The American journal of medicine · 2026
Normal Alanine Aminotransferase Levels Underestimate the Burden of Steatotic Liver Disease and Fibrosis in US Adults.
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Allam Jad, Nietert Paul, Rockey Don C
Аннотация
BACKGROUND: Despite wide use of serum alanine aminotransferase (ALT) in screening and evaluating liver disease, the definition of a normal ALT is controversial. Here, we aimed to determine the prevalence of steatotic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), and hepatic fibrosis across normal ALT ranges.
METHODS: We performed a cross-sectional study using the National Health and Nutrition Examination Survey. Adults were stratified based on ALT levels of ≤10, 11-20, 21-30, 31-40, 41-80, and >80 U/L. Vibration-controlled transient elastography was used to assess hepatic steatosis (controlled attenuation parameter of ≥ 285 dB/m), and clinically significant and advanced fibrosis (> 8.6 kPa and 13.1 kPa, respectively). Outcomes included the prevalence of steatotic liver disease, MASLD, MetALD, and hepatic fibrosis across ALT strata. Multivariable logistic regression examined the association between normal ALT strata and each outcome.
RESULTS: In 5,245 adults, steatotic liver disease prevalence increased stepwise from 17% at ALT ≤10 U/L to 26% at ALT 11-20 U/L, 44% at 21-30 U/L, and 52% at 31-40 U/L (p<0.001). MASLD and MetALD followed similar graded patterns (both p<0.001). Relative to a reference ALT 11-20 U/L, ALT 21-30 U/L was independently associated with significantly greater odds of steatotic liver disease (aOR, 1.80 [95% CI, 1.26-2.58]), MASLD (aOR, 1.57 [1.18-2.09]), MetALD (aOR, 1.82 [1.41-2.34]), clinically significant fibrosis (aOR, 1.64 [1.12-2.40]), and advanced fibrosis (aOR, 1.94 [1.30-2.89]).
CONCLUSION: A significant burden of steatotic liver disease, MASLD, MetALD, and hepatic fibrosis exists at ALT values commonly considered normal, suggesting current reference ranges may be too high to reliably exclude liver disease.
METHODS: We performed a cross-sectional study using the National Health and Nutrition Examination Survey. Adults were stratified based on ALT levels of ≤10, 11-20, 21-30, 31-40, 41-80, and >80 U/L. Vibration-controlled transient elastography was used to assess hepatic steatosis (controlled attenuation parameter of ≥ 285 dB/m), and clinically significant and advanced fibrosis (> 8.6 kPa and 13.1 kPa, respectively). Outcomes included the prevalence of steatotic liver disease, MASLD, MetALD, and hepatic fibrosis across ALT strata. Multivariable logistic regression examined the association between normal ALT strata and each outcome.
RESULTS: In 5,245 adults, steatotic liver disease prevalence increased stepwise from 17% at ALT ≤10 U/L to 26% at ALT 11-20 U/L, 44% at 21-30 U/L, and 52% at 31-40 U/L (p<0.001). MASLD and MetALD followed similar graded patterns (both p<0.001). Relative to a reference ALT 11-20 U/L, ALT 21-30 U/L was independently associated with significantly greater odds of steatotic liver disease (aOR, 1.80 [95% CI, 1.26-2.58]), MASLD (aOR, 1.57 [1.18-2.09]), MetALD (aOR, 1.82 [1.41-2.34]), clinically significant fibrosis (aOR, 1.64 [1.12-2.40]), and advanced fibrosis (aOR, 1.94 [1.30-2.89]).
CONCLUSION: A significant burden of steatotic liver disease, MASLD, MetALD, and hepatic fibrosis exists at ALT values commonly considered normal, suggesting current reference ranges may be too high to reliably exclude liver disease.