Moira Hilscher1, Felicity B Enders2, Elizabeth J Carey3, Keith D Lindor4, James H Tabibian5. 1. Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA. 2. Division of Biomedical Statistics & Informatics, Mayo Clinic, Rochester, MN, USA. 3. Division of Gastroenterology & Hepatology, Mayo Clinic, Scottsdale, AZ, USA. 4. Executive Vice Provost & Dean, College of Health Solutions, Arizona State University, Phoenix, AZ, USA; Division of Gastroenterology & Hepatology. Mayo Clinic, Scottsdale, AZ. 5. Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA.
Abstract
UNLABELLED: Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis. MATERIAL AND METHODS: This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint-free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses. RESULTS: Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint-free survival. CONCLUSIONS: Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis.
UNLABELLED: Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis. MATERIAL AND METHODS: This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint-free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses. RESULTS: Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint-free survival. CONCLUSIONS: Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis.
Authors: Zeinab Bakhshi; Moira B Hilscher; Gregory J Gores; William S Harmsen; Jason K Viehman; Nicholas F LaRusso; Andrea A Gossard; Konstantinos N Lazaridis; Keith D Lindor; John E Eaton Journal: J Gastroenterol Date: 2020-01-13 Impact factor: 7.527
Authors: John E Eaton; Mette Vesterhus; Bryan M McCauley; Elizabeth J Atkinson; Erik M Schlicht; Brian D Juran; Andrea A Gossard; Nicholas F LaRusso; Gregory J Gores; Tom H Karlsen; Konstantinos N Lazaridis Journal: Hepatology Date: 2018-12-28 Impact factor: 17.425
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