Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease

Elena Buzzetti, Andrew Hall, Mattias Ekstedt, Roberta Manuguerra, Marta Guerrero Misas, Claudia Covelli, Gioacchino Leandro, TuVinh Luong, Stergios Kechagias, Emanuel K Manesis, Massimo Pinzani, Amar P Dhillon, Emmanuel A Tsochatzis

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis.

AIM: To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD.

METHODS: We assessed consecutive patients with biopsy-proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow-up or death. CPA was performed at two different objective magnifications, whole biopsy macro and ×4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub-group of patients.

RESULTS: Of 437 patients, 32 (7.3%) decompensated and/or died from liver-related causes during a median follow-up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0-F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01-1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01-1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02-47.84) were independent predictors of liver-related clinical outcomes at standard and competing risk multivariate Cox-regression analysis.

CONCLUSIONS: CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials.

Original languageEnglish
Pages (from-to)1214-1222
Number of pages9
JournalAlimentary Pharmacology and Therapeutics
Volume49
Issue number9
DOIs
Publication statusPublished - May 2019

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Collagen
Fibrosis
Liver
Biopsy
Non-alcoholic Fatty Liver Disease
Liver Cirrhosis
Biomarkers
Regression Analysis
Clinical Trials

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Buzzetti, E., Hall, A., Ekstedt, M., Manuguerra, R., Guerrero Misas, M., Covelli, C., ... Tsochatzis, E. A. (2019). Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease. Alimentary Pharmacology and Therapeutics, 49(9), 1214-1222. https://doi.org/10.1111/apt.15219

Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease. / Buzzetti, Elena; Hall, Andrew; Ekstedt, Mattias; Manuguerra, Roberta; Guerrero Misas, Marta; Covelli, Claudia; Leandro, Gioacchino; Luong, TuVinh; Kechagias, Stergios; Manesis, Emanuel K; Pinzani, Massimo; Dhillon, Amar P; Tsochatzis, Emmanuel A.

In: Alimentary Pharmacology and Therapeutics, Vol. 49, No. 9, 05.2019, p. 1214-1222.

Research output: Contribution to journalArticle

Buzzetti, E, Hall, A, Ekstedt, M, Manuguerra, R, Guerrero Misas, M, Covelli, C, Leandro, G, Luong, T, Kechagias, S, Manesis, EK, Pinzani, M, Dhillon, AP & Tsochatzis, EA 2019, 'Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease', Alimentary Pharmacology and Therapeutics, vol. 49, no. 9, pp. 1214-1222. https://doi.org/10.1111/apt.15219
Buzzetti, Elena ; Hall, Andrew ; Ekstedt, Mattias ; Manuguerra, Roberta ; Guerrero Misas, Marta ; Covelli, Claudia ; Leandro, Gioacchino ; Luong, TuVinh ; Kechagias, Stergios ; Manesis, Emanuel K ; Pinzani, Massimo ; Dhillon, Amar P ; Tsochatzis, Emmanuel A. / Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease. In: Alimentary Pharmacology and Therapeutics. 2019 ; Vol. 49, No. 9. pp. 1214-1222.
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title = "Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease",
abstract = "BACKGROUND: Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis.AIM: To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD.METHODS: We assessed consecutive patients with biopsy-proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow-up or death. CPA was performed at two different objective magnifications, whole biopsy macro and ×4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub-group of patients.RESULTS: Of 437 patients, 32 (7.3{\%}) decompensated and/or died from liver-related causes during a median follow-up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0-F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95{\%} CI: 1.01-1.08), HM CPA (HR: 1.04 per 1{\%} increase, 95{\%} CI: 1.01-1.08) and presence of advanced fibrosis (HR: 15.4, 95{\%} CI: 5.02-47.84) were independent predictors of liver-related clinical outcomes at standard and competing risk multivariate Cox-regression analysis.CONCLUSIONS: CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials.",
author = "Elena Buzzetti and Andrew Hall and Mattias Ekstedt and Roberta Manuguerra and {Guerrero Misas}, Marta and Claudia Covelli and Gioacchino Leandro and TuVinh Luong and Stergios Kechagias and Manesis, {Emanuel K} and Massimo Pinzani and Dhillon, {Amar P} and Tsochatzis, {Emmanuel A}",
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TY - JOUR

T1 - Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease

AU - Buzzetti, Elena

AU - Hall, Andrew

AU - Ekstedt, Mattias

AU - Manuguerra, Roberta

AU - Guerrero Misas, Marta

AU - Covelli, Claudia

AU - Leandro, Gioacchino

AU - Luong, TuVinh

AU - Kechagias, Stergios

AU - Manesis, Emanuel K

AU - Pinzani, Massimo

AU - Dhillon, Amar P

AU - Tsochatzis, Emmanuel A

N1 - © 2019 John Wiley & Sons Ltd.

PY - 2019/5

Y1 - 2019/5

N2 - BACKGROUND: Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis.AIM: To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD.METHODS: We assessed consecutive patients with biopsy-proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow-up or death. CPA was performed at two different objective magnifications, whole biopsy macro and ×4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub-group of patients.RESULTS: Of 437 patients, 32 (7.3%) decompensated and/or died from liver-related causes during a median follow-up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0-F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01-1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01-1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02-47.84) were independent predictors of liver-related clinical outcomes at standard and competing risk multivariate Cox-regression analysis.CONCLUSIONS: CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials.

AB - BACKGROUND: Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis.AIM: To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD.METHODS: We assessed consecutive patients with biopsy-proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow-up or death. CPA was performed at two different objective magnifications, whole biopsy macro and ×4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub-group of patients.RESULTS: Of 437 patients, 32 (7.3%) decompensated and/or died from liver-related causes during a median follow-up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0-F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01-1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01-1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02-47.84) were independent predictors of liver-related clinical outcomes at standard and competing risk multivariate Cox-regression analysis.CONCLUSIONS: CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials.

U2 - 10.1111/apt.15219

DO - 10.1111/apt.15219

M3 - Article

C2 - 30882933

VL - 49

SP - 1214

EP - 1222

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

SN - 0269-2813

IS - 9

ER -