In this study, we aimed to evaluate the ability of FLI and HSI, based on simple clinical parameters, to detect NAFLD in a group of OSAHS patients. The major finding was that both FLI and HSI could be valuably screened NAFLD in OSAHS patients. The FLI showed better performance in terms of higher AUROC in diagnosing NAFLD than HSI. The respective optimal cut-off value of FLI and HSI to discriminate NAFLD in OSAHS patients was 60 and 35, with acceptable sensitivity and specificity.
Several studies evaluating diagnostic performance of FLI and HSI have been conducted in Europe and Asia. A study including 228 subjects with ultrasound diagnosis of fatty liver and 268 subjects without fatty liver showed that an FLI <30 can be used to rule out (sensitivity 87%; negative likelihood ratio 0.2) and an FLI ≥60 to rule in hepatic steatosis (specificity 86%; positive likelihood ratio 4.3). Yang et al enrolled 29,797 consecutive subjects who received health check-up services and showed that FLI had the best discriminative ability to identify patients with ultrasonographic fatty liver with an AUROC of 0.827. A retrospective cross-sectional study performed in western China found that AUROC of FLI for predicting NAFLD was 0.880 (95% CI 0.874–0.886). The ROC analysis showed that the optimal cut-off value for FLI in diagnosing NAFLD was 30.420 with sensitivity 83% and specificity 77%. With respect to HSI, a cross-sectional study with 10,724 health check-up subjects reported that HSI had an AUROC of 0.812 (95% CI 0.801–0.824). At values of <30.0 or >36.0, HSI ruled out NAFLD with a sensitivity of 93%, or detected NAFLD with a specificity of 92%, respectively. Zhu et al found that AUROC of FLI was significantly higher than that of HSI. Another study focusing on patients with type 1 diabetes also found that the diagnostic performance of FLI (AUROC 0.860) was better than HSI (AUROC 0.750).
Accumulating evidence has shown that OSAHS is an independent risk factor of NAFLD. Our previous studies demonstrated that OSAHS was independently associated with liver steatosis and elevation of serum aminotransferases. Serum ALT declined significantly after 3 months of CPAP treatment. Aron-Wisnewsky et al studied 101 subjects getting bariatric surgery and found that hypoxic burden was independently predictive of liver fibrosis and NAFLD activity score. A recent study including 124 patients suspected OSAHS suggested a dose-response relationship between OSAHS severity and liver stiffness. Severe OSAHS was independently associated with significant fibrosis. High prevalence of OSAHS was also found in OSAHS patients.[11,12] A study found that the prevalence of ultrasound diagnosis of NAFLD was up to 83% in 137 subjects who underwent PSG for suspected OSAHS. While another study showed that prevalence of liver steatosis was 66% and 83% in mild to moderate and severe OSAHS patients, respectively.
Based on the close relationship between OSAHS and NAFLD and the evidence of high prevalence of NAFLD in OSAHS patients, our study focused on OSAHS patients and showed that the AUROC of FLI and HSI for predicting NAFLD was 0.802 and 0.753, respectively. The performance of FLI and HSI in our pilot study was weaker as compared to that described by other studies.[13,14,21] However, another study indicated that the AUROC for FLI and HSI in detecting liver steatosis were found to be low (FLI 0.647 and HSI 0.637) in 220 patients with type 2 diabetes. Factors such as ethnicity, morbidities, method for diagnosis of liver steatosis, sample size, and different prevalence of NAFLD could be responsible for different diagnostic efficacy of the indices. Consistent with other studies,[17,22] we demonstrated that performance of FLI tended to be better than HSI in identifying NAFLD. In the present study, the best cut-off value of FLI and HSI was 60 (sensitivity 66% and specificity 80%) and 35 (sensitivity 81% and specificity 60%), respectively. Consistent with the results of the present study, our previous study with a group population with OSAHS showed that the best cut-off value of FLI was 60 in diagnosing NAFLD.
An FLI <30 was suggested to be used to rule out NAFLD with sensitivity 87% and specificity 64% by Bedogni et al At a value of <30.0, HSI could rule out NAFLD with a sensitivity 91% and specificity 40%. Our study showed that sensitivity and specificity of FLI <30 for predicting absence of NAFLD were 95% and 36%, respectively. Sensitivity and specificity of HSI <30 for predicting absence of NAFLD were 98% and 21%, respectively. Both indices showed high sensitivity, while the specificity was relatively low. If they are to be used to screen the NAFLD, it should be further evaluated carefully combining with other factors.
Even though the gold standard in the diagnosis of NAFLD is liver biopsy, it is not routinely performed because it is an invasive and expensive tool. Currently, the diagnosis of NAFLD is usually made by ultrasonography in a clinical setting. Compared with ultrasonography, the indices have several advantages. First, FLI is a feasible marker that involves four clinical available parameters, and it is easily calculated in an office setting. It is easier to access in comparing with ultrasonography. Second, it is more cost-effective; it is reported to cost only 20 Yuan per capita to obtain the results of all parameters. The application of these indices may help the selection of a potential population before imaging tests, which lowers the cost. Third, it is a quantitative method for the evaluation of fatty liver disease, while ultrasonography is a semi-quantitative method. Lastly, FLI could be applied not only for screening fatty liver disease, but also has been increasingly used to be a maker to predict atherosclerotic lesions, cardiovascular and non-cardiovascular mortality as well as all-cause mortality.[15,16,28,29]
This study has several limitations that are worth noting. First, a selection bias is possible because subjects were recruited from among individuals who were presented to our sleep laboratories due to symptoms of sleep apnea and were diagnosed as OSAHS by PSG. Second, ultrasonography was used as a diagnostic tool for NAFLD, lacking data of the liver biopsy in our study. Previous studies reported that its sensitivity decreased while hepatic steatosis was less than 20% to 30%.[30,31] Third, the severity of hepatic steatosis was not accessed, which restrained us to find specific cut-offs for steatosis quantification in OSAHS patients with NAFLD. Fourth, compared with the sample size of other studies which focused on general population, the sample size of the present study was relatively small. However, we only focused on the OSAHS population diagnosed based on PSG and included the patients at two sleep laboratories. Lastly, ultrasonography was not performed by a single ultrasound technician. There may have been intra-operator and inter-operator variability in interpreting fatty liver on ultrasonography despite the same criteria.
In conclusion, both FLI and HSI can serve as screening tools for NAFLD in OSAHS patients. The FLI shows better performance in diagnosing NAFLD than HSI. The respective optimal FLI and HSI cut-off value to discriminate NAFLD in OSAHS patients is 60 and 35, with an acceptable sensitivity and specificity.
This work was supported by the grants from the Youth Research Fund from Fujian Provincial Health Bureau (No. 2015-1-98) and Startup Fund for Scientific Research from Fujian Medical University (No. 2017XQ1117).
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