ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis
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, a...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Wiley
2018
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| Online Access: | https://eprints.nottingham.ac.uk/52968/ |
| _version_ | 1848798849967063040 |
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| author | 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. George, Jacob |
| author_facet | 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. George, Jacob |
| author_sort | Daniels, Samuel J. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:26:19Z |
| format | Article |
| id | nottingham-52968 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:26:19Z |
| publishDate | 2018 |
| publisher | Wiley |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-529682024-08-15T15:30:32Z https://eprints.nottingham.ac.uk/52968/ 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. George, Jacob 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. Wiley 2018-07-04 Article PeerReviewed 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) Biomarker Extracellular matrix Non-invasive score Non-alcoholic fatty liver disease PRO-C3 |
| spellingShingle | Biomarker Extracellular matrix Non-invasive score Non-alcoholic fatty liver disease PRO-C3 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. George, Jacob ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis |
| title | ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis |
| title_full | ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis |
| title_fullStr | ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis |
| title_full_unstemmed | ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis |
| title_short | ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis |
| title_sort | adapt: an algorithm incorporating pro-c3 accurately identifies patients with nafld and advanced fibrosis |
| topic | Biomarker Extracellular matrix Non-invasive score Non-alcoholic fatty liver disease PRO-C3 |
| url | https://eprints.nottingham.ac.uk/52968/ |