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.

磁共振波谱（MRS）在非酒精性脂肪肝疾病（NAFLD）中即使对于最小程度的肝脂肪变性也非常准确。但是MRS的常规使用受到其成本和可用性的限制。在这项研究中，我们开发了一种结合了超声检查和生物标记物以轻度NAFLD的诊断模型，并以MRS作为参考标准。共有422名合格受试者入选。使用ELISA法测定了成纤维细胞生长因子21（FGF21），细胞角蛋白18 M65ED，蛋白酶3，中性粒细胞弹性蛋白酶，α-1抗胰蛋白酶和中性粒细胞弹性蛋白酶/α-1抗胰蛋白酶的血清水平。我们发现，在这六个生物标志物中，只有血清FGF21与肝内甘油三酸酯含量独立相关（IHTC，标准β  = 0.185，P  < 0.001），是轻度NAFLD的独立危险因素。因此，我们基于FGF21，丙氨酸转氨酶，甘油三酸酯和体重指数建立了轻度NAFLD模型。轻度NAFLD模型的接收器操作特征曲线下的面积为0.853（95％置信区间：0.816-0.886）。此外，与超声检查和轻度NAFLD模型相结合的两步法显示，与单独使用每种方法相比，诊断轻度NAFLD的灵敏度更高，灵敏度为97.32％，阴性预测值为85.48％。这种将超声检查和源自血清FGF21的轻度NAFLD模型相结合的两步方法改善了轻度NAFLD的诊断，可在临床实践中应用于NAFLD的早期诊断。