What are PBC (Primary Biliary Cholangitis) markers?

Primary Biliary Cholangitis (PBC) Markers

The diagnostic hallmark of PBC is the presence of antimitochondrial antibodies (AMA), which are detected in serum of more than 90% of affected individuals with a specificity greater than 95%. 1

Biochemical Markers

PBC is characterized by a cholestatic pattern of liver enzymes:

• Alkaline Phosphatase (ALP): Typically elevated, a sensitive marker for diagnosis but not specific. In early-stage PBC, approximately 29% of patients may have normal ALP levels 2
• Gamma-Glutamyl Transferase (GGT): Usually elevated, often more robustly than ALP. In early-stage PBC, GGT can be >10 times the upper limit of normal in 29.2% of patients 2
• Aminotransferases (ALT, AST): Often mildly elevated but not diagnostic. In early-stage PBC, 50% of patients may have normal ALT and 37.5% may have normal AST 2
• Bilirubin: Usually normal in early disease; elevation indicates advanced disease and poor prognosis 1
• Immunoglobulin M (IgM): Typically elevated in PBC patients 1
• Serum Cholesterol: Commonly elevated as in other cholestatic conditions 1

Immunological Markers

1. Antimitochondrial Antibodies (AMA):

   • Present in >90% of PBC patients 1
   • Specificity >95% for PBC 1
   • AMA reactivity is classically studied by immunofluorescence and considered positive at a titer ≥1:40 1
   • Anti-AMA-M2 (anti-PDC-E2) may be used as an alternative if available 1

2. Antinuclear Antibodies (ANA):

   • Found in at least 30% of PBC sera 1
   • Specific ANA patterns highly associated with PBC include:
     • Anti-Sp100 (multiple nuclear dots pattern) - specificity >95% 1
     • Anti-gp210 (perinuclear rim pattern) - specificity >95% 1
   • These specific ANAs are valuable markers when AMA is negative 1

3. AMA-Negative PBC:

   • In AMA-negative cases with early-stage PBC, the most common autoantibody is ANA (92.3%) 2
   • ANA centromere pattern is the most common (38.5%) in AMA-negative early PBC 2
   • Novel biomarkers for AMA-negative cases include anti-kelch-like-12 and anti-hexokinase-1 antibodies 3

Diagnostic Approach

A diagnosis of PBC can be made with confidence based on:

1. Abnormal serum liver tests (elevation of ALP of liver origin for at least 6 months) AND
2. Presence of AMA (≥1:40) and/or AMA type M2 1

In AMA-negative cases, diagnosis may require:

• Liver biopsy showing characteristic features of florid bile duct lesions 1
• Testing for PBC-specific ANA (anti-Sp100, anti-gp210) 1

Clinical Pearls

• When AMA and AMA-M2 are negative, significantly elevated GGT (with or without normal ALP) plus positive ANA (particularly ANA centromere) may indicate early PBC 2
• Laboratory methods for antibody detection include immunofluorescence, enzyme-linked immunosorbent assay (ELISA), immunoblotting, and bead-based assays 3
• A liver biopsy should be considered in patients with otherwise unexplained intrahepatic cholestasis and a negative AMA test 1
• Genetic testing for ABCB4 (encoding the canalicular phospholipid export pump) should be considered in patients with negative AMA and biopsy findings compatible with PBC 1

Monitoring Markers

For patients diagnosed with PBC, monitoring should include:

• ALP levels - falling ALP (normalization or <1.5× upper limit of normal) is associated with improved outcomes 1
• Bilirubin - an important marker of disease progression and prognosis 1
• Albumin, prothrombin time/INR, and platelets - indicators of cirrhosis or portal hypertension 1

Early detection and treatment with ursodeoxycholic acid significantly improves outcomes, making accurate identification of these markers crucial for patient management 4, 5.