Metabolic Health Phenotypes Among Middle- to Older-Aged Adults Living With and Without Obesity: Relationships With Hepatic Health Indicators

Background: The recent reclassification of nonalcoholic fatty liver disease to metabolic dysfunction-associated steatotic liver disease reflects the central role of metabolic dysfunction in its pathogenesis. Obesity underlies metabolic perturbations; however, liver health risks are not exclusive to individuals with a higher BMI and some individuals with obesity have favorable metabolic health (MH). Thus far, there has been limited examination of liver health indicators among metabolically healthy and unhealthy phenotypes, which is the aim of this study. Methods: A cross-sectional sample of 2040 middle- to older-aged adults were classified as metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), metabolically healthy nonobese (MHNO), and metabolically unhealthy nonobese (MUNO), according to three MH definitions (MeigsA, MeigsB, and Wildman). Liver biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were measured, and the fatty liver index (FLI) was calculated. Crude and adjusted logistic regression models examined associations between liver function indicators and MH phenotypes. Results: In fully adjusted models, higher FLI scores were consistently associated with lower likelihood of MHO and MHNO (odds ratios and 95% confidence intervals for MHO: 0.947 (0.934, 0.961) [MeigsA], 0.952 (0.938, 0.966) [MeigsB] and 0.945 (0.931, 0.959) [Wildman] and for MHNO: 0.957 (0.950, 0.964) [MeigsA], 0.950 (0.942, 0.958) [MeigsB] and 0.961 (0.955, 0.968) [Wildman] (all p < 0.001)). Higher ALT and GGT concentrations were inversely associated with MHO, and AST additionally with MHNO, in all models across the three definitions. Conclusions: Liver function indicators are linked with MH status in middle- to older-aged adults. Keywords: fatty liver index; liver health biomarkers; metabolic associated fatty liver disease; metabolic health phenotypes; non‐alcoholic fatty liver disease; obesity.