The Role of Laboratory Markers in Primary Biliary Cholangitis: A Clinical Review and a Case Report

BACKGROUND: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease characterized by marked clinical and serological heterogeneity. Although diagnosis is mainly based on antimitochondrial antibodies (AMAs) and alkaline phosphatase (ALP), non-classical presentations remain a relevant cause of diagnostic delay. In this context, laboratory medicine plays a pivotal role in both diagnosis and long-term disease management. METHODS: This manuscript represents a structured clinical review of laboratory biomarkers relevant to the diagnosis, monitoring, and prognostic stratification of PBC, integrated with a representative atypical case with long-term follow-up to illustrate the practical application of laboratory-driven diagnostic. RESULTS: The analysis confirms the central role of immunological and biochemical markers in treatment monitoring and prognostic assessment, while highlighting their limitations in selected clinical scenarios. The reported case, characterized by persistent AMA negativity and consistently normal ALP levels, illustrates how expanded laboratory testing can support the identification of non-standard disease phenotypes. In this setting, parallel testing for AMA- and PBC-specific autoantibodies was essential to achieve a correct diagnosis. Moreover, alternative biomarkers, including gamma-glutamyl transferase (GGT) and selected immunological markers, provided clinically meaningful information when conventional markers were not informative. CONCLUSIONS: By integrating current evidence with a long-term clinical case, this work moves beyond a descriptive overview and proposes a practical, laboratory-driven diagnostic and follow-up framework for PBC. It highlights laboratory opportunities to facilitate timely diagnosis, appropriate prognostic stratification, and disease monitoring, including the assessment of associated comorbidities.