Hepatic, Gastrointestinal, Pulmonary and Renal Pharmacology

Serum biomarkers combined with ultrasonography for early diagnosis of non-alcoholic fatty liver disease confirmed by magnetic resonance spectroscopy

Authors: Ling-ling Qian1,2, Liang Wu1, Lei Zhang1,2, Jing Zhang1,2, Jia Zhou3, Yue-hua Li3, Qi-chen Fang1, Hua-ting Li1, Wei-ping Jia1
1 Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center of Diabetes, Shanghai 200233, China
2 Department of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
3 Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
Correspondence to: Hua-ting Li: huarting99@sjtu.edu.cn, Wei-ping Jia: wpjia@sjtu.edu.cn,
DOI: 10.1038/s41401-019-0321-x
Received: 6 June 2019
Accepted: 17 October 2019
Advance online: 27 November 2019


Magnetic resonance spectroscopy (MRS) is notably accurate for even minimal degree of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). But routine use of MRS is limited by its cost and availability. In this study, we developed a diagnostic model combining ultrasonography with biomarkers to identify mild NAFLD, with MRS as the reference standard. A total of 422 eligible subjects were enrolled. The serum levels of fibroblast growth factor 21 (FGF21), cytokeratin 18 M65ED, proteinase 3, neutrophil elastase, alpha-1 antitrypsin, and neutrophil elastase/alpha-1 antitrypsin were measured using ELISA assays. We found that among the six biomarkers, only serum FGF21 was independently associated with intrahepatic triglyceride content (IHTC, standardized β = 0.185, P< 0.001) and was an independent risk factor for mild NAFLD. Thus, we established a Mild NAFLD Model based on FGF21, alanine transaminase, triglycerides, and body mass index. The area under the receiver-operating characteristic curve of the Mild NAFLD Model was 0.853 (95% confidence interval: 0.816–0.886). Furthermore, a two-step approach combining ultrasonography with the Mild NAFLD Model displayed a better sensitivity for diagnosing mild NAFLD compared with each method alone, with a sensitivity of 97.32% and a negative predictive value of 85.48%. This two-step approach combining ultrasonography and the Mild NAFLD Model derived from serum FGF21 improves the diagnosis of mild NAFLD and can be applied to the early diagnosis of NAFLD in clinical practice.
Keywords: fatty liver; non-alcoholic fatty liver disease; biomarkers; diagnostic model; fibroblast growth factor 21; ultrasonography; magnetic resonance spectroscopy

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