Subjects with sonographical hepatic steatosis should be excluded from studies to establish upper reference levels of serum transaminases

Background and aims: Correct upper reference limits (URL) of serum liver enzyme activities are used to select individuals in whom further diagnostic procedures for suspected liver disorders are warranted and to compare the prevalence and incidence of increased serum liver enzyme levels within and among populations. We sought to establish URL in a general adult population by not only generating a disease‐free population but also further excluding subjects with ultrasonographical diagnosis of hepatic steatosis. Methods: We used data from 4242 subjects (2154 women) aged 20–79 years recruited for the population‐based Study of Health in Pomerania. A reference population was selected comprising 1953 subjects (1129 women). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ‐glutamyltransferase (GGT) were measured photometrically. Results: The exclusion of 630 subjects with hepatic steatosis and 20 subjects with equivocal data on liver ultrasound from the reference population predominantly affected the URL for serum ALT and GGT levels in younger age groups. URL for serum ALT, AST and GGT levels were 1.00 μmol/L/s (60 U/L), 0.55 μmol/L/s (33 U/L) and 1.11 μmol/L/s (67 U/L), respectively, in men as well as 0.57 μmol/L/s (34 U/L), μmol/L/s (25 U/L) and μmol/L/s (39 U/L), respectively, in women. Conclusions: URL for serum liver enzyme activities are higher than recommended previously. Creating a reference population for establishing URL for serum liver enzyme activities should include liver ultrasound in order to exclude subjects with subclinical hepatic steatosis.