Histological characteristics of primary biliary cholangitis in patients with incomplete responses to ursodeoxycholic acid.

BACKGROUND AND AIMS: Ursodeoxycholic acid (UDCA) is the standard first-line therapy for primary biliary cholangitis (PBC), yet approximately 30-40 % of patients exhibit incomplete biochemical responses. This study aimed to identify the histopathological features associated with incomplete UDCA response by comparing liver biopsy specimens from these patients with those from treatment-naïve individuals, using the Nakanuma classification.

METHODS

We analyzed liver biopsy samples from 33 UDCA-incomplete responders and 152 treatment-naïve patients with PBC. Histological staging and grading were performed using the Nakanuma classification, which evaluates fibrosis, bile duct loss, and orcein-positive granule deposition for staging. Chronic cholangitis activity (CA) and hepatitis activity (HA) were categorized using a four-point scale.

RESULTS

Patients with incomplete UDCA responses showed significantly higher scores for bile duct loss, orcein-positive granule deposition, and HA compared with treatment-naïve patients, regardless of fibrosis stage. Notably, 82 % of incomplete responders were classified as stage 4 (advanced disease) by the Nakanuma system, whereas classical systems such as Scheuer and Ludwig frequently underestimated disease severity. Approximately half of the incomplete responders lacked histologically detectable bile ducts (CA0), indicating extensive ductopenia.

CONCLUSIONS

Liver histology in patients with incomplete responses to UDCA is characterized predominantly by advanced disease features, including severe hepatitis, bile duct loss, and orcein-positive granule deposition, rather than by fibrosis alone. The Nakanuma classification offers a more accurate evaluation of disease severity compared to conventional classifications. These histological findings provide valuable insights for interpreting the outcomes of recent clinical trials of second-line therapies for PBC, particularly those targeting immune-mediated mechanisms.