Re-evaluation of serum alanine aminotransferase upper normal limit and its modulating factors in a large-scale population study

Revital Kariv, Moshe Leshno, Anat Beth-Or, Hana Strul, Laurie Blendis, Ehud Kokia, Dina Noff, Shira Zelber-Sagie, Bracha Sheinberg, Ran Oren, Zamir Halpern

Research output: Contribution to journalArticlepeer-review


Background: The upper normal limit (ULN) of serum alanine-aminotrasferase (ALT) normal range was recently challenged, because patients diagnosed with liver diseases may have 'normal' or near-'normal' ALT levels, and because possible modulators are often ignored in determining normal range. Aim: To estimate the ULN for serum ALT and to identify factors modulating it. Subjects and methods: We reviewed medical records of subjects aged 15-90, who underwent standard panels of laboratory tests, including serum ALT, over 6 months at a central laboratory. Three groups were defined: Group 1, comprised total study population (N = 272 273). Group 2 (N = 87 020) comprised total study population, excluding those receiving potentially hepatotoxic drugs, or diagnosed with liver disease, or had any abnormal test results other than for triglycerides, cholesterol, glucose, or HbA1c. Group 3 (N = 17 496) the 'healthy' population, from whose ALT values we established the new ULN, comprised Group 2 subjects with normal triglycerides, cholesterol, glucose, and HbA1c levels. Results: The 95th percentile ALT values, corresponding to the ULN, in groups 1, 2, and 3 were 50.1, 40, and 37.5 U/1, respectively. 6.2% (16 943/273 273) of subjects whose ALT was below ULN listed by the test manufacturer (52 U/1), had ALT level above our new ULN. Linear and logistic-regression analyses showed that ALT levels were significantly modified by gender, age, glucose, cholesterol, triglycerides, and overweight/obesity diagnosis. Significant interaction was found between gender, glucose and cholesterol levels. Conclusions: In this first large-scale study of 'healthy' population, serum ALT ULN was far lower than currently accepted value. Age and gender may be considered when determining the ULN for ALT.

Original languageEnglish
Pages (from-to)445-450
Number of pages6
JournalLiver International
Issue number4
StatePublished - May 2006
Externally publishedYes


  • Alanine transaminase
  • Liver disease
  • Normal range
  • Normal values
  • Reference values

ASJC Scopus subject areas

  • Hepatology


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