Metabolic and liver enzyme correlates of serum alpha-fetoprotein in a large health check-up population.

OBJECTIVES: To investigate the associations of metabolic-liver enzyme phenotypes with serum alpha-fetoprotein (AFP) concentrations and to evaluate the individual and joint associations of key metabolic and liver enzyme indicators with AFP. METHODS: This cross-sectional study included 417,535 adults undergoing routine health examinations at the Health Management Center of the First Affiliated Hospital of Wannan Medical College between 2017 and 2023. Participants were classified into four metabolic-liver enzyme phenotypes: metabolically healthy with normal liver enzymes (MHNE), metabolically unhealthy with normal liver enzymes (MUNE), metabolically healthy with elevated liver enzymes (MHEE), and metabolically unhealthy with elevated liver enzymes (MUEE). Associations between AFP and metabolic-liver abnormalities were assessed using multivariable regression models and interaction analyses. RESULTS: AFP concentrations differed significantly across phenotypes and were highest in the MUEE group, whereas the highest odds of elevated AFP were observed in the MHEE group. Compared with the MHNE group, adjusted serum AFP concentrations were 10.1% higher in the MHEE group (β = 0.096) and 12.2% higher in the MUEE group (β = 0.115). Among individual indicators, gamma-glutamyl transferase (GGT) and triglycerides (TG) showed relatively strong positive associations with AFP. For each 1 mmol/L increase in TG, AFP concentrations were 6.6%, 2.2%, and 1.4% higher across the lowest, middle, and highest GGT tertiles, respectively. CONCLUSIONS: Metabolic-liver enzyme phenotypes were associated with modest AFP variation. Elevated liver enzymes were more strongly associated with AFP than metabolic abnormalities alone, while the TG-AFP association weakened across increasing GGT tertiles.