Mads Israelsen1,2,3, Marta Guerrero Misas1, Anastasios Koutsoumourakis1, Yi Huang4, Maja Thiele2,3, Andrew Hall5, Ditlev Rasmussen2,3, Claudia Covelli6, Elena Buzzetti1, Laura Iogna Prat1, Davide Roccarina1, Sönke Detlefsen3,7, Tu Vinh Luong5, Alberto Quaglia5, Aleksander Krag2,3, Gary Jeffrey4, Massimo Pinzani1, Emmanuel A Tsochatzis1. 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
BACKGROUND: No 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. AIM: To assess the predictive value of CPA on hepatic decompensation and liver-related mortality in ALD METHODS: In 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). RESULTS: In 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. CONCLUSIONS: CPA 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.
BACKGROUND: No 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. AIM: To assess the predictive value of CPA on hepatic decompensation and liver-related mortality in ALD METHODS: In 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). RESULTS: In 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. CONCLUSIONS:CPA 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.
Authors: Philipp Königshofer; Benedikt Silvester Hofer; Ksenia Brusilovskaya; Benedikt Simbrunner; Oleksandr Petrenko; Katharina Wöran; Merima Herac; Judith Stift; Katharina Lampichler; Gerald Timelthaler; David Bauer; Lukas Hartl; Bernhard Robl; Maria Sibila; Bruno K Podesser; Georg Oberhuber; Philipp Schwabl; Mattias Mandorfer; Michael Trauner; Thomas Reiberger Journal: Hepatology Date: 2021-12-20 Impact factor: 17.298
Authors: David Marti-Aguado; Matías Fernández-Patón; Clara Alfaro-Cervello; Claudia Mestre-Alagarda; Mónica Bauza; Ana Gallen-Peris; Víctor Merino; Salvador Benlloch; Judith Pérez-Rojas; Antonio Ferrández; Víctor Puglia; Marta Gimeno-Torres; Victoria Aguilera; Cristina Monton; Desamparados Escudero-García; Ángel Alberich-Bayarri; Miguel A Serra; Luis Marti-Bonmati Journal: Biomolecules Date: 2021-12-02