title: Applicability and prognostic value of histologic scoring systems in primary sclerosing cholangitis.
abstract: OBJECTIVE
  Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. At present, there is no appropriate histologic scoring system available for PSC, evaluating both degree of necroinflammatory activity (grade) and fibrosis (stage). The aim of this study was to assess if three scoring systems, commonly used in different liver diseases could be applied for grading and/or staging of PSC.
  
  
  METHODS
  Sixty-four PSC patients from a Dutch cohort, who underwent diagnostic liver biopsy, were included. Staging was scored using Ishak, Nakanuma, and Ludwig systems. Grading was scored using Ishak and Nakanuma systems. Three measures of outcome were defined; transplant-free survival, time to liver transplantation (LTx) and occurrence of cirrhosis related symptoms (CRS). Association of grade and stage with outcome was estimated using Kaplan-Meier log-rank test, and Cox regression analysis. Correlation with biochemistry was assessed by Spearman's rank test.
  
  
  RESULTS
  There were strong associations between disease stage measured by Ishak, Nakanuma, and Ludwig staging systems with both outcome measuring transplant-free survival (Hazard ratio (HR) 2.56; 95% CI 1.11-5.89, HR 6.53; 95% CI 2.01-21.22, HR 1.94; 95% CI 1.00-3.79, respectively), and time to LTx (HR 4.18; 95%CI 1.51-11.56, HR 7.05; 95% CI 1.77-28.11, HR 3.13; 95%CI 1.42-6.87, respectively). Ishak and Nakanuma grading systems were not associated with CRS. Weak correlations between histopathology and liver biochemistry were shown.
  
  
  CONCLUSIONS
  Applying the Nakanuma, Ishak, and Ludwig histopathological staging systems is feasible and clinically relevant given their association with transplant-free survival and time to LTx. This suggests that these staging systems could be likely candidates for surrogate endpoints and stratification purposes in clinical trials in PSC.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Elisabeth M G
authors.initials: EM
authors.lastname: de Vries
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Joanne
authors.initials: J
authors.lastname: Verheij
authors.affiliation: School of Cancer Sciences, University of Birmingham and Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Hubscher
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Mariska M G
authors.initials: MM
authors.lastname: Leeflang
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Boonstra
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: c.y.ponsioen@amc.uva.nl.
authors.forename: Cyriel Y
authors.initials: CY
authors.lastname: Ponsioen
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015209:Cholangitis, Sclerosing / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
chemical_list: D015415:Biomarkers
keywords: Histologic scoring system; Histology; Primary sclerosing cholangitis; Prognosis; Surrogate endpoint