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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1075-1086
Number of pages12
JournalHepatology
Volume69
Issue number3
DOIs
Publication statusPublished - 1 Mar 2019

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Fibrosis
Confidence Intervals
Blood Platelets
Biomarkers
Non-alcoholic Fatty Liver Disease
Collagen Type III
Liver
Aspartate Aminotransferases
Transaminases
Platelet Count
ROC Curve
Liver Cirrhosis
Enzyme-Linked Immunosorbent Assay
Odds Ratio
Biopsy

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Daniels, S. J., Leeming, D. J., Eslam, M., Hashem, A. M., Nielsen, M. J., Krag, A., ... George, J. (2019). ADAPT: An Algorithm Incorporating PRO-C3 Accurately Identifies Patients With NAFLD and Advanced Fibrosis. Hepatology, 69(3), 1075-1086. https://doi.org/10.1002/hep.30163
Daniels, Samuel J. ; Leeming, Diana J. ; Eslam, Mohammed ; Hashem, Ahmed M. ; Nielsen, Mette J. ; Krag, Aleksander ; Karsdal, Morten A. ; Grove, Jane I. ; Neil Guha, Indra ; 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. In: Hepatology. 2019 ; Vol. 69, No. 3. pp. 1075-1086.
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Daniels, SJ, Leeming, DJ, Eslam, M, Hashem, AM, Nielsen, MJ, Krag, A, Karsdal, MA, Grove, JI, Neil Guha, I, Kawaguchi, T, Torimura, T, McLeod, D, Akiba, J, Kaye, P, de Boer, B, Aithal, GP, Adams, LA & George, J 2019, 'ADAPT: An Algorithm Incorporating PRO-C3 Accurately Identifies Patients With NAFLD and Advanced Fibrosis' Hepatology, vol. 69, no. 3, pp. 1075-1086. https://doi.org/10.1002/hep.30163

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.; Neil Guha, Indra; Kawaguchi, Takumi; Torimura, Takuji; McLeod, Duncan; Akiba, Jun; Kaye, Philip; de Boer, Bastiaan; Aithal, Guruprasad P.; Adams, Leon A.; George, Jacob.

In: Hepatology, Vol. 69, No. 3, 01.03.2019, p. 1075-1086.

Research output: Contribution to journalArticle

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AU - Daniels, Samuel J.

AU - Leeming, Diana J.

AU - Eslam, Mohammed

AU - Hashem, Ahmed M.

AU - Nielsen, Mette J.

AU - Krag, Aleksander

AU - Karsdal, Morten A.

AU - Grove, Jane I.

AU - Neil Guha, Indra

AU - Kawaguchi, Takumi

AU - Torimura, Takuji

AU - McLeod, Duncan

AU - Akiba, Jun

AU - Kaye, Philip

AU - de Boer, Bastiaan

AU - Aithal, Guruprasad P.

AU - Adams, Leon A.

AU - George, Jacob

PY - 2019/3/1

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N2 - 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.

AB - 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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Daniels SJ, Leeming DJ, Eslam M, Hashem AM, Nielsen MJ, Krag A et al. ADAPT: An Algorithm Incorporating PRO-C3 Accurately Identifies Patients With NAFLD and Advanced Fibrosis. Hepatology. 2019 Mar 1;69(3):1075-1086. https://doi.org/10.1002/hep.30163