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


OBJECTIVE
To estimate the ULN for serum ALT and to identify factors modulating it.


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 laboratory 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/l, respectively. 6.2% (16 943/273 273) of subjects whose ALT was below ULN listed by the test manufacturer (52 U/l), 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.
Kariv
Revital
R
Department of Gastroenterology and Liver Disease, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
Leshno
Moshe
M
Beth-Or
Anat
A
Strul
Hana
H
Blendis
Laurie
L
Kokia
Ehud
E
Noff
Dina
D
Zelber-Sagie
Shira
S
Sheinberg
Bracha
B
Oren
Ran
R
Halpern
Zamir
Z
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008107:Liver Diseases / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009765:Obesity; D012016:Reference Values; D012044:Regression Analysis; D012189:Retrospective Studies; D012737:Sex Factors
D001786:Blood Glucose; D008055:Lipids; D000410:Alanine Transaminase