Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT), but the clinical utility of ALT in detecting and following individuals with NAFLD remains unclear. We conducted a retrospective analysis of 30,988 men and 5204 women with NAFLD diagnosed by ultrasound and stratified them according to sex-specific ALT quartiles. We compared metabolic variables at baseline and repeated ultrasound after at least 6 months among ALT quartiles (Q) in men (Q1 5–24, Q2 25–33, Q3 34–48, Q4 ≥ 49 IU/L) and women (Q1 5–14, Q2 15–20, Q3 21–28, Q4 ≥ 29 IU/L). Prevalence of obesity (BMI ≥ 25 kg/m2) and metabolic abnormalities (glucose intolerance, hypertension) significantly (p < 0.001) increased from ALT Q1 to Q4 in both men and women at baseline. After a mean follow-up of 4.93 years, 17.6% of men and 31.1% of women resolved their NAFLD. The odds ratio (OR) of resolving significantly (p < 0.001) decreased by quartiles even after multiple adjustments. The adjusted OR for resolution in Q4 was 0.20 (0.18–0.23) in men and 0.35 (0.26–0.47) in women compared with Q1. Individuals with NAFLD span the full range of ALT concentrations, but those with the highest ALT have the worst metabolic profile and persistent NAFLD.
Highlights
Alanine aminotransferase (ALT) is the most widely used biomarker to detect liver disease in clinical practice
One reason for this variability may relate to the reference population used to set the upper limit of normal (ULN) and the inadvertent inclusion of people with nonalcoholic fatty liver disease (NAFLD) [2]
ALT is an important biomarker for fatty liver disease but care needs to be taken in defining the ULN
Summary
Alanine aminotransferase (ALT) is the most widely used biomarker to detect liver disease in clinical practice. The upper limit of normal (ULN) of ALT varies by laboratories and can range widely from 31 to 72 IU/L [1]. One reason for this variability may relate to the reference population used to set the ULN and the inadvertent inclusion of people with nonalcoholic fatty liver disease (NAFLD) [2]. While better delineating ULN, there have been concerns that lowering the ULN would increase the proportion with ALT elevation and increase unnecessary medical evaluation and cost [6]. Applying these ULN to a National Health and Nutrition Examination Survey cohort would classify 36% of U.S adults as having abnormal ALT [7]
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