Primary Biliary Cholangitis

Diagnostic Criteria

• The diagnosis of primary biliary cholangitis (PBC) can be established with confidence through a combination of abnormal liver tests (elevation of hepatic alkaline phosphatase for at least 6 months) and the presence of antimitochondrial antibodies (AMA) in serum (≥1:40), as recommended by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases 1
• A cholestatic pattern, characterized by alkaline phosphatase >2 times the upper limit of normal (ULN) and gamma-glutamyl transferase (GGT) >5 times ULN, is indicative of PBC 1
• A diagnostic titer of ≥1:40 by immunofluorescence for AMA is recommended, with anti-AMA-M2 (anti-PDC-E2) as a useful alternative if available 1
• Antinuclear antibodies (ANA) are present in approximately 30% of PBC patients, with specific patterns (anti-Sp100, anti-gp210) having high diagnostic value (>95% specificity) but low sensitivity, and anti-gp210 can be found in 50% of AMA-negative patients 1, 2

Evaluation and Staging

• Initial evaluation should include liver function tests showing a cholestatic pattern (elevated AP and GGT) and abdominal ultrasound to exclude extrahepatic cholestasis, as suggested by the European Association for the Study of the Liver 2, 1
• Liver biopsy is no longer considered mandatory for diagnosis in patients with a cholestatic enzyme pattern and positive AMA, but is useful for evaluating disease activity and staging 1
• Histological characteristics of PBC include florid duct lesions with granuloma formation and histological staging (1-4) based on the degree of ductal damage, inflammation, and fibrosis 1

Complications and Advanced Disease

• Evidence of portal hypertension, such as thrombocytopenia, splenomegalia, and varices, is a significant complication of PBC 3
• Patients with bilirubin >50 μmol/L or evidence of decompensated liver disease should be considered for liver transplantation 3
• Non-invasive methods, such as elastography (FibroScan) and serum fibrosis markers (e.g. ELF test), can be used to assess fibrosis and disease severity 3
• The Mayo Risk Score is the most commonly used prognostic system, as recommended by the European Association for the Study of the Liver 2
• Bilirubin is a primary prognostic factor, with elevation indicating advanced disease, and alkaline phosphatase response to treatment is a key prognostic indicator, as suggested by the American College of Gastroenterology 3

Special Considerations

• Up to 40% of patients are asymptomatic at diagnosis, and the disease is frequently associated with other autoimmune disorders, such as Sjögren's syndrome, scleroderma, and Raynaud's phenomenon, according to the European Association for the Study of the Liver and the American College of Gastroenterology 2, 3
• Overlap syndromes, such as PBC-autoimmune hepatitis overlap, should be considered when aminotransferases are disproportionately elevated, and secondary causes of cholestasis, such as medications and biliary obstruction, should always be excluded, with distinguishing PBC from primary sclerosing cholangitis (PSC) requiring cholangiography for diagnosis 1, 4, 5