High sex hormone-binding globulin concentration is a risk factor for high fibrosis-4 index in middle-aged Japanese men

• Published in: ENDOCRINE JOURNAL Vol. 66; no. 7; pp. 637 - 645
• Main Authors: Fujihara, Yuya, Hamanoue, Nobuya, Yano, Hiromi, Tanabe, Makito, Akehi, Yuko, Nomiyama, Takashi, Yanase, Toshihiko
• Format: Journal Article
• Language: English
• Published: Japan The Japan Endocrine Society 01-01-2019; Japan Science and Technology Agency
• Subjects: Adult; Biomarkers - analysis; Biomarkers - blood; Cholesterol; Fatty liver; Fibrosis; Fibrosis - blood; Fibrosis - diagnosis; Fibrosis - epidemiology; Fibrosis-4 index; Globulins; Health Status Indicators; Homeostasis; Humans; Japan - epidemiology; Liver; Liver Cirrhosis - blood; Liver Cirrhosis - diagnosis; Liver Cirrhosis - epidemiology; Liver diseases; Liver fibrosis; Male; Menopause; Metabolic syndrome; Metabolic Syndrome - blood; Metabolic Syndrome - diagnosis; Metabolic Syndrome - epidemiology; Middle Aged; Non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - diagnosis; Non-alcoholic Fatty Liver Disease - epidemiology; Risk Factors; Sex hormone-binding globulin; Sex Hormone-Binding Globulin - analysis; Sex Hormone-Binding Globulin - metabolism; Sex hormones; Statistical analysis; Testosterone; Testosterone - blood; Urea; Japan; Sex hormone-binding globulin; Testosterone; Fibrosis-4 index; Liver fibrosis; Non-alcoholic fatty liver disease
• ISSN: 0918-8959; 1348-4540
• DOI: 10.1507/endocrj.EJ18-0505

Low endogenous testosterone and sex hormone-binding globulin (SHBG) concentrations have been reported to be associated with metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). However, little is known about the relationships between testosterone or SHBG and liver fibrosis in NAFLD. Thus, we aimed to clarify the relationships between serum testosterone or SHBG concentration and fibrosis-4 (FIB-4) index, a marker of liver fibrosis. Serum testosterone was assayed in various forms (total testosterone [TT], calculated free testosterone [cFT], calculated bioavailable testosterone [cbT], and SHBG) and metabolic markers were also measured in 363 Japanese men (mean age 51.1 ± 8.7 years) at routine health examinations. We then attempted to identify the factors contributing to liver fibrosis by investigating the associations between the metabolic markers, including testosterone, and FIB-4 index. People with a relatively high FIB-4 index (≥1.3) demonstrated lower cFT, cbT, homeostasis model assessment (HOMA)-β, low-density lipoprotein-cholesterol, and blood urea nitrogen, but higher SHBG, than those with a lower FIB-4 index (<1.3). There were no significant differences in HbA1c, fasting glucose concentration, HOMA-R, or metabolic syndrome prevalence between the two groups. Binary regression analysis revealed that SHBG ≥52 nmol/L and cFT <8.0 ng/dL were statistically significant risk factors for FIB-4 index ≥1.3. Receiver operating characteristic analysis revealed that cFT <7.62 ng/dL (area under the curve [AUC] = 0.639) and SHBG ≥49.8 nmol/L (AUC = 0.649) were the strongest risk factors for FIB-4 index ≥1.3. In contrast to previous findings showing low SHBG concentrations in NAFLD, we provide evidence that high SHBG and low bioactive testosterone are associated with liver fibrosis.