Reduction in alkaline phosphatase is associated with longer survival in primary sclerosing cholangitis, independent of dominant stenosis

Summary Background Alkaline phosphatase ( ALP ) is an important serum marker in primary sclerosing cholangitis ( PSC ). Patients with obstruction of the large bile ducts due to dominant strictures ( DS ) are a special, clinically important phenotype. Aim To determine the impact of ALP reduction on liver transplantation‐free survival in PSC patients with DS . Methods Prospective cohort study in 215 PSC patients. We performed subgroup analysis for patients without DS (no DS , n  = 84), DS at first presentation ( DS early, n  = 72) and development of DS during the course of the study ( DS late, n  = 59). We evaluated two scores of ALP reduction. ALP reduction 1 was defined as ALP normalisation, 50% reduction compared with baseline values, or reduction below 1.5 times of upper limit of normal ( ULN ) within 6 months. ALP reduction 2 was defined as ALP reduction below 1.5 times of ULN within 12 months. Results Of the patients, 59.5% reached an ALP reduction 1 and 56.7% according to ALP reduction 2. Achievement of each score was associated with longer transplantation‐free survival in all three groups ( ALP reduction 1: no DS P  = 0.001; DS early P  < 0.001; DS late P  = 0.022; ALP reduction 2: no DS P  = 0.014; DS early P  = 0.001; DS late P  = 0.002). Cox‐regression analysis revealed each score as an independent predictor for improved transplantation‐free survival ( ALP reduction 1 and 2 P  < 0.001 each). We further analysed previously published scores of ALP improvement in PSC showing also improved survival in patients with ALP normalisation or a reduction below 1.5 times of ULN ( P  = 0.003, P  = 0.001, respectively), whereas the score determined by 40% reduction did not show significant differences in survival ( P  = 0.55). Conclusions Reduction in alkaline phosphatase values within the first year is associated with improved transplantation‐free survival in patients with primary sclerosing cholangitis independent of the presence of dominant strictures . Alkaline phosphatase might be an adequate surrogate marker for outcome assessment in clinical studies both for patients with and without dominant strictures .