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

Samuel J Daniels, Diana J Leeming, Mohammed Eslam, Ahmed M Hashem, Mette J Nielsen, Aleksander Krag, Morten A Karsdal, Jane I Grove, Indra Neil Guha, Takumi Kawaguchi, Takuji Torimura, Duncan McLeod, Jun Akiba, Philip Kaye, Bastiaan de Boer, Guruprasad P Aithal, Leon A Adams, Jacob George

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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.

Original languageEnglish
JournalHepatology (Baltimore, Md.)
Issue number3
Pages (from-to)1075-1086
Publication statusPublished - Mar 2019


Bibliographical note

© 2018 by the American Association for the Study of Liver Diseases.

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Daniels, S. J., Leeming, D. J., Eslam, M., Hashem, A. M., Nielsen, M. J., Krag, A., Karsdal, M. A., Grove, J. I., Guha, I. N., Kawaguchi, T., Torimura, T., McLeod, D., Akiba, J., Kaye, P., de Boer, B., Aithal, G. P., Adams, L. A., & George, J. (2019). ADAPT: An algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis. Hepatology (Baltimore, Md.), 69(3), 1075-1086.