A Dual Time Window-driven Strategy to Optimize Primary Biliary Cholangitis Treatment via Alkaline Phosphatase...

Area of Science:

• Hepatology
• Biochemistry
• Clinical Medicine

Background:

• Current primary biliary cholangitis (PBC) treatment targets alkaline phosphatase (ALP) ≤1.67 × upper limit of normal (ULN) at 12 months.
• A subset of patients meeting this criterion still progress to liver decompensation.
• Optimizing PBC management requires refining treatment targets and risk stratification.

Purpose of the Study:

• Establish ALP normalization as a core treatment target in PBC.
• Identify early intervention windows for optimizing patient outcomes.
• Develop robust risk stratification criteria for PBC patients.

Main Methods:

• Multicenter retrospective study with internal and external validation cohorts.
• Kaplan-Meier and Cox regression analyzed the prognostic impact of ALP normalization.
• Sankey diagrams and segmented Poisson regression identified risk transition points and intervention windows.

Main Results:

• Patients achieving ALP normalization had significantly higher complication-free survival (89.8% vs. 79.8%).
• Critical intervention windows identified at 3.73 months (high-to-medium risk) and 5.5 months (medium-to-low risk).
• Toronto criteria at 3 months showed 95% NPV for predicting non-normalization; Paris II criteria at 6 months offered 73% specificity.

Conclusions:

• ALP normalization is a significant predictor of improved clinical outcomes in PBC.
• Early intervention is warranted for patients with ALP ≥ 1.67 × ULN at 3 months.
• Patients not meeting Paris II criteria by 6 months require closer monitoring and potential intervention.