Updated definitions of healthy ranges for serum alanine aminotransferase levels.
Level 3 - non-randomized controlled study
Retrospective cohort study evaluating diagnostic thresholds and reference ranges
PubMed 12093239 · doi:10.7326/0003-4819-137-1-200207020-00006
What was done
This retrospective cohort study at a university hospital in Milan, Italy, analyzed 6835 first-time blood donors without contraindications or anti-hepatitis C virus (HCV) antibodies from 1995 through 1999, along with 209 individuals who attempted blood donation between 1990 and 1999 and had anti-HCV antibodies (131 with HCV viremia, 133 with liver biopsy). Univariate and multivariate analyses evaluated associations between clinical and laboratory factors and ALT levels. Healthy ALT reference ranges were calculated from participants at lowest risk for liver disease, and their sensitivity and specificity were compared to standard limits in donors with HCV antibodies.
What was found
Serum ALT activity was independently associated with body mass index and laboratory markers of abnormal lipid or carbohydrate metabolism. Calculated upper limits for healthy ALT were 30 U/L (500 nkat/L) in men and 19 U/L (317 nkat/L) in women, compared with conventional limits of 40 U/L (667 nkat/L) in men and 30 U/L (500 nkat/L) in women. During 6-month follow-up, the updated limits showed higher sensitivity for detecting HCV viremia than conventional limits (76.3% [95% CI, 69.1% to 83.6%] versus 55% [CI, 46.4% to 63.5%]) with specificity of 88.5% [CI, 79.2% to 94.6%] versus 97.4% [CI, 91% to 99.7%]. The increased sensitivity primarily identified individuals with minimal to mild histologic liver lesions.
Why it matters
Standard ALT cutoffs established on populations with subclinical liver disease miss individuals with mild hepatic injury. Lowering normal ALT thresholds improves identification of patients with chronic HCV infection and nonalcoholic fatty liver disease.
Limits
The study design was retrospective and conducted at a single center in Italy among blood donors, who are subject to donor selection bias and may not reflect the general population. Liver histology was only assessed in a subset of HCV-positive individuals rather than the reference cohort.
Cited by
- context The reference range upper limit for alanine aminotransferase (ALT) in standard laboratory testing has shifted from 25 U/L in the 1970s up to 40 U/L today.