Serum alanine aminotransferase (ALT) levels have been used to evaluate liver disease, but they may fail to identify patents with chronic hepatitis C virus (HCV) who have low levels of liver inflammation. Presently, the normal range for ALT is identified as 40 U per L, with a range from 30 to 50 U per L. The populations used to determine this normal level in the 1980s probably included patients with nonal-coholic fatty liver, which is now acknowledged to be a common cause of chronic liver disease. The prevalence of chronic liver disease may be underestimated if this normal range is used. Prati and associates used the results of a four-year study of first-time blood donors to update the acceptable ALT range and identify a healthy range.

This newly identified range was then tested for sensitivity and specificity among anti-HCV–positive persons with and without documented liver disease. More than 6,000 healthy blood donors and 209 persons with confirmed anti-HCV were included. The median ALT level in the entire group was 12 U per L, with men having a slightly higher range than women. The sex-specific 95th percentile for ALT among the healthy blood donors was 30 U per L in men and 19 U per L in women, and these were suggested as healthy ALT levels.

When the old normal ALT range was compared with the new healthy range to detect ALT abnormalities among anti-HCV–positive persons, the sensitivity for liver disease of the new range's gender-specific levels was significantly higher, while the specificity was slightly lower. Persons with a greater body mass index (BMI), glucose intolerance, or hyperlipidemia tended to have higher ALT levels.

The authors conclude that updated normal or healthy guidelines would better identify persons at risk for liver disease. These patients should probably be investigated for liver disease. Flexibility is appropriate considering the impact of other factors that may cause slight elevations of ALT, including obesity and hyperlipidemia.

In an editorial in the same journal, Kaplan legitimizes the findings of this study but puzzles over the implications. He discusses three courses of action: accepting the new lower ALT range, adjusting the current ALT range for effects of BMI and sex, and leaving the current standards alone. He suggests that combining the last two options would be appropriate because adapting the new ALT range would greatly increase the number of persons with ALT elevations who would require evaluation and impose anxiety on many otherwise healthy persons. Although additional patients with chronic HCV infection might be discovered, these patients with minimally elevated ALT levels generally have a more benign disease course that has not been documented to improve with treatment.