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

Laboratory Testing for Primary Biliary Cholangitis (PBC)

For diagnosing PBC, you must obtain antimitochondrial antibodies (AMA) and alkaline phosphatase (ALP), with AMA being mandatory in all adults with chronic intrahepatic cholestasis. 1

Essential Diagnostic Laboratory Tests

Core Serologic Testing

• Antimitochondrial antibodies (AMA) are the diagnostic hallmark, detected in >90% of PBC patients with specificity >95%. 1
• AMA is 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 as an alternative. 1
• In AMA-negative patients, specific antinuclear antibodies (ANA) including anti-Sp100 and anti-gp210 show >95% specificity for PBC and serve as diagnostic markers (found in at least 30% of PBC sera). 1

Core Biochemical Testing

• Alkaline phosphatase (ALP) - elevation of liver-origin ALP for at least 6 months is a key diagnostic criterion. 1
• Gamma-glutamyl transpeptidase (GGT) - raised in PBC and should be performed to confirm ALP elevation is of hepatobiliary origin, particularly in post-menopausal women who may have bone-derived ALP from osteoporosis. 1
• Serum aminotransferases (ALT, AST) - can be elevated but are not diagnostic. 1
• Conjugated bilirubin - can be elevated but is not diagnostic; total bilirubin elevations indicate more advanced disease and poorer prognosis. 1

Additional Laboratory Tests for Disease Assessment

Immunologic and Metabolic Markers

• Immunoglobulin M (IgM) - typically elevated in PBC patients. 1 In treatment-naive patients with positive AMA but normal ALP, baseline IgM >0.773 × ULN strongly suggests PBC diagnosis and may indicate need for liver biopsy. 2
• Serum cholesterol - commonly elevated as in other cholestatic conditions. 1
• Prothrombin time and serum albumin - alterations observed only in advanced disease, serving as markers of hepatic synthetic function. 1

Additional Autoantibodies to Exclude Overlap Syndromes

While the provided evidence focuses on PSC rather than PBC, measurement of antinuclear antibodies (ANA), smooth muscle antibodies (SMA), and total immunoglobulins should be performed when positive results might suggest alternative diagnoses or overlap/variant syndromes. 3

Special Clinical Scenarios

Patients with Normal ALP

• Patients with normal ALP and GGT but serological stigmata of PBC (positive AMA or PBC-specific ANA) should be reassessed clinically and biochemically at annual intervals. 1
• GGT may serve as a biomarker in PBC patients with normal baseline ALP levels, showing significant decrease after ursodeoxycholic acid treatment. 4
• In these patients, baseline IgM >0.773 × ULN and age >42 years are factors strongly suggesting PBC diagnosis and need for liver biopsy. 2
• Dynamic monitoring of GGT and IgM may be helpful in evaluating therapeutic responses in patients receiving ursodeoxycholic acid. 2

When Liver Biopsy is Indicated

• Liver biopsy should be considered in patients with otherwise unexplained intrahepatic cholestasis and negative AMA test. 1
• When available, genetic testing for ABCB4 (encoding the canalicular phospholipid export pump) should be considered in AMA-negative patients with biopsy findings compatible with PBC. 1

Common Pitfalls to Avoid

• Do not assume elevated ALP is hepatic in origin - ALP may originate from bone rather than liver, necessitating GGT measurement or ALP isoenzyme fractionation for accurate interpretation, especially in post-menopausal women. 1
• Do not dismiss patients with normal ALP - a high proportion of AMA-positive patients with normal ALP levels have PBC on biopsy, and current guidelines do not cover the full extent of PBC presentation. 4
• Do not overlook AMA-negative disease - PBC-specific ANA (anti-Sp100, anti-gp210) can establish diagnosis in AMA-negative patients. 1