Clinicopathological features of hepatobiliary cells in primary biliary cholangitis patients with incomplete response to ursodeoxycholic acid

BACKGROUND: The underlying mechanisms of incomplete response to ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cholangitis (PBC) remain unclear. This study aimed to investigate the clinicopathological characteristics and potential mechanisms of hepatobiliary (HB) cells in PBC patients with an incomplete response to UDCA. METHODS: A total of 132 PBC patients who underwent ultrasound-guided liver biopsy were enrolled. Liver tissue samples were processed using multiple histochemical staining methods. Demographic, clinical, hematological, autoantibody, and biochemical data were retrospectively analyzed. The therapeutic response to UDCA was evaluated according to the Paris II criteria. Additionally, bile acid metabolomic profiling was performed using liquid chromatography-mass spectrometry (LC-MS) on paraffin-embedded liver tissues from 25 randomly selected PBC patients. RESULTS: Among the 132 patients, 58 (43.9%) exhibited an incomplete response to UDCA. The number of CK7⁺ HB cells, degree of hepatocellular copper deposition, levels of alkaline phosphatase (ALP), total bile acid (TBA), and anti-GP210 antibody were significantly associated with incomplete response to UDCA. These factors exhibited AUC values of 0.745, 0.678, 0.809, 0.770 and 0.588, respectively. Hepatic levels of TBA (p = 0.010) and glycoursodeoxycholic acid (GUDCA, p = 0.037) were significantly higher in the incomplete response group compared with the complete response group. Moreover, the abundance of CK7⁺ HB cells was positively correlated with hepatic TBA (r = 0.544, p < 0.01) and GUDCA (r = 0.480, p < 0.05) levels. CONCLUSIONS: PBC patients with an incomplete response to UDCA exhibited a significant increase in CK7⁺ HB cells, which were independently associated with treatment incomplete response. Although biochemical parameters such as ALP and TBA remain key predictors of incomplete response to UDCA, CK7⁺ HB cells provide additional histological insights into the mechanisms underlying incomplete therapeutic response.