The Optimal Cut-Points of Alanine Aminotransferase for Screening Metabolic Syndrome in Iranian Adults

Abstract

Background: Studies have reported that the activity of alanine aminotransferase (ALT) is a key biomarker for screening liver cell damage, such as non-alcoholic fatty liver disease (NAFLD). Objectives: Since individuals with metabolic syndrome (MetS) are at high risk for NAFLD, we aimed to determine gender-specific ALT thresholds for screening MetS in the Tehranian population. Methods: We conducted a cross-sectional study from 2018 to 2022, involving 4,968 adults aged 20 - 70 years (2,732 females). Multivariable logistic regression analysis was performed to assess the association between ALT levels and the prevalence of MetS, as well as its individual components. Additionally, gender-specific ALT cut-off points were determined using the maximum Youden's Index. The area under the receiver operating characteristic curve (AUC) was calculated to derive thresholds and compare them with the previously introduced cut-off points for liver-related mortality in the U.S. population (US-LRM) (ALT > 19 U/L for females, > 29 U/L for males). We also examined the diagnostic performance of the derived cut-off points in 11 147 individuals (7,154 women) from the atherosclerosis risk in communities (ARIC) study as an external validation. Results: The odds ratio (OR) from the logistic regression analysis showed that each 5 U/L increase in ALT level was associated with an increased prevalence of MetS [19% for females and 8% for males] and its components (ranging from 7 - 19% in females and 3-10% in males; all P-values < 0.05). The suggested cut-off point for ALT in males was 21 U/L, with a sensitivity of 72.1% and specificity of 47.1%. For females, with a threshold of 18 U/L, the corresponding values were 57.9% sensitivity and 66.5% specificity. Compared to the US-LRM suggested cut-off points in the US population, the AUC of our suggested threshold increased in males (60% vs. 56%, respectively), while for females, it remained the same as in the pretest (≈ 62%). Using ARIC data, our suggested threshold showed nearly identical AUC values to the US-LRM threshold in females (58% vs. 57%, respectively), whereas for males, the highest AUC was observed for our suggested cut-off points (56%), followed by the mortality-related threshold (53%). Conclusions: The cut-off point for screening MetS among Iranian women was almost identical to the lower suggested threshold in American guidelines but was notably lower for defining abnormal ALT levels in males.