Upper limits of normal for alanine aminotransferase activity in the United States population


  • Constance E. Ruhl,

    Corresponding author
    1. Social and Scientific Systems, Inc., Silver Spring, MD
    • Social and Scientific Systems, Inc., 8757 Georgia Avenue, 12th Floor, Silver Spring, MD 20910
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    • fax: 301-628-3201

  • James E. Everhart

    1. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD
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  • Potential conflict of interest: Nothing to report.


Alanine aminotransferase (ALT) is an important test for liver disease, yet there is no generally accepted upper limit of normal (ULN) in the United States. Furthermore, the ability of ALT to differentiate persons with and without liver disease is uncertain. We examined cut-offs for ALT for their ability to discriminate between persons with positive hepatitis C virus (HCV) RNA and those at low risk for liver injury in the U.S. population. Among adult participants in the 1999-2008 U.S. National Health and Nutrition Examination Survey, 259 were positive for serum HCV RNA and 3,747 were at low risk for liver injury (i.e., negative HCV RNA and hepatitis B surface antigen, low alcohol consumption, no evidence of diabetes, and normal body mass index and waist circumference). Serum ALT activity was measured centrally. Maximum correct classification was achieved at ALT = 29 IU/L for men (88% sensitivity, 83% specificity) and 22 IU/L (89% sensitivity, 82% specificity) for women. The cut-off for 95% sensitivity was an ALT = 24 IU/L (70% specificity) for men and 18 IU/L (63% specificity) for women. The cut-off for 95% specificity was ALT = 44 IU/L (64% sensitivity) for men and 32 IU/L (59% sensitivity) for women. The area under the curve was 0.929 for men and 0.915 for women. If the cut-offs with the best correct classification were applied to the entire population, 36.4% of men and 28.3% of women would have had abnormal ALT. Conclusion: ALT discriminates persons infected with HCV from those at low risk of liver disease, but would be considered elevated in a large proportion of the U.S. population. (HEPATOLOGY 2012)