Serum Alanine Aminotransferase Upper Normal Limits in Healthy Population: A Systematic Review

BACKGROUND: Measuring serum alanine aminotransferase (ALT) enzyme is a routine clinical test commonly used to evaluate abnormalities in the body in general and liver function in particular. Higher ALT levels are associated with a number of metabolic disorders. The upper limit normal (ULN) is considered as a reliable threshold for definition of high ALT. OBJECTIVES: To assess existing evidence on the ULN for ALT in the general population. DATA SOURCE: PubMed (Medline), EMBASE, Scopus, and Web of Science (ISI) were searched using a specified search strategy. ELIGIBILITY CRITERIA: We collected documents published from 1980 to 2018 in English, focusing on human samples in the population level and extracted the data after qualitative evaluation. METHODS: We conducted this study in accordance with the Preferred Reporting Item for systematic reviews meta-analysis (PRISMA) statement recommendation. We used specific search terms and their combinations to find documents from relevant databases. We used snowballing approach to find documents not captured in the main phase of the search. Two authors separately conducted the search, screened the articles, and selected documents that were qualified for data extraction based on defined inclusion criteria. Finally, data extraction was conducted by two authors using PRISMA checklist. Reported ULNs for ALT and 95% confidence intervals (CIs) were documented in previously developed data sheets. RESULTS: Out of 15242 studies, 47 articles were included for data extraction and analysis. Data was sparse and lacked consistency to precisely estimate ULN for serum ALT. The ULN of ALT was significantly diverse across various geographical locations and sexes. The lowest value of ULN for ALT was 19 IU/L in Chinese children (age range: 7 to <10) and the highest value of ULN for ALT was 55 IU/L in children from Ghana aged < 5 years. LIMITATIONS: The main limitation of the current systematic review was the scarcity of reported measures for ULN of ALT. CONCLUSIONS: Based on the results of the current systematic review, it is suggested that the normal range of ALT be redefined, but this redefinition should be done according to the localized data. In order to redefine the ULN for ALT, regional differences, methods used in ALT measurements, and ULN determination should be considered.