Non-Alcoholic Fatty Liver Disease Modifies Serum Gamma-Glutamyl Transferase in Cigarette Smokers

Background: Serum gamma-glutamyl transferase (GGT) is a marker of oxidative stress, associated with increased cardiovascular (CV) risk. The impact of smoking on oxidative stress may be aggravated in individuals with non-alcoholic fatty liver disease (NAFLD). We aimed to ascertain the association of smoking on GGT levels in the presence or absence of NAFLD. Methods: We evaluated 6,354 healthy subjects (43 ± 10 years, 79% males) without clinical cardiovascular disease (CVD) undergoing an employer-sponsored physical between December 2008 and December 2010. NAFLD was diagnosed by ultrasound and participants were categorized as current or non-smokers by self report. A multivariate linear regression of the cross-sectional association between smoking and GGT was conducted based on NAFLD status. Results: The prevalence of NAFLD was 36% (n = 2,299) and 564 (9%) were current smokers. Smokers had significantly higher GGT levels in the presence of NAFLD (P < 0.001). After multivariable adjustment, current smoking was associated with 4.65 IU/L higher GGT level, P < 0.001, compared to non-smokers. When stratified by NAFLD, the magnitude of this association was higher in subjects with NAFLD (β-coefficient: 11.12; 95% confidence interval (CI): 5.76 - 16.48; P < 0.001); however, no such relationship was observed in those without NAFLD (β: -0.02; 95% CI: -3.59, 3.56; P = 0.992). Overall the interaction of NAFLD and smoking with GGT levels as markers of oxidative stress was statistically significant. Conclusions: Smoking is independently associated with significantly increased oxidative stress as measured by GGT level.