Shifting alanine aminotransferase distribution among US adults, the National Health and Nutrition Examination Survey 1988-2020.

Background: The dynamics of alanine aminotransferase (ALT) remain poorly described in the general population owing to the unavailability of widely accepted cutoffs to define abnormal levels and insensitivity of dichotomized ALT values.

Methods: With data from the National Health and Nutrition Examination Survey 1988-1994 (n = 11 854), 1999-2004 (12 280), 2005-2010 (14 204), 2011-2016 (14 145), and 2017-2020 (7047), we examined the age- and sex-standardized distribution of log-transformed serum ALT and tested the elevated ALT prevalence trend among American adults aged 19 years and older.

Results: The ALT geometric mean increased from 15.89 U/L (95% confidence interval = 15.43-16.37) in 1988-1994 to 21.97 U/L (21.75-22.20) in 1999-2004. The means remained around 22 U/L between 2004 and 2016 and then decreased to 19.19 U/L (18.85-19.54) in 2017-2020 (P for quadratic trends <0.001). However, the 95th percentile of the bell-distribution remained around 49 U/L by the end of the study after jumping from 38.39 U/L (35.73-41.06) in 1988-1994 to 48.86 U/L (47.34-50.39) in 1999-2004. Correspondingly, the elevated ALT prevalence doubled from 1988-1994 to 1999-2004 and remained unchanged through 2020, independent of the cutoffs used.

Conclusions: The ALT mean level decreased in recent years, but the right end of the bell-shaped distribution was stagnant, and the elevated ALT prevalence levels remained persistently high. The reductions in ALT levels likely corresponded to population-wide reductions in fructose consumption. The prevalent elevated ALT requires effective clinical interventions.