Abstract Disclosure: J. Yoon: None. I. Hwang: None. Background: The triglyceride–glucose (TyG) index is significantly associated with the presence of nonalcoholic fatty liver disease (NAFLD). Alanine aminotransferase (ALT) has been commonly used to screen for NAFLD. Ultrasound fatty liver indicator (US-FLI) is proposed as a non-invasive, semi-quantitative method for predicting NAFLD and accurately identifies histological severity. Objects: We hypothesized that the combination of TyG and ALT would increase the sensitivity and specificity in determining the severity of NAFLD. We evaluated the usefulness of a newly proposed TyG-ALT index for differentiating NAFLD severity and compared it with TyG index. Methods: ALT was used as the screening method for NAFLD (>26 IU/L in boys and >22 IU/L in girls), and the US-FLI was performed on children who met these criteria. US-FLI is a new scoring system ranging 2-8 based on the intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall, difficult visualization of the diaphragm and areas of focal sparing. NAFLD is diagnosed by the minimum score ≥2. The TyG index and the TyG–ALT index were calculated as follows: TyG index=ln(fasting TG [mg/dL]×fasting glucose [mg/dL]/2) and TyG–ALT index= ln(fasting triglyceride [mg/dL]×fasting glucose [mg/dL]×ALT [IU/L]/2). Healthy children of normal weight (body mass index 5-85th percentile) without metabolic comorbidities and no steatosis on ultrasound participated as a control group. Results: A total of 130 NAFLD patients (90 boys and 40 girls) included in this study, with mean age of 11.5±2.29 years. The control group consisted of a total of 28 subjects (17 boys and 11 girls) with mean age of 8.39±1.60 years. Multiple linear regression analysis showed that TyG-ALT index were significantly associated with US-FLI (β=0.356, p<0.001) after controlling for sex, age, and BMI. TyG-ALT index was independent risk factor for NAFLD (odds ratio: 4.218, 95% confidence interval: 1.366-13.020) after controlling for sex, age, and BMI. In the receiver operating characteristic analysis, the area under the curve (AUC) of TyG index was 0.681(p<0.001), 0.681(p<0.001), and 0.782(p<0.001), and AUC of TyG-ALT index was 0.797, (p<0.001), 0.797(p<0.001), and 0.813(p<0.001) in US-FLI ≥4, ≥5, and ≥6, respectively. Conclusions: The TyG–ALT index showed consistently superior detection ability than the TyG index at all severity levels of NAFLD. Further studies are needed to determine its potential role as a noninvasive method for NAFLD screening. Presentation: Thursday, June 15, 2023