Complication-Free Survival in a Real-World Cohort of PBC Patients: Deep Versus Adequate ALP Response to UDCA.

Challenge

Current PBC treatment guidelines define response to UDCA as adequate when ALP falls below 1.5–1.67x ULN, but emerging evidence suggested that ALP normalization—a 'deep' response—might confer additional survival benefit. This had not been validated in a large, real-world US cohort with long follow-up.

Solution

The TARGET-PBC longitudinal cohort was used to compare complication-free survival between patients achieving deep versus adequate ALP responses to UDCA, using Kaplan-Meier, Cox proportional hazards, and restricted mean survival time analyses with advanced fibrosis stratification.

Impact

Demonstrating that deep ALP response—and deep bilirubin response—are associated with significantly better complication-free survival, particularly in advanced fibrosis patients, provides the real-world foundation for guideline revision and supports the regulatory case for ALP normalization as a treatment target in PBC.