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SYDNEY, Australia, Dec. 5 -- The upper limit of normal for alanine aminotransferase (ALT) in adolescent males has been too high, said researchers here.

The upper limit was calculated at 28 IU/L in 439 males 12 to 19 years old, considerably lower than standard definitions, which are in the 45 to 55 IU/L range, Jacob George, Ph.D., of the University of Sydney, and colleagues, reported in the December issue of Hepatology.

The new upper limit is the 95th percentile for ALT levels in adolescents at the lowest risk for liver disease.

The group found that 17% of those in the overall group, all juvenile offenders, had above-normal ALT.

Strong associations with elevated ALT included HCV antibody positivity, overweight and obesity, and elevated total cholesterol, they found. More than 90% of adolescents with elevated ALT levels had one or more features of the metabolic syndrome.

"There was a strong association for overweight or obesity (72% versus 25.1%; P<0.001) to predict elevated ALT," they wrote. Multivariate analysis for these factors indicated an odds ratio of 6.9 for elevated ALT with overweight or obesity (95% CI: 3.7 to 13.1, P<0.001).

"This definition will permit greater sensitivity in diagnosing early liver injury in adolescent male populations," they wrote. "By identifying those with [hepatitis B and C infection] and obesity-related liver disease, targeted interventions can and should be implemented to minimize future health-related morbidity."

The researchers also identified new upper limits of normal in male adolescents for two other liver enzymes: 32 IU/L for aspartate aminotransferase (AST), and 29 IU/L for gamma-glutamyltranspeptidase (GGT). Published values for the upper normal limits in adults range up to 42 IU/L for AST and 48 IU/L for GGT.

The 439 adolescents in the New South Wales criminal justice system agreed to participate and did not have serious mental problems or substance withdrawal or disruptive behavior when blood samples were drawn. In addition to liver enzymes, the samples were tested for blood lipids, glucose, and hepatitis B and C antibodies and viral loads.

As expected, participants with HCV infection were at significant risk for elevated ALT relative to HCV-negative participants (57.1% versus 16.3%, P<0.001). This translated into an odds ratio of 14.6 (95% CI: 3.7 to 57.6) for elevated ALT in HCV-positive participants.

When 81 of the participants gave additional blood samples one year later, about 3.7% of those who were initially HCV-negative tested positive.

"Greater education regarding blood-borne viruses, risk factors for transmission, and implementing harm minimization strategies in this population is crucial," the researchers said.

They also recommended routine hepatitis B vaccination for adolescent offenders, noting that only 30% of the participants showed immunity to HBV. Risk-taking sexual activity and drug-taking behaviors put this population at high risk for HBV infection, they said, though only 4% of participants were HBV positive.

High levels of cholesterol were also significantly associated with above-normal ALT (odds ratio: 3.6, 95% CI: 1.7 to 7.7).

The study was funded by the Australian Research Council, the University of Sydney and industry partners, and the New South Wales Department of Juvenile Justice and Justice Health. No financial disclosures were reported.

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