ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis
Open accessAbstract
Given the high global prevalence of nonalcoholic fatty liver disease (NAFLD), the need for relevant noninvasive 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. We measured PRO-C3 by enzyme-linked immunosorbent assay 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, and platelet count (ADAPT) was developed. PRO-C3 increased with fibrosis stage (Rho 0.50; P < 0.0001) and was independently associated with advanced fibrosis (odds ratio = 1.05; 95% confidence interval [CI] 1.02-1.08; P = 0.003). ADAPT showed areas under the receiver operating characteristics curve of 0.86 (95% CI 0.79-0.91) in the derivation and 0.87 in the validation cohort (95% CI 0.83-0.91) for advanced fibrosis. This was superior to the existing fibrosis scores, aspartate aminotransferase 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.
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- Authors
- Daniels, S. J., Leeming, D. J., Eslam, M., Hashem, A. M., Nielsen, M. J., Krag, A., Karsdal, M. A., Grove, J. I., Neil Guha, I., Kawaguchi, T., Torimura, T., McLeod, D., Akiba, J., Kaye, P., de Boer, B., Aithal, G. P., Adams, L. A., & George, J.
- Affiliations
- University of Southern Denmark (DK)
- Nordic Bioscience (Denmark) (DK)
- The University of Sydney (AU)
- Minia University (EG)
- Nottingham University Hospitals NHS Trust (GB)
- Nottingham Digestive Diseases Centre,University of Nottingham,Nottingham,United Kingdom
- Kurume University (JP)
- Westmead Hospital (AU)
- Department of Anatomical Pathology, PathWest,Fiona Stanley Hospital,Murdoch,Australia
- The University of Western Australia (AU)
- Corresponding author
- Daniels, Samuel J.
- ORCID
- Venue
- Hepatology
- Published
- 2019-02-27
- Volume
- 69
- Issue
- 3
- Pages
- 1075-1086
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- OpenAlex
- W2884076688
- Cited by
- 273
- References
- 47
- Citations by year
- 2026: 32 · 2025: 31 · 2024: 35 · 2023: 40 · 2022: 32 · 2021: 39 · 2020: 38 · 2019: 21 · 2018: 4
- FWCI
- 19.91
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, other-oa)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Nottingham ePrints (University of Nottingham) (submittedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Funders
- National Research Foundation
- Danmarks Grundforskningsfond
- Forsknings- og Innovationsstyrelsen
- Medical Research Council (MR/N005953/1)
- Danish Agency for Science and Higher Education
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- non-alcoholic fatty liver disease, advanced liver fibrosis, PRO-C3, type III collagen, noninvasive fibrosis assessment, non-invasive biomarkers, APRI, FIB-4, NAFLD fibrosis score, platelet count, diabetes mellitus
- MeSH terms
- Adult, Algorithms, Biopsy, Complement C3, Female, Humans, Liver Cirrhosis, Male, Middle Aged, Severity of Illness Index, Cohort Studies, Non-alcoholic Fatty Liver Disease
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