Validation of the prognostic value of histologic scoring systems in primary sclerosing cholangitis: An international cohort study

Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic use and reproducibility a...

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Vydané v:	Hepatology (Baltimore, Md.) Ročník 65; číslo 3; s. 907 - 919
Hlavní autori:	de Vries, Elisabeth M. G., de Krijger, Manon, Färkkilä, Martti, Arola, Johanna, Schirmacher, Peter, Gotthardt, Daniel, Goeppert, Benjamin, Trivedi, Palak J., Hirschfield, Gideon M., Ytting, Henriette, Vainer, Ben, Buuren, Henk R. van, Biermann, Katharina, Harms, Maren H., Chazouilleres, Olivier, Wendum, Dominique, Kemgang, Astrid D., Chapman, Roger W., Wang, Lai Mun, Williamson, Kate D., Gouw, Annette S. H., Paradis, Valerie, Sempoux, Christine, Beuers, Ulrich, Hübscher, Stefan G., Verheij, Joanne, Ponsioen, Cyriel Y.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Wolters Kluwer Health, Inc 01.03.2017 Wiley-Blackwell
Predmet:	Adult Biopsy Biopsy, Needle Cholangitis, Sclerosing - mortality Cholangitis, Sclerosing - pathology Cholangitis, Sclerosing - surgery Cohort Studies Female Hepatology Humans Immunohistochemistry Internationality Kaplan-Meier Estimate Life Sciences Liver Liver Transplantation - methods Liver Transplantation - mortality Male Middle Aged Multivariate Analysis Observer Variation Prognosis Proportional Hazards Models Risk Assessment Severity of Illness Index Survival Rate Treatment Outcome
ISSN:	0270-9139, 1527-3350
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Abstract	Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic use and reproducibility across a multicenter PSC cohort. Liver biopsies from PSC patients were collected from seven European institutions. Histologic scoring was performed using the Nakanuma, Ishak, and Ludwig scoring systems. Biopsies were independently scored by six liver pathologists for interobserver agreement. The prognostic value of clinical, biochemical, and all three histologic scoring systems on predicting composite endpoints 1 (PSC‐related death and liver transplantation), 2 (liver transplantation), and 3 (liver‐related events), was assessed using univariable and multivariable Cox proportional hazards modeling. A total of 119 PSC patients were identified, and the median follow‐up was 142 months. During follow‐up, 31 patients died (20 PSC‐related deaths), 31 patients underwent liver transplantation, and 35 patients experienced one or more liver‐related events. All three staging systems were independent predictors of endpoints 2 and 3 (Nakanuma system: hazard ratio [HR], 3.16 [95% confidence interval (CI), 1.49‐6.68] for endpoint 2 and HR, 2.05 [95% CI, 1.17‐3.57] for endpoint 3; Ishak system: HR, 1.55 [95% CI, 1.10‐2.18] for endpoint 2 and HR, 1.43 [95% CI, 1.10‐1.85] for endpoint 3; Ludwig system: HR, 2.62 [95% CI, 1.19‐5.80] for endpoint 2 and HR, 2.06 [95% CI, 1.09‐3.89] for endpoint 3). Only the Nakanuma staging system was independently associated with endpoint 1: HR, 2.14 (95% CI, 1.22‐3.77). Interobserver agreement was moderate for Nakanuma stage (κ = 0.56) and substantial for Nakanuma component fibrosis (κ = 0.67), Ishak stage (κ = 0.64), and Ludwig stage (κ = 0.62). Conclusion: We confirm the independent prognostic value and demonstrate for the first time the reproducibility of staging disease progression in PSC using the Nakanuma, Ishak, and Ludwig staging systems. The Nakanuma staging system—incorporating features of chronic biliary disease—again showed the strongest predictive value. (Hepatology 2017;65:907‐919).
AbstractList	Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic use and reproducibility across a multicenter PSC cohort. Liver biopsies from PSC patients were collected from seven European institutions. Histologic scoring was performed using the Nakanuma, Ishak, and Ludwig scoring systems. Biopsies were independently scored by six liver pathologists for interobserver agreement. The prognostic value of clinical, biochemical, and all three histologic scoring systems on predicting composite endpoints 1 (PSC-related death and liver transplantation), 2 (liver transplantation), and 3 (liver-related events), was assessed using univariable and multivariable Cox proportional hazards modeling. A total of 119 PSC patients were identified, and the median follow-up was 142 months. During follow-up, 31 patients died (20 PSC-related deaths), 31 patients underwent liver transplantation, and 35 patients experienced one or more liver-related events. All three staging systems were independent predictors of endpoints 2 and 3 (Nakanuma system: hazard ratio [HR], 3.16 [95% confidence interval (CI), 1.49-6.68] for endpoint 2 and HR, 2.05 [95% CI, 1.17-3.57] for endpoint 3; Ishak system: HR, 1.55 [95% CI, 1.10-2.18] for endpoint 2 and HR, 1.43 [95% CI, 1.10-1.85] for endpoint 3; Ludwig system: HR, 2.62 [95% CI, 1.19-5.80] for endpoint 2 and HR, 2.06 [95% CI, 1.09-3.89] for endpoint 3). Only the Nakanuma staging system was independently associated with endpoint 1: HR, 2.14 (95% CI, 1.22-3.77). Interobserver agreement was moderate for Nakanuma stage (κ = 0.56) and substantial for Nakanuma component fibrosis (κ = 0.67), Ishak stage (κ = 0.64), and Ludwig stage (κ = 0.62).CONCLUSIONWe confirm the independent prognostic value and demonstrate for the first time the reproducibility of staging disease progression in PSC using the Nakanuma, Ishak, and Ludwig staging systems. The Nakanuma staging system-incorporating features of chronic biliary disease-again showed the strongest predictive value. (Hepatology 2017;65:907-919). Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic use and reproducibility across a multicenter PSC cohort. Liver biopsies from PSC patients were collected from seven European institutions. Histologic scoring was performed using the Nakanuma, Ishak, and Ludwig scoring systems. Biopsies were independently scored by six liver pathologists for interobserver agreement. The prognostic value of clinical, biochemical, and all three histologic scoring systems on predicting composite endpoints 1 (PSC-related death and liver transplantation), 2 (liver transplantation), and 3 (liver-related events), was assessed using univariable and multivariable Cox proportional hazards modeling. A total of 119 PSC patients were identified, and the median follow-up was 142 months. During follow-up, 31 patients died (20 PSC-related deaths), 31 patients underwent liver transplantation, and 35 patients experienced one or more liver-related events. All three staging systems were independent predictors of endpoints 2 and 3 (Nakanuma system: hazard ratio [HR], 3.16 [95% confidence interval (CI), 1.49-6.68] for endpoint 2 and HR, 2.05 [95% CI, 1.17-3.57] for endpoint 3; Ishak system: HR, 1.55 [95% CI, 1.10-2.18] for endpoint 2 and HR, 1.43 [95% CI, 1.10-1.85] for endpoint 3; Ludwig system: HR, 2.62 [95% CI, 1.19-5.80] for endpoint 2 and HR, 2.06 [95% CI, 1.09-3.89] for endpoint 3). Only the Nakanuma staging system was independently associated with endpoint 1: HR, 2.14 (95% CI, 1.22-3.77). Interobserver agreement was moderate for Nakanuma stage ([kappa] = 0.56) and substantial for Nakanuma component fibrosis ([kappa] = 0.67), Ishak stage ([kappa] = 0.64), and Ludwig stage ([kappa] = 0.62). Conclusion: We confirm the independent prognostic value and demonstrate for the first time the reproducibility of staging disease progression in PSC using the Nakanuma, Ishak, and Ludwig staging systems. The Nakanuma staging system--incorporating features of chronic biliary disease--again showed the strongest predictive value. (Hepatology 2017;65:907-919). Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic use and reproducibility across a multicenter PSC cohort. Liver biopsies from PSC patients were collected from seven European institutions. Histologic scoring was performed using the Nakanuma, Ishak, and Ludwig scoring systems. Biopsies were independently scored by six liver pathologists for interobserver agreement. The prognostic value of clinical, biochemical, and all three histologic scoring systems on predicting composite endpoints 1 (PSC-related death and liver transplantation), 2 (liver transplantation), and 3 (liver-related events), was assessed using univariable and multivariable Cox proportional hazards modeling. A total of 119 PSC patients were identified, and the median follow-up was 142 months. During follow-up, 31 patients died (20 PSC-related deaths), 31 patients underwent liver transplantation, and 35 patients experienced one or more liver-related events. All three staging systems were independent predictors of endpoints 2 and 3 (Nakanuma system: hazard ratio [HR], 3.16 [95% confidence interval (CI), 1.49-6.68] for endpoint 2 and HR, 2.05 [95% CI, 1.17-3.57] for endpoint 3; Ishak system: HR, 1.55 [95% CI, 1.10-2.18] for endpoint 2 and HR, 1.43 [95% CI, 1.10-1.85] for endpoint 3; Ludwig system: HR, 2.62 [95% CI, 1.19-5.80] for endpoint 2 and HR, 2.06 [95% CI, 1.09-3.89] for endpoint 3). Only the Nakanuma staging system was independently associated with endpoint 1: HR, 2.14 (95% CI, 1.22-3.77). Interobserver agreement was moderate for Nakanuma stage (κ = 0.56) and substantial for Nakanuma component fibrosis (κ = 0.67), Ishak stage (κ = 0.64), and Ludwig stage (κ = 0.62). We confirm the independent prognostic value and demonstrate for the first time the reproducibility of staging disease progression in PSC using the Nakanuma, Ishak, and Ludwig staging systems. The Nakanuma staging system-incorporating features of chronic biliary disease-again showed the strongest predictive value. (Hepatology 2017;65:907-919). Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic use and reproducibility across a multicenter PSC cohort. Liver biopsies from PSC patients were collected from seven European institutions. Histologic scoring was performed using the Nakanuma, Ishak, and Ludwig scoring systems. Biopsies were independently scored by six liver pathologists for interobserver agreement. The prognostic value of clinical, biochemical, and all three histologic scoring systems on predicting composite endpoints 1 (PSC‐related death and liver transplantation), 2 (liver transplantation), and 3 (liver‐related events), was assessed using univariable and multivariable Cox proportional hazards modeling. A total of 119 PSC patients were identified, and the median follow‐up was 142 months. During follow‐up, 31 patients died (20 PSC‐related deaths), 31 patients underwent liver transplantation, and 35 patients experienced one or more liver‐related events. All three staging systems were independent predictors of endpoints 2 and 3 (Nakanuma system: hazard ratio [HR], 3.16 [95% confidence interval (CI), 1.49‐6.68] for endpoint 2 and HR, 2.05 [95% CI, 1.17‐3.57] for endpoint 3; Ishak system: HR, 1.55 [95% CI, 1.10‐2.18] for endpoint 2 and HR, 1.43 [95% CI, 1.10‐1.85] for endpoint 3; Ludwig system: HR, 2.62 [95% CI, 1.19‐5.80] for endpoint 2 and HR, 2.06 [95% CI, 1.09‐3.89] for endpoint 3). Only the Nakanuma staging system was independently associated with endpoint 1: HR, 2.14 (95% CI, 1.22‐3.77). Interobserver agreement was moderate for Nakanuma stage (κ = 0.56) and substantial for Nakanuma component fibrosis (κ = 0.67), Ishak stage (κ = 0.64), and Ludwig stage (κ = 0.62). Conclusion: We confirm the independent prognostic value and demonstrate for the first time the reproducibility of staging disease progression in PSC using the Nakanuma, Ishak, and Ludwig staging systems. The Nakanuma staging system—incorporating features of chronic biliary disease—again showed the strongest predictive value. (Hepatology 2017;65:907‐919). Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic use and reproducibility across a multicenter PSC cohort. Liver biopsies from PSC patients were collected from seven European institutions. Histologic scoring was performed using the Nakanuma, Ishak, and Ludwig scoring systems. Biopsies were independently scored by six liver pathologists for interobserver agreement. The prognostic value of clinical, biochemical, and all three histologic scoring systems on predicting composite endpoints 1 (PSC‐related death and liver transplantation), 2 (liver transplantation), and 3 (liver‐related events), was assessed using univariable and multivariable Cox proportional hazards modeling. A total of 119 PSC patients were identified, and the median follow‐up was 142 months. During follow‐up, 31 patients died (20 PSC‐related deaths), 31 patients underwent liver transplantation, and 35 patients experienced one or more liver‐related events. All three staging systems were independent predictors of endpoints 2 and 3 (Nakanuma system: hazard ratio [HR], 3.16 [95% confidence interval (CI), 1.49‐6.68] for endpoint 2 and HR, 2.05 [95% CI, 1.17‐3.57] for endpoint 3; Ishak system: HR, 1.55 [95% CI, 1.10‐2.18] for endpoint 2 and HR, 1.43 [95% CI, 1.10‐1.85] for endpoint 3; Ludwig system: HR, 2.62 [95% CI, 1.19‐5.80] for endpoint 2 and HR, 2.06 [95% CI, 1.09‐3.89] for endpoint 3). Only the Nakanuma staging system was independently associated with endpoint 1: HR, 2.14 (95% CI, 1.22‐3.77). Interobserver agreement was moderate for Nakanuma stage (κ = 0.56) and substantial for Nakanuma component fibrosis (κ = 0.67), Ishak stage (κ = 0.64), and Ludwig stage (κ = 0.62). Conclusion : We confirm the independent prognostic value and demonstrate for the first time the reproducibility of staging disease progression in PSC using the Nakanuma, Ishak, and Ludwig staging systems. The Nakanuma staging system—incorporating features of chronic biliary disease—again showed the strongest predictive value. (H epatology 2017;65:907‐919).
Author	Biermann, Katharina Wang, Lai Mun Hirschfield, Gideon M. Kemgang, Astrid D. Beuers, Ulrich Gouw, Annette S. H. Chapman, Roger W. de Vries, Elisabeth M. G. de Krijger, Manon Williamson, Kate D. Trivedi, Palak J. Ytting, Henriette Chazouilleres, Olivier Ponsioen, Cyriel Y. Goeppert, Benjamin Sempoux, Christine Verheij, Joanne Vainer, Ben Färkkilä, Martti Paradis, Valerie Harms, Maren H. Wendum, Dominique Arola, Johanna Hübscher, Stefan G. Schirmacher, Peter Gotthardt, Daniel Buuren, Henk R. van
Author_xml	– sequence: 1 givenname: Elisabeth M. G. surname: de Vries fullname: de Vries, Elisabeth M. G. organization: Academic Medical Center – sequence: 2 givenname: Manon surname: de Krijger fullname: de Krijger, Manon organization: Academic Medical Center – sequence: 3 givenname: Martti surname: Färkkilä fullname: Färkkilä, Martti organization: Helsinki University and Helsinki University Hospital, Department of Gastroenterology – sequence: 4 givenname: Johanna surname: Arola fullname: Arola, Johanna organization: Helsinki University and Helsinki University Hospital – sequence: 5 givenname: Peter surname: Schirmacher fullname: Schirmacher, Peter organization: University Hospital Heidelberg – sequence: 6 givenname: Daniel surname: Gotthardt fullname: Gotthardt, Daniel organization: University Hospital Heidelberg – sequence: 7 givenname: Benjamin surname: Goeppert fullname: Goeppert, Benjamin organization: University Hospital Heidelberg – sequence: 8 givenname: Palak J. surname: Trivedi fullname: Trivedi, Palak J. organization: National Institute for Health Research, Birmingham Liver Biomedical Research Unit, Institute of Immunology and Immunotherapy, University of Birmingham – sequence: 9 givenname: Gideon M. surname: Hirschfield fullname: Hirschfield, Gideon M. organization: National Institute for Health Research, Birmingham Liver Biomedical Research Unit, Institute of Immunology and Immunotherapy, University of Birmingham – sequence: 10 givenname: Henriette surname: Ytting fullname: Ytting, Henriette organization: Rigshospitalet, University of Copenhagen – sequence: 11 givenname: Ben surname: Vainer fullname: Vainer, Ben organization: Rigshospitalet, University of Copenhagen – sequence: 12 givenname: Henk R. van surname: Buuren fullname: Buuren, Henk R. van organization: Erasmus University Medical Center – sequence: 13 givenname: Katharina surname: Biermann fullname: Biermann, Katharina organization: Erasmus University Medical Center – sequence: 14 givenname: Maren H. surname: Harms fullname: Harms, Maren H. organization: Erasmus University Medical Center – sequence: 15 givenname: Olivier surname: Chazouilleres fullname: Chazouilleres, Olivier organization: AP‐HP, Hôpital Saint‐Antoine, Sorbonne Universités, University Pierre and Marie Curie – sequence: 16 givenname: Dominique surname: Wendum fullname: Wendum, Dominique organization: AP‐HP, Hôpital Saint‐Antoine, Sorbonne Universités, University Pierre and Marie Curie – sequence: 17 givenname: Astrid D. surname: Kemgang fullname: Kemgang, Astrid D. organization: AP‐HP, Hôpital Saint‐Antoine, Sorbonne Universités, University Pierre and Marie Curie – sequence: 18 givenname: Roger W. surname: Chapman fullname: Chapman, Roger W. organization: John Radcliffe Hospital, Oxford – sequence: 19 givenname: Lai Mun surname: Wang fullname: Wang, Lai Mun organization: Ludwig Institute for Cancer Research – sequence: 20 givenname: Kate D. surname: Williamson fullname: Williamson, Kate D. organization: John Radcliffe Hospital, Oxford – sequence: 21 givenname: Annette S. H. surname: Gouw fullname: Gouw, Annette S. H. organization: University Medical Center Groningen – sequence: 22 givenname: Valerie surname: Paradis fullname: Paradis, Valerie organization: Assistance Publique‐Hôpitaux de Paris – sequence: 23 givenname: Christine surname: Sempoux fullname: Sempoux, Christine organization: Centre Hospitalier Universitaire Vaudois – sequence: 24 givenname: Ulrich surname: Beuers fullname: Beuers, Ulrich organization: Academic Medical Center – sequence: 25 givenname: Stefan G. surname: Hübscher fullname: Hübscher, Stefan G. organization: Queen Elizabeth Hospital – sequence: 26 givenname: Joanne surname: Verheij fullname: Verheij, Joanne organization: Academic Medical Center – sequence: 27 givenname: Cyriel Y. surname: Ponsioen fullname: Ponsioen, Cyriel Y. email: c.y.ponsioen@amc.uva.nl organization: Academic Medical Center
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ContentType	Journal Article
Copyright	2016 by the American Association for the Study of Liver Diseases. 2017 by the American Association for the Study of Liver Diseases Distributed under a Creative Commons Attribution 4.0 International License
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Notes	This paper presents independent research; as such, the views expressed are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, or the Department of Health. Potential conflict of interest: Dr. Ponsioen advises and has received grants from Takeda and AbbVie. Correction added on February 7, 2017, after first online publication: new affiliations 13 and 14 were added and the rest renumbered, resulting in a change in affiliation number for authors Lai Mun Wang, Annette S.H. Gouw, Valerie Paradis, Christine Sempoux, Stefan J. Hübscher, and Joanne Verheij. P.J.T. received funding from a Wellcome Trust Clinical Research Fellowship. P.J.T. and G.M.H. are supported by the National Institute for Health Research Birmingham Liver Biomedical Research Unit. Shared senior authors. Contributed equally to this study. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3
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Snippet	Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value...
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SubjectTerms	Adult Biopsy Biopsy, Needle Cholangitis, Sclerosing - mortality Cholangitis, Sclerosing - pathology Cholangitis, Sclerosing - surgery Cohort Studies Female Hepatology Humans Immunohistochemistry Internationality Kaplan-Meier Estimate Life Sciences Liver Liver Transplantation - methods Liver Transplantation - mortality Male Middle Aged Multivariate Analysis Observer Variation Prognosis Proportional Hazards Models Risk Assessment Severity of Illness Index Survival Rate Treatment Outcome
Title	Validation of the prognostic value of histologic scoring systems in primary sclerosing cholangitis: An international cohort study
URI	https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fhep.28963 https://www.ncbi.nlm.nih.gov/pubmed/27880989 https://www.proquest.com/docview/1870273757 https://www.proquest.com/docview/1843965853 https://www.proquest.com/docview/1877834444 https://hal.sorbonne-universite.fr/hal-03972290
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