ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis

Daniels, Samuel J., Leeming, Diana J., Eslam, Mohammed, Hashem, Ahmed M, Nielsen, Mette J., Krag, Aleksander, Karsdal, Morten A., Grove, Jane I., Guha, Indra Neil, Kawaguchi, Takumi, Torimura, Takuji, McLeod, Duncan, Akiba, Jun, Kaye, Philip, de Boer, Bastiaan, Aithal, Guruprasad P., Adams, Leon A. and George, Jacob (2018) ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis. Hepatology . ISSN 1527-3350 (In Press)

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Background and Aim: Given the high global prevalence of non-alcoholic fatty liver disease (NAFLD), the need for relevant non-invasive biomarkers and algorithms to accurately stage disease severity is a critical unmet medical need. Identifying those with advanced fibrosis (≥F3) is the most crucial, as these individuals have the greatest risk of adverse, long-term, liver-related outcomes. We aimed to investigate the role of PRO-C3 (a marker of type III collagen formation) as a biomarker for advanced fibrosis in NAFLD.

Methods: We measured PRO-C3 by enzyme-linked immunosorbent assay (ELISA) in two large independent cohorts with extensive clinical phenotyping and liver biopsy; 150 in the derivation and 281 in the validation cohort. A PRO-C3 based fibrosis algorithm that included Age, presence of DiAbetes, PRO-C3 (a marker of type III collagen formation), and plaTelet count (“ADAPT”) was developed. Results: PRO-C3 increased with fibrosis stage (rho 0.50 p<0.0001) and was independently associated with advanced fibrosis (OR=1.05, 95% CI 1.02-1.08, p= 0.003). ADAPT showed areas under the receiver operating characteristics curve (AUROC) of 0.86 (95% CI 0.79 to 0.91) in the derivation and 0.87 in the validation cohort (95% CI 0.83 to 0.91) for advanced fibrosis. This was superior to the existing fibrosis scores, aspartate aminotransferase (AST) to platelet ratio index (APRI), FIB-4 and NAFLD fibrosis score (NFS) in most comparisons.

Conclusion: PRO-C3 is an independent predictor of fibrosis stage in NAFLD. A PRO-C3 based score (ADAPT) accurately identifies patients with NAFLD and advanced fibrosis and is superior to APRI, FIB-4 and NFS.

Item Type: Article
Keywords: Biomarker, Extracellular matrix, Non-invasive score, Non-alcoholic fatty liver disease, PRO-C3
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Nottingham Digestive Diseases Centre
Depositing User: Jones, Natalie
Date Deposited: 17 Jul 2018 08:26
Last Modified: 17 Jul 2019 04:30

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