Elisabeth M G de Vries1, Joanne Verheij2, Stefan G Hubscher3, Mariska M G Leeflang4, Kirsten Boonstra1, Ulrich Beuers1, Cyriel Y Ponsioen5. 1. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. 2. Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. 3. School of Cancer Sciences, University of Birmingham and Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, United Kingdom. 4. Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands. 5. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: c.y.ponsioen@amc.uva.nl.
Abstract
BACKGROUND & AIMS: 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. CONCLUSION: 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.
BACKGROUND & AIMS: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. CONCLUSION: 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: Christopher L Welle; Patrick J Navin; Michael C Olson; Safa Hoodeshenas; Michael S Torbenson; Sudhakar K Venkatesh Journal: Abdom Radiol (NY) Date: 2022-05-14
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
Authors: Michael Trauner; Yevgeniy Gindin; Zhaoshi Jiang; Chuhan Chung; G Mani Subramanian; Robert P Myers; Aliya Gulamhusein; Kris V Kowdley; Cynthia Levy; Zachary Goodman; Michael P Manns; Andrew J Muir; Christopher L Bowlus Journal: JHEP Rep Date: 2019-12-05
Authors: Nora Cazzagon; Samantha Sarcognato; Annarosa Floreani; Giorgia Corrà; Sara De Martin; Vincenza Guzzardo; Francesco Paolo Russo; Maria Guido Journal: JHEP Rep Date: 2021-03-30