Prediction of Nonalcoholic Fatty Liver Disease Using Noninvasive and Non-Imaging Procedures in Japanese Health Checkup Examinees

Abstract

Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual alcohol drinking were included. Fatty liver was diagnosed by ultrasonography. The hepatic steatosis index (HSI), Zhejiang University (ZJU) index, and fatty liver index (FLI) were determined, and risk of advanced liver fibrosis was evaluated by the fibrosis-4 index. NAFLD was diagnosed in 1935 (28.0%) of the 6927 subjects. The area under the receiver operating characteristic (AUROC) curve of the HSI, ZJU index, and FLI was 0.874, 0.886, and 0.884, respectively. The AUROC of the ZJU index (p < 0.001) and FLI (p = 0.002) was significantly greater than that for the HSI. In subjects with a high risk of advanced fibrosis, the sensitivity of the HSI, ZJU index, and FLI were 88.8%, 94.4%, and 83.3% with a low cut-off value and the specificity was 98.5%, 100%, and 100% with a high cut-off value. In conclusion, all indexes were useful to diagnose NAFLD in the general Japanese population and in subjects with potentially advanced liver fibrosis.

Keywords: ROC; fatty liver index; fibrosis-4 index; health checkup; hepatic steatosis index; nonalcoholic fatty liver disease; ultrasonography.

Figure 1

Frequency distribution of the HSI, ZJU index, and FLI. Graphs represent the frequency distribution of the HSI, ZJU index, and FLI. Orange lines represent cut-off values: 30 and 36 for the HSI, 32 and 38 for the ZJU index, and 30 and 60 for the FLI. The percentages in the graphs represent the proportion of subjects in each range. FLI, fatty liver index; HSI, hepatic steatosis index; ZJU, Zhejiang University.

Figure 2

ROC curve of the HSI, ZJU index, and FLI for detecting NAFLD. ROC curve of the HSI (red), ZJU index (green) and FLI (blue) for the diagnosis of NAFLD in overall subjects. The ZJU index and FLI showed a greater area under the ROC curve than the HSI. * p < 0.05 in the comparison between the ZJU index and HSI. ^† p < 0.05 in the comparison between the FLI and HSI by the DeLong test. AUROC, area under the receiver operating characteristic; FLI, fatty liver index; HSI, hepatic steatosis index; NAFLD, nonalcoholic fatty liver disease; ROC, receiver operating characteristic; ZJU, Zhejiang University.

Figure 3

ROC curve of the HSI, ZJU index, and FLI for detecting NAFLD. ROC curve of the HSI (red), ZJU index (green) and FLI (blue) for the diagnosis of NAFLD stratified by the risk of advanced liver fibrosis (stage 3 or severe) evaluated using the FIB-4 index. (a) Low risk (FIB-4 index < 1.3); (b) intermediate risk (FIB-4 index 1.3–2.67); (c) high risk (FIB-4 index > 2.67). The ZJU index and FLI showed a greater AUROC than the HSI in low risk and the ZJU index showed a greater AUROC than the HSI in intermediate risk. * p < 0.05 in comparison between the ZJU index and HSI. ^† p < 0.05 in the comparison between FLI and HSI by the DeLong test. AUROC, area under the receiver operating characteristic; FIB-4, fibrosis 4; FLI, fatty liver index; HSI, hepatic steatosis index; NAFLD, nonalcoholic fatty liver disease; ROC, receiver operating characteristic; ZJU, Zhejiang University.

Figure 4

Comparison between the ZJU index and FLI under specific conditions. ROC curve of the ZJU index (red) and FLI (blue) for diagnosis of NAFLD. The ZJU index and FLI were compared in (a) females, (b) males, (c) subjects without diabetes, (d) subjects with diabetes, (e) subjects with ALT within the reference range (≤30 U/L), and (f) subjects with ALT > 30 U/L. The ZJU index showed a greater AUROC than the FLI when the subjects were stratified by gender. The FLI showed a greater AUROC than the ZJU index in the patients with diabetes. * p < 0.05. ** p < 0.001 by the DeLong test. AUROC, area under the receiver operating characteristic; FLI, fatty liver index; NAFLD, nonalcoholic fatty liver disease; ZJU, Zhejiang University.