ORIGINAL ARTICLE

Collagen proportionate area correlates with histological stage and predicts clinical events in primary sclerosing cholangitis

Corresponding Author

Francesca Saffioti

[email protected]

orcid.org/0000-0001-7635-9931

Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

Correspondence

Francesca Saffioti, Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

Email: [email protected]

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Andrew Hall,

Andrew Hall

Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

Department of Cellular Pathology, Royal Free Hospital, London, UK

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Manon de Krijger,

Manon de Krijger

Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Joanne Verheij,

Joanne Verheij

Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Stefan G. Hübscher,

Stefan G. Hübscher

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK

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James Maurice,

James Maurice

Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

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Tu Vinh Luong,

Tu Vinh Luong

Department of Cellular Pathology, Royal Free Hospital, London, UK

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Massimo Pinzani,

Massimo Pinzani

Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

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Cyriel Y. Ponsioen,

Cyriel Y. Ponsioen

Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Douglas Thorburn,

Douglas Thorburn

Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

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Francesca Saffioti,

Corresponding Author

Francesca Saffioti

[email protected]

orcid.org/0000-0001-7635-9931

Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

Correspondence

Francesca Saffioti, Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

Email: [email protected]

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Andrew Hall,

Andrew Hall

Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

Department of Cellular Pathology, Royal Free Hospital, London, UK

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Manon de Krijger,

Manon de Krijger

Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Joanne Verheij,

Joanne Verheij

Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Stefan G. Hübscher,

Stefan G. Hübscher

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, UK

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James Maurice,

James Maurice

Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

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Tu Vinh Luong,

Tu Vinh Luong

Department of Cellular Pathology, Royal Free Hospital, London, UK

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Massimo Pinzani,

Massimo Pinzani

Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

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Cyriel Y. Ponsioen,

Cyriel Y. Ponsioen

Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Douglas Thorburn,

Douglas Thorburn

Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health, University College of London, London, UK

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First published: 29 May 2021

https://doi.org/10.1111/liv.14979

Citations: 4

Funding information

MdK was supported by a research grant from Takeda.

Handling Editor: Ana Lleo

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Abstract

Background & Aims

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease in need of accurate biomarkers for stratification and as surrogates for clinical endpoints in trials. Quantitative liver fibrosis assessment by collagen proportionate area (CPA) measurement has been demonstrated to correlate with clinical outcomes in chronic hepatitis C, alcohol-related and non-alcoholic fatty liver disease. We aimed to investigate the ability of CPA to quantify liver fibrosis and predict clinical events in PSC.

Methods

Biopsies from 101 PSC patients from two European centres were retrospectively assessed by two expert pathologists in tandem, using grading (Ishak and Nakanuma) and staging (Ishak, Nakanuma, Ludwig) systems recently validated to predict clinical events in PSC. CPA was determined by image analysis of picro-Sirius red-stained sections following a standard protocol. We assessed the correlations between CPA, staging and grading and their associations with three outcomes: (1) time to PSC-related death, liver transplant or primary liver cancer; (2) liver transplant-free survival; (3) occurrence of cirrhosis-related clinical manifestations.

Results

CPA correlated strongly with histological stage determined by each scoring system (P < .001) and was significantly associated with the three endpoints. Median time to endpoint-1, endpoint-2 and endpoint-3 was shorter in patients with higher CPA, on Kaplan-Meier analyses (P = .011, P = .034 and P = .001, respectively).

Conclusion

Quantitative fibrosis assessment by CPA has utility in PSC. It correlates with established histological staging systems and predicts clinical events. CPA may be a useful tool for staging fibrosis and for risk stratification in PSC and should be evaluated further within prospective clinical trials.

CONFLICT OF INTEREST

All the authors have no conflict of interest with respect to this work.

Open Research

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Supporting Information

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Volume41, Issue11

November 2021

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Collagen proportionate area correlates with histological stage and predicts clinical events in primary sclerosing cholangitis

Abstract

Background & Aims

Methods

Results

Conclusion

CONFLICT OF INTEREST

Open Research

DATA AVAILABILITY STATEMENT

Supporting Information

REFERENCES

Citing Literature

References

Information

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Collagen proportionate area correlates with histological stage and predicts clinical events in primary sclerosing cholangitis

Abstract

Background & Aims

Methods

Results

Conclusion

CONFLICT OF INTEREST

Open Research

DATA AVAILABILITY STATEMENT

Supporting Information

REFERENCES

Citing Literature

References

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