Sex Hormone Binding Globulin (SHBG) is a Marker of Liver Fibrosis in Men with Nonalcoholic Fatty Liver Disease (NAFLD)

Obesity leads to a decrease in sex hormone binding globulin (SHBG) concentrations, while cirrhosis is associated with increased SHBG in men. We evaluated whether serum SHBG concentrations can serve as a marker of fibrosis in men with nonalcoholic fatty liver disease (NAFLD).

Methods:

Men with obesity, type 2 diabetes or known NAFLD were recruited from the endocrinology and hepatology clinics. Participants underwent liver elastography (Fibroscan) and provided a fasting blood sample. Subjects with hepatic steatosis (controlled attenuation parameter >260 dB/m on Fibroscan) and/or fibrosis were included in the study. Study subjects were categorized as low (Lo), intermediate (Int), or high (Hi) probability of advanced fibrosis ( < 7.5, 7.5-14, >14 kPa) on Fibroscan. Serum SHBG, total and free testosterone concentrations were measured by electrochemiluminescence, liquid chromatography-mass spectrometry and equilibrium dialysis, respectively. Results are presented as mean ± standard deviation for normally distributed data and median [25th, 75th percentile] for non-normal data. Non-normal data were log transformed for parametric tests.

Results:

64 men with NAFLD participated in the study. Groups with Lo, Int or Hi probability of fibrosis comprised of 29, 21 and 14 men respectively. Mean age (48±12 years) and prevalence of diabetes (75%) were similar among the 3 groups. Mean BMI in group Lo (33±5 kg/m²) was lower (p < 0.05) than in groups Int (38±7 kg/m²) and Hi (40±10 kg/m²). Steatosis was also lower (p < 0.05) in group Lo (322±45 dB/m) than in groups Int (360±40 dB/m) and Hi (350±51 dB/m). Consistent with the known effect of obesity on lowering SHBG, median SHBG concentrations were higher in group Lo (29[22, 37] nmol/L) than in group Int (19[12, 25] nmol/L). However, SHBG concentrations were higher in group Hi (28[21, 51] nmol/L, p< 0.05) than group Int, despite similar BMI and hepatic steatosis in the two groups. Adjustment for age, BMI, or steatosis between groups did not change the results. Free testosterone, LH, FSH, hemoglobin A1c, AST, ALT, alkaline phosphatase, platelets, albumin, and total bilirubin concentrations were similar in the 3 groups. 45% of men had low free testosterone ( < 5 ng/dl).

Discussion/Conclusion:

SHBG concentrations are higher in men with a high probability of significant liver fibrosis, than in those with steatosis alone. SHBG follows a “U-relationship” in NAFLD; declining with steatosis and increasing in later stages with more fibrosis. SHBG should be measured in prospective follow up studies of men with NAFLD to evaluate its potential as a predictor of fibrosis or incorporation into multi-variable fibrosis scoring systems.