negative patients with biopsy findings compatible with PBC 1

Biochemical Markers for Disease Assessment

Standard Liver Panel

• Serum aminotransferases (ALT, AST) can be elevated but are not diagnostic; in early-stage PBC, 50% have normal ALT and 37.5% have normal AST 3
• Conjugated bilirubin should be measured, with elevations indicating more advanced disease and poorer prognosis 1
• Serum albumin tends to decrease with disease progression and serves as a marker of hepatic synthetic function 1
• Prothrombin time/INR alterations are observed only in advanced disease 1

Cholestatic and Immunologic Markers

• Immunoglobulin M (IgM) levels are typically elevated in PBC patients 2, 1
• Serum cholesterol is commonly elevated as in other cholestatic conditions 2
• Total bilirubin is a critical prognostic marker, with elevations indicating more advanced disease 1

Critical Diagnostic Pitfalls

Normal ALP Does Not Exclude PBC

A significant proportion of AMA-positive patients with normal ALP levels have histologically confirmed PBC:

• 29.2% of early-stage PBC patients have normal ALP levels 3
• 80% of AMA-positive patients with normal ALP who underwent liver biopsy had histology typical for, consistent with, or suggestive of PBC 4
• GGT is more robustly elevated than ALP in early disease, with 29.2% of early-stage patients having GGT levels >10 times the upper limit of normal despite normal or mildly elevated ALP 3

Pattern Recognition in Early Disease

In early-stage PBC with normal or mildly elevated standard markers:

• Significantly elevated GGT with normal or minimally elevated ALP should raise suspicion for early PBC 3, 4
• ANA positivity (particularly centromere pattern) when AMA/AMA-M2 are negative may indicate early PBC and warrants further investigation 3
• GGT can serve as a biomarker for monitoring treatment response in PBC patients with normal baseline ALP levels, showing significant decrease after ursodeoxycholic acid treatment 4

Monitoring and Follow-Up Labs

For Established PBC Patients

• ALP normalization or <1.5 × upper limit of normal serves as a stratifier for improved outcomes and should be the therapeutic goal 2
• Patients with normal ALP and GGT but serological stigmata of PBC should be reassessed clinically and biochemically at annual intervals 1

When to Consider Overlap Syndrome

• Disproportionately elevated serum transaminases and/or serum IgG levels in PBC patients may indicate additional or alternative processes, particularly AIH-PBC overlap syndrome requiring liver biopsy 2, 5
• Moderate-to-severe hepatitis on biopsy warrants consideration of combined immunosuppressants 5