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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Resumé

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.

OriginalsprogEngelsk
TidsskriftHepatology (Baltimore, Md.)
Vol/bind69
Udgave nummer3
Sider (fra-til)1075-1086
ISSN0270-9139
DOI
StatusUdgivet - mar. 2019

Fingeraftryk

Confidence Intervals
Collagen Type III
Liver
Platelet Count
ROC Curve
Liver Cirrhosis
Odds Ratio
beryllium trifluoride

Citer dette

Daniels, Samuel J ; Leeming, Diana J ; Eslam, Mohammed ; Hashem, Ahmed M ; Nielsen, Mette J ; Krag, Aleksander ; Karsdal, Morten A ; Grove, Jane I ; Guha, Indra Neil ; 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. I: Hepatology (Baltimore, Md.). 2019 ; Bind 69, Nr. 3. s. 1075-1086.
@article{f582141406554280b944a503d600d4ce,
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 Guha, {Indra Neil} 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",
note = "{\circledC} 2018 by the American Association for the Study of Liver Diseases.",
year = "2019",
month = "3",
doi = "10.1002/hep.30163",
language = "English",
volume = "69",
pages = "1075--1086",
journal = "Hepatology",
issn = "0270-9139",
publisher = "JohnWiley & Sons, Inc.",
number = "3",

}

Daniels, SJ, Leeming, DJ, Eslam, M, Hashem, AM, Nielsen, MJ, Krag, A, Karsdal, MA, Grove, JI, Guha, IN, 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 (Baltimore, Md.), bind 69, nr. 3, s. 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; Guha, Indra Neil; Kawaguchi, Takumi; Torimura, Takuji; McLeod, Duncan; Akiba, Jun; Kaye, Philip; de Boer, Bastiaan; Aithal, Guruprasad P; Adams, Leon A; George, Jacob.

I: Hepatology (Baltimore, Md.), Bind 69, Nr. 3, 03.2019, s. 1075-1086.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 - Guha, Indra Neil

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

N1 - © 2018 by the American Association for the Study of Liver Diseases.

PY - 2019/3

Y1 - 2019/3

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.

U2 - 10.1002/hep.30163

DO - 10.1002/hep.30163

M3 - Journal article

VL - 69

SP - 1075

EP - 1086

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 3

ER -