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

Francesca Saffioti, Andrew Hall, Manon de Krijger, Joanne Verheij, Stefan G Hübscher, James Maurice, Tu Vinh Luong, Massimo Pinzani, Cyriel Y Ponsioen, Douglas Thorburn

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2681-2692
Number of pages12
JournalLiver international
Volume41
Issue number11
Early online date2021
DOIs
Publication statusPublished - Nov 2021

Keywords

  • Cholangitis, Sclerosing/pathology
  • Collagen
  • Humans
  • Liver Cirrhosis/pathology
  • Liver/pathology
  • Prospective Studies
  • Retrospective Studies

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