Primary biliary cholangitis: Beyond classical histopathology - diagnostic challenges in native and transplanted...

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterised by immune-mediated injury of small intrahepatic bile ducts, ultimately leading to progressive fibrosis, cirrhosis, and liver-related complications. Although diagnosis is typically established through cholestatic biochemical abnormalities and positivity of anti-mitochondrial antibodies, liver biopsy remains an important diagnostic tool in selected clinical settings, including atypical presentations, suspected overlap syndromes, and assessment of post-transplant liver dysfunction. Traditionally, the histopathology of PBC has been defined by chronic non-suppurative destructive cholangitis, progressive ductopenia, and biliary fibrosis. However, PBC encompasses a broader histopathological spectrum than traditionally recognised. In addition to classical lesions, contemporary liver biopsies may demonstrate distinct phenotypic patterns, including non-destructive ductopenia, inflammatory overlap-like changes, porto-sinusoidal vascular disease-associated lesions, and therapy-modified morphology. Recognition of these manifestations is important for accurate diagnosis, prognostic assessment, and avoidance of common diagnostic pitfalls. This review summarises the expanding histopathological spectrum of PBC in native and transplanted livers, with emphasis on emerging morphological phenotypes, treatment-related changes, recurrent disease after liver transplantation, and contemporary differential diagnostic challenges.