Sex disparities in primary biliary cholangitis: insights from a Japanese multicentre cohort

Abstract Primary biliary cholangitis (PBC) is an autoimmune-related cholestatic liver disease predominantly affecting women, yet sex-specific differences in progression remain unclear. Multicenter retrospective analysis of 289 Japanese PBC patients compared sex disparities in demographics, laboratory parameters, histopathology, and prognostic scores. Males tended to be older at diagnosis, although this difference did not reach statistical significance. At diagnosis, significant laboratory differences were observed in total bilirubin and γGT, both higher in males ( p < 0.05), consistent with a slightly higher ALBI score in males ( p = 0.046), suggesting worse liver functional reserve. Males also had worse outcomes according to UK‑PBC Risk Scores and GLOBE score ( p < 0.05). Histologically, at comparable bile duct loss, males tended to exhibit higher orcein‑positive granule deposition scores than females, suggesting chronic cholestasis resulting from bile duct loss tends to be more pronounced in males. Furthermore, positive correlations between fibrosis and bile duct loss, and between fibrosis and orcein‑positive granule deposition, were observed in females but not in males. Among mild‑fibrosis patients, males exhibited greater orcein-positive granule deposition. This study demonstrates sex differences in PBC progression and suggests that males may exhibit more pronounced chronic cholestatic changes, as reflected by greater orcein‑positive granule deposition, particularly in mild fibrosis.