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

• Published in: Alimentary pharmacology & therapeutics Vol. 49; no. 9; pp. 1214 - 1222
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.05.2019
• Subjects: Adult; Aged; Biomarkers - analysis; Biomarkers - metabolism; Biopsy; Cirrhosis; Clinical outcomes; Clinical trials; Collagen; Collagen (type I); Collagen - analysis; Collagen - metabolism; decompensation; Fatty liver; Female; fibroscan; Fibrosis; Follow-Up Studies; Greece - epidemiology; Humans; Liver; Liver - chemistry; Liver - metabolism; Liver - pathology; Liver cirrhosis; Liver Cirrhosis - diagnosis; Liver Cirrhosis - metabolism; Liver Cirrhosis - mortality; Liver Cirrhosis - therapy; Liver diseases; Liver Transplantation; Longitudinal Studies; Male; Middle Aged; Non-alcoholic Fatty Liver Disease - diagnosis; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - mortality; Non-alcoholic Fatty Liver Disease - therapy; Prognosis; Regression analysis; Retrospective Studies; steatohepatitis; Sweden - epidemiology; Treatment Outcome; United Kingdom - epidemiology; Greece; United Kingdom; Sweden; steatohepatitis; fibrosis; fibroscan; prognosis; decompensation
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.15219

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.