Normalization of γ-glutamyl Transferase Levels is Associated with Better Metabolic Control in Individuals with Nonalcoholic Fatty Liver Disease

Abstract

Background: The normalization of liver biochemical parameters usually reflects the histological response to treatment for nonalcoholic fatty liver disease (NAFLD). Researchers have not clearly determined whether different liver enzymes exhibited various metabolic changes during the follow-up of patients with NAFLD.Methods: We conducted a retrospective analysis of patients with NAFLD who were receiving therapy from January 2011 to December 2019. Metabolism indexes, including glucose levels, lipid profiles, uric acid levels and liver biochemical parameters, were measured. Magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) and liver ultrasound were used to evaluate steatosis.Results: Overall, 1048 patients with NAFLD were included and received lifestyle and pharmaceutical interventions, including 637 (60.7%) patients with abnormal GGT levels and 467 (44.6%) patients with abnormal ALT levels. Patients with concurrent ALT and GGT abnormalities presented higher levels of metabolism indexes and higher liver fat contents than patients with single or no abnormalities. After 12 months of follow-up, the cumulative normalization rate of GGT was much lower than that of ALT (33% vs. 52%, P < 0.001). Greater weight loss resulted in higher cumulative normalization rates of GGT and ALT. Weight loss (OR = 1.27, 95%CI: 1.15~1.41, P < 0.001), ALT normalization (OR = 4.32, 95%CI: 1.87~9.96, P = 0.01) and HOMA-IR decreased to normal levels (OR = 3.48, 95%CI: 1.60~7.57, P = 0.01) were independent protective factors for GGT normalization. Elevated baseline GGT (OR = 0.99, 95%CI: 0.98~0.99, P = 0.01), CHOL (OR = 0.47, 95%CI: 0.23~0.96, P = 0.04) and fasting insulin levels (OR = 0.91,95%CI: 0.86~0.96, P = 0.01) were risk factors.Conclusions: For NAFLD patients with concurrently increased ALT and GGT levels, a lower normalization rate of GGT was observed rather than ALT. Good control of weight and insulin resistance was reliable predictors of GGT normalization.