Serum SHBG Is Associated With the Development and Regression of Nonalcoholic Fatty Liver Disease: A Prospective Study

Context: SHBG, a homodimeric glycoprotein produced by hepatocytes has been shown to be associated with metabolic disorders. Whether circulating SHBG levels are predictive of later risk of nonalcoholic fatty liver disease (NAFLD) remains unknown. In this study, we prospectively investigated the association between SHBG and NAFLD progression through a community-based cohort comprising 3389 Chinese adults. Methods: NAFLD was diagnosed using abdominal ultrasonography. Serum SHBG levels were measured by chemiluminescent enzyme immunometric assay, and their relationship with NAFLD development and regression was investigated after a mean follow-up of 3.09 years using multivariable logistic regression. Results: Basal SHBG was negatively associated with NAFLD development, with a fully adjusted odds ratio (OR) and its 95% confidence interval (CI) of 0.22 (0.12-0.40) (P < .001). In contrast, basal SHBG was positively associated with NAFLD regression, with a fully adjusted OR of 4.83 (2.38-9.81) (P <.001). Multiple-stepwise logistic regression analysis showed that SHBG concentration was an independent predictor of NAFLD development (OR, 0.28 [0.18-0.45]; P <.001) and regression (OR, 3.89 [2.43-6.22]; P <.001). In addition, the area under the receiver operating characteristic curves were 0.764 (95% CI, 0.740-0.787) and 0.762 (95% CI, 0.738-0.785) for the prediction models of NAFLD development and regression, respectively. Conclusions: Serum SHBG concentration is associated with the development and regression of NAFLD; moreover, it can be a potential biomarker for predicting NAFLD progression, and also a novel preventive and therapeutic target for NAFLD.