Fibrosis and steatotic liver disease in US adolescents according to the new nomenclature

Abstract

Objective: To apply the new nomenclature for steatotic liver diseases (SLD), replacing nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD), in adolescents using National Health and Nutrition Examination Survey (NHANES) data.

Methods: Among 1410 adolescents (12-19 years) in NHANES (2017-March, 2020), the controlled attenuation parameter (CAP) of transient elastography (TE) was used to define steatosis and fibrosis (TE ≥ 7.4 kPa). Obesity and alanine aminotransferase (ALT) ≥ 80 U/L were used to identify adolescents qualifying for hepatology referral according to practice guidelines. NAFLD was defined as liver steatosis without a specific exposure; it has no cardiometabolic risk factor requirement, unlike MASLD.

Results: Steatosis (yes/no) is the first decision point in the new diagnostic protocol; however, criteria for steatosis are undefined. At the supplier (EchoSens)-recommended CAP threshold of 240 dB/m, 30.5% (95% confidence interval [CI]: 27.1%-34.0%) of adolescents had SLD and about 85% of adolescents with NAFLD met criteria for MASLD. The other 15% would receive an ambiguous diagnosis of either cryptogenic SLD or possible MASLD. At higher CAP thresholds, MASLD/NAFLD concordance increased and approached 100%. Among adolescents with MASLD-fibrosis, only 8.8% (95% CI: 0%-19.3%) had overweight/obese and ALT ≥ 80 U/L.

Conclusions: The new nomenclature highlights the high prevalence of liver steatosis. At the CAP threshold of 240 dB/m, however, approximately 15% of adolescents would receive an ambiguous diagnosis, which could lead to confusion and worry. Fewer than 10% of adolescents with MASLD-fibrosis had overweight/obese and ALT ≥ 80 U/L. Revised guidelines are needed to ensure that the other 90% receive appropriate referral and liver disease care.

Keywords: MASLD; NHANES; VCTE; cardiometabolic risk factors; cryptogenic SLD.

FIGURE 1

The new nomenclature’s diagnostic scheme applied to adolescents in the United States. The flowcharts show 1410 adolescents (age 12–19 years old) categorized (A) according to new nomenclature; and (B) according to NAFLD criteria. The graph shows MASLD/NAFLD concordance with different CAP thresholds of steatotic liver disease. CAP, controlled attenuation parameter; MASLD, Metabolic dysfunction-associated steatotic liver disease; MetALD, Metabolic dysfunction-associated alcohol-associated liver disease; NAFLD, nonalcoholic fatty liver disease; NHANES, National Health and Nutrition Evaluation Survey.

FIGURE 2

The age-standardized-weighted percentage of SLD using different VCTE-CAP thresholds to define SLD, with stratification by race/ethnicity. The age-standardized-weighted prevalence of SLD based on different thresholds of VCTE-CAP were determined for the total cohort (black), non-Hispanic White (NHW, blue), non-Hispanic Black (NHB, red), Mexican American (MA, gray) and other (O, light gray) racial/ethnic groups. Differences between groups were tested by univariate t statistic. Statistical significance was a two-sided p < 0.05. *p < 0.05, **p < 0.001. CAP, controlled attenuation parameter; SE, standard error; SLD, steatotic liver diseases; VCTE, vibration controlled transient elastography.