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

被引:184
作者
Daniels, Samuel J. [1 ,2 ]
Leeming, Diana J. [1 ]
Eslam, Mohammed [3 ,4 ]
Hashem, Ahmed M. [5 ]
Nielsen, Mette J. [1 ]
Krag, Aleksander [2 ,6 ]
Karsdal, Morten A. [1 ]
Grove, Jane I. [7 ,8 ,9 ,15 ]
Guha, Indra Neil [7 ,8 ,9 ,15 ]
Kawaguchi, Takumi [10 ]
Torimura, Takuji [10 ]
McLeod, Duncan [11 ]
Akiba, Jun [12 ]
Kaye, Philip [7 ,15 ]
de Boer, Bastiaan [13 ]
Aithal, Guruprasad P. [7 ,8 ,9 ,15 ]
Adams, Leon A. [14 ]
George, Jacob [3 ,4 ]
机构
[1] Nord Biosci Biomarkers & Res AS, Herlev, Denmark
[2] Univ Southern Denmark, Inst Clin Res, Odense, Denmark
[3] Univ Sydney, Westmead Inst Med Res, Storr Liver Ctr, Westmead, NSW, Australia
[4] Westmead Hosp, Westmead, NSW, Australia
[5] Minia Univ, Dept Syst & Biomed Engn, Fac Engn, Al Minya, Egypt
[6] Odense Univ Hosp, Dept Gastroenterol & Hepatol, Odense, Denmark
[7] Univ Nottingham, Nottingham Digest Dis Ctr, Nottingham, England
[8] Nottingham Univ Hosp NHS Trust, NIHR Nottingham Biomed Res Ctr, Nottingham, England
[9] Univ Nottingham, Nottingham, England
[10] Kurume Univ, Dept Med, Sch Med, Kurume, Fukuoka, Japan
[11] Westmead Hosp, ICPMR, Dept Anat Pathol, Sydney, NSW, Australia
[12] Kurume Univ Hosp, Dept Diagnost Pathol, Kurume, Fukuoka, Japan
[13] Fiona Stanley Hosp, PathWest, Dept Anat Pathol, Murdoch, WA, Australia
[14] Univ Western Australia, Sch Med, Nedlands, WA, Australia
[15] Univ Nottingham, Nottingham Mol Pathol Node, MRC, Nottingham, England
基金
新加坡国家研究基金会;
关键词
FATTY LIVER-DISEASE; SIMPLE NONINVASIVE INDEX; NONALCOHOLIC STEATOHEPATITIS; STIFFNESS MEASUREMENT; DIAGNOSTIC-ACCURACY; BIOPSY; PREDICT; VARIABILITY; VALIDATION; MORTALITY;
D O I
10.1002/hep.30163
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:1075 / 1086
页数:12
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