Cited by 273Liver Disease Diagnosis and TreatmentLiver Disease and TransplantationLiver Diseases and Immunity

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

Open access
Daniels, Samuel J., Leeming, Diana J., Eslam, Mohammed, Hashem, Ahmed M., Nielsen, Mette J., Krag, Aleksander, Karsdal, Morten A., Grove, Jane I. +10 more·2019·Hepatology

Abstract

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.

Integrity signals

Registry

Crossref · 10.1002/hep.30163

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

The text we found for this paper looks like another document, so its claims and self-check weren’t run. The registry and citation checks still apply.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The text we found for this paper looks like another document, so the self-check wasn’t run.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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.
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review