Abstract
BackgroundThe 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 exhibit various metabolic changes during the follow-up period in patients with NAFLD.MethodsWe performed 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. All patients received recommendations for lifestyle modifications and guideline-recommended pharmacological treatments with indications for drug therapy for metabolic abnormalities.ResultsOverall, 1048 patients with NAFLD were included and received lifestyle modification recommendations and pharmaceutical interventions, including 637 (60.7%) patients with abnormal GGT levels and 767 (73.2%) patients with abnormal ALT levels. Patients with concurrent ALT and GGT abnormalities presented higher levels of metabolism indexes and higher liver fat content than those in patients with single or no abnormalities. After 12 months of follow-up, the cumulative normalization rate of GGT was considerably lower than that of ALT (38% vs. 62%, P < 0.001). Greater weight loss resulted in higher cumulative normalization rates of GGT and ALT. Weight loss (OR = 1.21, 95% CI 1.11–1.32, P < 0.001), ALT normalization (OR = 2.75, 95% CI 1.41–5.36, P = 0.01) and lower TG and HOMA-IR values (OR = 2.03, 95% CI 1.11–3.71, P = 0.02; OR = 2.04, 95% CI 1.07–3.89, P = 0.03) were independent protective factors for GGT normalization. Elevated baseline GGT (OR = 0.99, 95% CI 0.98–0.99, P = 0.01) was a risk factor.ConclusionsFor 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 a reliable predictor of GGT normalization.
Highlights
The normalization of liver biochemical parameters usually reflects the histological response to treat‐ ment for nonalcoholic fatty liver disease (NAFLD)
A total of 1048 patients with NAFLD were included in this study and were divided into 4 groups based on the normalization of baseline Alanine aminotransferase (ALT) and/or Gamma-glutamyl transferase (GGT) levels after follow-up: a both ALT and GGT abnormal group (n = 486), an ALT-only abnormal group (n = 281), a GGT-only abnormal group (n = 151), and a both ALT and GGT normal group (n = 130) (Fig. 1)
Compared with the other three groups, significant increases in uric acid levels, fasting insulin levels, and homeostatic model assessment of insulin resistance (HOMA-insulin resistance (IR)) levels but not blood lipid metabolism were observed in the group with abnormal levels of both ALT and GGT
Summary
The normalization of liver biochemical parameters usually reflects the histological response to treat‐ ment for nonalcoholic fatty liver disease (NAFLD). Based on data from emerging studies, both elevated baseline serum ALT and GGT levels are significantly associated with insulin resistance, other metabolic syndromes and an increased risk of long-term complications of myocardial infarction and stroke [9, 10]. The relationship between the dynamic changes in GGT and ALT levels and their metabolic treatment responses during the treatment of patients with NAFLD remains to be elucidated [7]. This issue is of particular clinical importance, as these biochemical markers of hepatitis remission may exhibit inconsistent levels during therapy— namely, the levels of one of the markers can decrease to its normal range while the levels of other markers remain abnormal. Relevant studies may be helpful to interpret the results of biochemical assessments conducted during the disease course [6, 7]
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