Determining Upper Limit of Alanine Aminotransferase in Iranian Cohort Population Using Ultrasound Screening for Liver Diseases

Background: Alanine aminotransferase (ALT) has a variable normal range according to race and ethnicity. So, the upper normal level of ALT localized for the Iranian population was determined in the Ravansar Non-Communicable Disease (RaNCD) cohort population by re-evaluation of high-risk people. Methods: A cohort population with normal ALT results based on the current kit was checked for a history of liver diseases. After excluding them, the remaining population was included in the distribution diagram of individuals with apparently healthy livers. Participants whose ALT values were in the 90th to 100th percentile were re-evaluated by ultrasonography (US) and a checklist of liver disease. Patients identified as having liver disease or those with other abnormal liver enzymes were excluded, and the 95th percentile was extracted from the distribution diagram of the remaining population. Results: After excluding liver disease, among 8046 participants of RaNCD, US and re-evaluation were performed in 543 high-risk individuals. Liver disease was diagnosed in 74.6% by US. The most common liver disease was metabolic dysfunction-associated steatotic liver disease (MASLD), accounting for 69.7%. Grade 2 or 3 of MASLD was found in 23.2%. After excluding patients with abnormal liver enzymes and liver disease, the 95th percentile of ALT was 29 U/L in women (sensitivity: 53%, specificity: 82%) and 36 U/L in men (sensitivity: 28%, specificity: 90%). Conclusion: The calculated 95th percentile was lower than the routine cut-off value of the current kit in both sexes. Generalizability is a significant advantage of our results, provided by the lack of exclusion of patients with metabolic risk factors and the use of US to exclude MASLD.