Abstract
Nonalcoholic fatty liver disease (NAFLD) represents a chronic hepatic disorder marked by excessive lipid deposition within liver tissues. Previous studies have identified the gamma-glutamyl transferase to high-density lipoprotein cholesterol (GGT/HDL-c) ratio as a potential marker associated with NAFLD risk. However, the influence of triglyceride (TG) levels on this association has not been fully elucidated. This study was designed to assess whether TG modulates the relationship between GGT/HDL-c and the incidence of NAFLD, and to explore the possible interaction between TG and GGT/HDL-c in relation to NAFLD risk. This investigation was a secondary analysis based on data from a cohort study, encompassing 11,692 nonobese Chinese adults. Participants were stratified into 2 groups according to their triglyceride levels: hypertriglyceridemia (TG ≥ 1.7 mmol/L) and non-hypertriglyceridemia (TG < 1.7 mmol/L). Additionally, the GGT/HDL-c ratio was divided into quartiles for detailed analysis. The association between GGT/HDL-c, TG, and the occurrence of NAFLD was evaluated using Cox proportional hazards regression models. Furthermore, the potential modifying effect of TG on the GGT/HDL-c-NAFLD relationship was examined by categorizing participants into 8 subgroups based on TG status and quartiles of GGT/HDL-c ratio. During a mean follow-up duration of 29.24 months, 1926 individuals (16.47%) were newly diagnosed with NAFLD. Both elevated GGT/HDL-c ratios and higher TG concentrations were significantly correlated with an increased risk of developing NAFLD. TG levels influenced the strength of the association between GGT/HDL-c and NAFLD. Specifically, the association was stronger among individuals without hypertriglyceridemia (HR = 1.019, 95% CI = 1.015-1.023, P < .0001), and comparatively weaker in the hypertriglyceridemia group (HR = 1.012, 95% CI = 1.008-1.016, P < .0001). Moreover, a significant interaction effect was observed between TG and GGT/HDL-c, with the greatest risk identified in participants exhibiting both elevated GGT/HDL-c ratios and high TG levels (HR = 6.662, 95% CI = 5.237-8.474, P < .0001). Triglyceride levels appear to modify the relationship between GGT/HDL-c and NAFLD risk, with a notable interaction effect between these 2 factors. Among nonobese Chinese adults, simultaneous management aimed at reducing both GGT/HDL-c ratios and TG concentrations may contribute to lowering the risk of NAFLD onset.