Reduction of alkaline phosphatase levels improves survival in PSC patients independent of dominant stenosis

Background & Aims: Alkaline phosphatase (AP) is an important serum marker in primary sclerosing cholangitis (PSC). Patients with biliary obstructions of the large bile ducts due to dominant strictures resemble a special, clinically important phenotype. We aimed to assess the value of AP in predicting outcome depending on the presence of dominant strictures.

Patients and methods: This is a prospective cohort study of 218 PSC patients that were treated with UDCA and endoscopic interventions over the period 1987 – 2012 in our tertiary care center. Laboratory values were examined in at least yearly intervals.

Results: The median AP level at inclusion into the study was 287.2 ± 24.7 IU/l. Patients with dominant stenosis (DS) showed higher AP levels at first presentation (422.6 IU/l vs. 315.3 IU/l). 108 patients (49.5%) reached a sustained AP reduction below 1.5 x ULN between six and twelve month after inclusion into the study. The proportion of successful AP reduction did not differ between patients with or without DS (50.8% vs. 49.3%). We performed further subgroup analysis for patients without DS (group A, n = 95), DS at first presentation (group B, n = 58) and development of DS during the course of the study (group C, n = 65). Reduction of AP below 1.5 x ULN within six to twelve month was associated with better outcome in group A (log rank: p = 0.03), group B (log rank: p = 0.04) and group C (log rank: p = 0.005). Evaluation of reduction of bilirubin and gamma-glutamyltransferase levels showed no impact on survival. Failed reduction of none of the three serum markers was associated with development of DS. Cox-regression analysis including AP reduction, presence of DS, presence of IBD and Mayo-Risk-Score at baseline revealed only AP reduction as the only independent predictor for improved survival (p = 0.008).

Conclusion: Sustained AP reduction below 1.5 x ULN within the first year is associated with improved transplantation-free survival in patients independent of the presence of biliary obstruction due to dominant strictures. AP might be an adequate surrogate marker for outcome assessment in clinical studies for patients with and as well for patients without dominant strictures.