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

doi:10.1002/hep.30163

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

Internal Medicine

Research output: Contribution to journal › Article › peer-review

144 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 language	English
Pages (from-to)	1075-1086
Number of pages	12
Journal	Hepatology
Volume	69
Issue number	3
DOIs	https://doi.org/10.1002/hep.30163
Publication status	Published - 1 Mar 2019

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10.1002/hep.30163

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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., Neil Guha, I., 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, 69(3), 1075-1086. https://doi.org/10.1002/hep.30163

@article{75c0637e305d4e5f8283ef7e367da5e1,

title = "ADAPT: An Algorithm Incorporating PRO-C3 Accurately Identifies Patients With NAFLD and Advanced Fibrosis",

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.",

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

year = "2019",

month = mar,

day = "1",

doi = "10.1002/hep.30163",

language = "English",

volume = "69",

pages = "1075--1086",

journal = "Hepatology",

issn = "0270-9139",

publisher = "John Wiley & Sons",

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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

TY - JOUR

T1 - ADAPT

T2 - An Algorithm Incorporating PRO-C3 Accurately Identifies Patients With NAFLD and Advanced Fibrosis

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

Y1 - 2019/3/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85061295644&partnerID=8YFLogxK

U2 - 10.1002/hep.30163

DO - 10.1002/hep.30163

M3 - Article

C2 - 30014517

AN - SCOPUS:85061295644

SN - 0270-9139

VL - 69

SP - 1075

EP - 1086

JO - Hepatology

JF - Hepatology

IS - 3

ER -

ADAPT: An Algorithm Incorporating PRO-C3 Accurately Identifies Patients With NAFLD and Advanced Fibrosis

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