Combined Serum Biomarkers in Non-Invasive Diagnosis of Non-Alcoholic Steatohepatitis

Non-alcoholic steatoheaptitis (NASH), the critical stage of non-alcoholic fatty liver disease (NAFLD), is of chronic progression and can develop cirrhosis even hepatocellular carcinoma (HCC). However, non-invasive biomarkers for NASH diagnosis remain poorly applied in clinical practice. Our study ai...

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Bibliographic Details
Published in:PloS one 2015-06, Vol.10 (6), p.e0131664-e0131664
Main Authors: Yang, Mei, Xu, Dongping, Liu, Yuan, Guo, Xiaodong, Li, Wenshu, Guo, Chaonan, Zhang, Hongping, Gao, Yinjie, Mao, Yuanli, Zhao, Jingmin
Format: Article
Language:English
Subjects:
Accuracy
Adult
Biocompatibility
Bioindicators
Biological markers
Biomarkers
Biomarkers - blood
Biomedical materials
Biopsy
Case-Control Studies
Cirrhosis
Clinical trials
Cytokeratin
Cytokines
Development and progression
Diabetes
Diagnosis
Enzyme-linked immunosorbent assay
Enzymes
Epithelium
Fatty liver
Female
Fibroblast growth factors
Fibroblasts
Gastroenterology
Growth factors
Health care
Hepatitis
Hepatitis B
Hepatitis C
Hepatitis C virus
Hepatocellular carcinoma
Hepatology
Hospitals
Humans
Interleukin 1
Interleukin 1 receptor antagonist
Interleukin 1 receptors
Keratin
Liver
Liver cancer
Liver cirrhosis
Liver diseases
Logistic Models
Male
Medical diagnosis
Metabolism
Multivariate Analysis
Non-alcoholic Fatty Liver Disease - blood
Non-alcoholic Fatty Liver Disease - diagnosis
Obesity
Osteoprotegerin
Pathology
Patients
Pigment epithelium-derived factor
Reproducibility of Results
ROC Curve
Rodents
Serum levels
Viruses
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Description
Summary:Non-alcoholic steatoheaptitis (NASH), the critical stage of non-alcoholic fatty liver disease (NAFLD), is of chronic progression and can develop cirrhosis even hepatocellular carcinoma (HCC). However, non-invasive biomarkers for NASH diagnosis remain poorly applied in clinical practice. Our study aims at testing the accuracy of the combination of cytokeratin-18 M30 fragment (CK-18-M30), fibroblast growth factor 21 (FGF-21), interleukin 1 receptor antagonist (IL-1Ra), pigment epithelium-derived factor (PEDF) and osteoprotegerin (OPG) in diagnosing NAFLD and NASH. 179 patients with biopsy-proven NAFLD were enrolled as training group, 91 age- and gender-matched healthy subjects were recruited at the same time as controls. 63 other NAFLD patients were separately collected as validation group. 45 alcoholic fatty liver disease (AFLD) patients, 50 hepatitis B virus (HBV) patients, 52 hepatitis C virus (HCV) patients were also included. Serum biomarker levels were measured by enzyme-linked immunosorbent assay. Serum levels of CK-18-M30, FGF-21, IL-1Ra and PEDF increased, while OPG decreased in a stepwise fashion in controls, non-NASH NAFLD patients and NASH patients (P < 0.01). The area under receiver-operating characteristics curve to diagnose NASH was 0.86 for CK-18-M30, 0.89 for FGF-21, 0.89 for IL-1Ra, 0.89 for PEDF and 0.89 for OPG. CK-18-M30 had 70% negative predictive value (NPV) and 79% positive predictive value (PPV) to diagnose NASH. A 5-step approach measuring CK-18-M30 followed by FGF21, IL-1Ra, PEDF and OPG gradually improved the NPV to 76% and PPV to 85%, which reached 80% and 76% respectively in the validation cohort. Compared to single biomarker, stepwise combination of CK-18-M30, FGF-21, IL-1Ra, PEDF and OPG can further improve the accuracy in diagnosing NASH.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0131664