This study assessed the ability of 15 commonly used, non-invasive obesity and lipid-related indices to predict NAFLD risk in the general population. The accuracy of ABSI in predicting individual NAFLD risk was limited in both males and females, while the other 14 markers showed better predictive performance for NAFLD, especially in females. Of mention, although there were some differences in the predictive performance of the 15 obesity and lipid-related indices among different populations, TyG index-related parameters were superior to other parameters in predicting NAFLD in most populations. Therefore, TyG-related parameters may be the best choice for NAFLD risk screening indicators in the general population.
Past studies have shown that obesity, metabolic disorders, and environmental factors all contribute to the occurrence and development of NAFLD. However, with the rapid development of society, changes in lifestyle, dietary structure, and the prevalence of obesity, the prevalence of NAFLD is increasing rapidly, bringing a series of adverse consequences [6,7,8]. Therefore, it is an urgent task to screen vulnerable groups for NAFLD as soon as possible. Because liver biopsy-based tests are invasive, expensive, and time-consuming, noninvasive methods are being widely studied as alternative indicators [10, 11]. Simple measurements such as WC, BMI, WHtR, and blood lipids have an independent correlation with NAFLD [12, 16, 17]. These findings were verified in this study. Compared with WC, WHtR, and TG, BMI was a better predictor of NAFLD. In addition, it is worth mentioning that in this study, the AUC of BMI in most subgroups was greater than 0.8, which means that BMI had a good predictive performance in most populations. Although the incorporation of TyG significantly improves the predictive value of NAFLD in most subgroups, considering the simplicity and convenience of BMI measurement, it does not require additional laboratory measurements, so it should also be considered in the general population.
TyG index is a combination of FPG and TG. Previous studies reported that the index can be used as a substitute marker for IR in the clinic [29,30,31]. Additionally, it can effectively identify NAFLD and evaluate the risk of NAFLD in females [13, 32]. This finding was further verified in the present study. ROC analysis found that the AUC of TyG index for predicting NAFLD was 0.8186 in females and 0.7458 in males. Additionally, the TyG index has better predictive performance in the young population (age 18–30 years, AUC=0.9391 for females; AUC=0.8480 for males). TyG index-related parameters are the combined parameters of the TyG index with WC, BMI, and WHtR, which were first reported by Ko et al. [33]. They pointed out that TyG index-related parameters had the highest AUC value for predicting IR compared to visceral obesity indicators, lipid parameters, lipid ratios, and adipokines. Subsequent studies showed that TyG index-related parameters were used to predict non-obese, overweight, and obese people's NAFLD better than TyG alone [14, 24, 33]. This study expands the sample size from a previous study and found that TyG index-related parameters have excellent prediction performance in most populations.
TG/HDL-C is the ratio of TG and HDL-C. Similar to the TyG index, the TG/HDL-C ratio can distinguish IR from NAFLD, which has been widely popularized in the clinic [15, 34]. According to Ko et al., the TG/HDL-C ratio is a better predictor of IR than lipid markers and adipokines alone, but its AUC was lower than that of TyG-BMI, VAI, TyG index, LAP, and TyG-WC [32]. Similar results were found in predicting NAFLD in this study, which may be closely related to IR [1, 35].
HSI is a NAFLD prediction model developed by Lee et al [18]. It is a combination of liver enzymes and BMI, and was confirmed in a large number of studies to have excellent predictive performance in predicting NAFLD [36, 37]. According to a recent report by Lin et al., HSI has better prediction performance for NAFLD than BMI, WHtR, LAP, BRI, COI, VAI, TyG index, waist-hip ratio, body adiposity index (BAI) and abdominal volume index (AVI) [21]. However, it is not clear whether TyG index-related parameters are better than HSI and other obesity and lipid-related indices in predicting NAFLD. In this context, the predictive performance of 15 common obesity and lipid-related indices for NAFLD were compared in this study. The results showed that HSI did have better NAFLD identification ability than other parameters, but TyG index-related parameters were better predictors of NAFLD than HSI. In a follow-up study, the Procino team analyzed the predictive value of HSI, WC, fatty liver index, BMI, waist/height0.5, AVI, WHtR, and BRI for NAFLD. Their findings contradicted the research of Lin et al., who found that the best indicator of NAFLD screening was AVI, not HSI [22]. Additionally, in a recent study, Zhang et al. evaluated the predictive value of relative fat mass, WC, ABSI, WHtR, COI, ponderal index, BMI, and LAP for NAFLD in the elderly; their study showed that LAP was the best marker of these parameters for predicting NAFLD [23]. This study confirms the conclusion of Zhang et al., and in further analysis, it was found that LAP was superior to the TyG index, WHtR, ABSI, COI, BMI, TG/HDL-C ratio, WC, VAI, TG, and BRI in both males and females. Additionally, it is worth noting that LAP was the best predictor of NAFLD for young females (age 18–30 years, AUC=0.9801). Compared with these previous studies, this study considered more obesity and lipid-related indices, as well as TyG index-related parameters, which have been widely considered recently [14, 24]. In general, TyG index-related parameters may be the best choice for NAFLD risk screening in the general population, whether male or female, whether young, middle-aged or elderly. More importantly, the indicators that make up the TyG index-related parameters are clinically easy to obtain and affordable, which brings great convenience for the prevention and treatment of NAFLD.
In the correlation analysis, the researchers calculated the OR value and 95% CI of the corresponding NAFLD risk after Z-conversion of 15 obesity and lipid-related indices. The results of the study were similar to the results of the ROC analysis. Among the 15 parameters, TyG index-related parameters had the strongest correlation with NAFLD risk, both before and after model adjustment. Although many parameters in this study have a strong correlation with NAFLD and the accuracy of predicting NAFLD was good, the TyG index-related parameters were best.
In this study, the best thresholds of TyG index-related parameters in different sex and different age groups were calculated by ROC analysis, in which the best thresholds of TyG-WHtR, TyG-WC, and TyG-BMI were 3.8078, 595.3694, and 178.7047 in females, respectively and 4.0945, 699.2287, and 196.8688 in males, respectively. Two previous studies also provided data for reference; in the study by Huang et al., the best threshold for TyG-BMI to predict NAFLD in non-obese people was 183.8263 [24]. Khamseh's team reported that the best threshold for NAFLD corresponding to TyG-WC in overweight and obese individuals was 876 [14], which was significantly higher than the best threshold recommended in this study. In view of the obvious differences among the study subjects, only a brief description and report of these results are provided as a reference for subsequent studies.
Study strength and limitations
Several positive effects should be noted. First, the biggest advantage of this study is that of the 15 obesity and lipid-related indices, TyG index-related parameters had the highest accuracy for predicting NAFLD. Second, this study is based on data analysis of a large sample, and the conclusion can be regarded as relatively reliable. Finally, the study was stratified by sex and age to identify the best parameters and thresholds for predicting NAFLD for different populations. These results provide a reliable reference for precision treatment.
The study has some limitations. First, this study lacks general measurement information such as hip/neck circumference. To our knowledge, the new index combining the TyG index with hip/neck circumference was recently found to have high diagnostic value for IR [38]. IR is the main mediating factor in the pathogenesis of NAFLD [1], and the combination of the TyG index and hip/neck circumference may have excellent performance in the prediction of NAFLD. In addition, due to the lack of hip circumference, AVI and BAI cannot be calculated, so it was not possible to further evaluate the difference in NAFLD between AVI, BAI, and other obesity and lipid-related indices. Second, the diagnosis of NAFLD was made only on the basis of ultrasound. Although the current ultrasound diagnosis has high sensitivity and specificity, it is undeniable that nearly 30% of mild fatty liver may be missed [39], which means that the true prevalence rate of NAFLD in this study may be higher. Third, because the dataset analyzed comes from a public database, the dataset provided in the database cannot be updated, which lacks some parameters used to calculate the score of non-invasive fibrosis. Therefore, unfortunately, staging information on liver fibrosis cannot be provided in the current study. Fourth, the study used data from the Japanese population, so its conclusions may not apply to other ethnic groups. Finally, the research design may be a limitation. The cross-sectional design adopted in this study restricts us from explaining the causal correlation of these variables.