Collagen proportionate area predicts clinical outcomes in patients with alcohol‐related liver disease

Author:

Israelsen Mads123ORCID,Guerrero Misas Marta1,Koutsoumourakis Anastasios1,Huang Yi4ORCID,Thiele Maja23ORCID,Hall Andrew5,Rasmussen Ditlev23,Covelli Claudia6,Buzzetti Elena1,Prat Laura Iogna1,Roccarina Davide1,Detlefsen Sönke37,Luong Tu Vinh5,Quaglia Alberto5,Krag Aleksander23ORCID,Jeffrey Gary4,Pinzani Massimo1,Tsochatzis Emmanuel A.1ORCID

Affiliation:

1. UCL Institute for Liver and Digestive Health Royal Free Hospital and UCL London UK

2. Department of Gastroenterology and Hepatology Odense University Hospital Odense Denmark

3. Department of Clinical Research Faculty of Health Sciences University of Southern Denmark Odense Denmark

4. School of Medicine and Pharmacology University of Western Australia and Sir Charles Gairdner Hospital Perth WA Australia

5. Department of Cellular Pathology Royal Free London NHS Foundation Trust and UCL Institute for Liver and Digestive Health University College of London London UK

6. Pathology Unit Fondazione IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo (FG) Italy

7. Department of Pathology Odense University Hospital Odense Denmark

Abstract

SummaryBackgroundNo prognostic tools are established for alcohol‐related liver disease (ALD). Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies using digital image analysis.AimTo assess the predictive value of CPA on hepatic decompensation and liver‐related mortality in ALDMethodsIn a multicentre cohort study, we included 386 patients with biopsy‐verified ALD and with long‐term follow‐up. In the development cohort of 276 patients, we assessed the predictors of hepatic decompensation and liver‐related death in standard and competing risk multivariable Cox regression analyses. The results were validated in an independent prospective cohort of 110 patients, where CPA was also correlated with liver stiffness measurement (LSM).ResultsIn the development cohort, 231 (84%) patients had early/compensated ALD (non‐cirrhotic or compensated cirrhosis) and 45 (16%) had decompensated cirrhosis. In the validation cohort, all patients had early/compensated ALD. Independent predictors of liver‐related mortality were higher CPA values (HR = 1.04, 95% CI 1.02‐1.04) and advanced fibrosis (HR = 2.80, 95% CI 1.29‐6.05) with similar results in standard and competing risk multivariable Cox regression analysis. In early/compensated ALD, CPA was the only independent predictor of hepatic decompensation and liver‐related death (HR = 1.08, 95% CI 1.06‐1.11). In the prospective cohort, we validated that CPA independently predicts hepatic decompensation in early/compensated ALD. The predictive power of CPA and LSM was equally strong.ConclusionsCPA predicts liver‐related mortality in ALD and hepatic decompensation and/or liver‐related death in early/compensated ALD. Traditional histological assessment may benefit from the addition of CPA to the evaluation of ALD.

Funder

Hellenic Society of Gastroenterology

Novo Nordisk Fonden

National Institute for Health Research

Horizon 2020

National Health and Medical Research Council

Syddansk Universitet

Odense Universitetshospital

UCLH Biomedical Research Centre

Publisher

Wiley

Subject

Pharmacology (medical),Gastroenterology,Hepatology

Reference36 articles.

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2. World Health Organization.Global status report on alcohol and health. Geneva2018.

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4. Liver cirrhosis

5. Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study

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