Kariv R et al. (2006) Re-evaluation of serum alanine aminotransferase upper normal limit and its modulating factors in a large-scale population study. Liver Int 26: 445–450

It has recently been proposed that the true upper normal limit of serum alanine aminotransferase (ALT) is much lower than that listed by the manufacturers of commercially available assays. The normal ranges for laboratory parameters such as serum ALT are often derived from the assessment of only a few hundred participants. This assessment usually consists of questionnaires and a very limited laboratory work-up, and the participants might not necessarily be truly representative of a 'healthy' population. Furthermore, modulating factors are often not taken into account when determining normal ranges.

Kariv et al. reviewed the ALT test results of 17,496 patients from an Israeli health organization's database, in order to assess the true upper normal limit of serum ALT. None of these patients had abnormal laboratory findings, diagnoses that could affect liver test results, or were taking potentially hepatotoxic medication. After stratifying the cohort for age and sex, they found an upper normal limit of 37.5 U/l, which is significantly lower than the limit of 52 U/l that was listed by the manufacturers of the test used (P <0.0001).

A possible limitation of this study is that BMI data were not available—it is possible that the true upper limit is even lower than found here, as patients with a high BMI could not be excluded. The authors suggest that lowering the upper normal limit for serum ALT might increase test sensitivity, but at the possible cost of decreased specificity. Until a decision has been made, they recommend that clinicians should treat patients with serum ALT levels close to the upper limit with caution, as even these 'normal' levels might indicate significant liver pathology.