Free testosterone concentration is inversely associated with markers of liver fibrosis in men with type 2 diabetes mellitus

Miyauchi, Shozo; Miyake, Teruki; Miyazaki, M; Eguchi, Toru; Niiya, Tetsuji; Yamamoto, Shin; Senba, Hidenori; Furukawa, Shinya; Matsuura, Bunzo; Hiasa, Yoichi

doi:10.1507/endocrj.ej17-0225

Cited by 13 publications

(7 citation statements)

References 31 publications

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“…Third, because the long‐term use of AVT might have the most significant role in the regression of liver fibrosis, it should be investigated whether the improvement in sarcopenia has additional role in the process of fibrosis regression. Of note, it would be plausible that significant liver fibrosis leads to reduced appetite, decreased testosterone levels, exacerbates catabolic state, leading to sarcopenia . Although the proportion of the medical treatment was statistically similar between sarcopenic and the nonsarcopenic groups (19.3% vs 24.1%, P = 0.523), detailed information regarding the phase of CHB, AVT (anti‐viral agents or genotypic mutation) and the corresponding AVT was not available for our cohort.…”

Section: Discussionmentioning

confidence: 98%

“…Of note, it would be plausible that significant liver fibrosis leads to reduced appetite, decreased testosterone levels, exacerbates catabolic state, leading to sarcopenia. 46,47 Although the proportion of the medical treatment was statistically similar between sarcopenic and the nonsarcopenic groups (19.…”

Section: Independent Association Between Sarcopenia and Significantmentioning

confidence: 98%

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Sarcopenia is associated with the risk of significant liver fibrosis in metabolically unhealthy subjects with chronic hepatitis B

Han

Lee

Kim

et al. 2018

Aliment Pharmacol Ther

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Section: Discussionmentioning

confidence: 98%

Section: Independent Association Between Sarcopenia and Significantmentioning

confidence: 98%

Sarcopenia is associated with the risk of significant liver fibrosis in metabolically unhealthy subjects with chronic hepatitis B

Han

Lee

Kim

et al. 2018

Aliment Pharmacol Ther

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“…However, the relationships between liver fibrosis indicators and the various types of testosterone measurement remain unclear. There has only been a single report that the FIB-4 index in T2DM is negatively correlated with FT [18], and no reports regarding the relationships between liver fibrosis indicators and SHBG.…”

mentioning

confidence: 99%

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

et al. 2019

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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.

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“…However, also these methods have limitations: ultrasonography has limited accuracy in detecting fatty liver when < 35% of hepatocytes have been affected [36], and performing liver biopsy for patients who do not meet indications raises ethical considerations. Given the limitations of instrumental and histological methods for measurement of liver fibrosis, scores based on serum markers have been demonstrated good tools for the prediction of severity of liver fibrosis [37] and are widely used both in the general population and in HIV-infected patients [21,36,[38][39][40].…”

Section: Discussionmentioning

confidence: 99%

Hypogonadism and liver fibrosis in HIV-infected patients

Quirós-Roldán

Porcelli

Pezzaioli

et al. 2021

J Endocrinol Invest

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Purpose Hypogonadism is frequent in HIV-infected men and might impact on metabolic and sexual health. Low testosterone results from either primary testicular damage, secondary hypothalamic-pituitary dysfunction, or from liver-derived sex-hormone-binding-globulin (SHBG) elevation, with consequent reduction of free testosterone. The relationship between liver fibrosis and hypogonadism in HIV-infected men is unknown. Aim of our study was to determine the prevalence and type of hypogonadism in a cohort of HIV-infected men and its relationship with liver fibrosis. Methods We performed a cross-sectional retrospective study including 107 HIV-infected men (median age 54 years) with hypogonadal symptoms. Based on total testosterone (TT), calculated free testosterone, and luteinizing hormone, five categories were identified: eugonadism, primary, secondary, normogonadotropic and compensated hypogonadism. Estimates of liver fibrosis were performed by aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores. Results Hypogonadism was found in 32/107 patients (30.8%), with normogonadotropic (10/107, 9.3%) and compensated (17/107, 15.8%) being the most frequent forms. Patients with secondary/normogonadotropic hypogonadism had higher body mass index (BMI) (p < 0001). Patients with compensated hypogonadism had longer HIV infection duration (p = 0.031), higher APRI (p = 0.035) and FIB-4 scores (p = 0.008), and higher HCV co-infection. Univariate analysis showed a direct significant correlation between APRI and TT (p = 0.006) and SHBG (p = 0.002), and between FIB-4 and SHBG (p = 0.045). Multivariate analysis showed that SHBG was independently associated with both liver fibrosis scores. Conclusion Overt and compensated hypogonadism are frequently observed among HIV-infected men. Whereas obesity is related to secondary hypogonadism, high SHBG levels, related to liver fibrosis degree and HCV co-infection, are responsible for compensated forms.

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Free testosterone concentration is inversely associated with markers of liver fibrosis in men with type 2 diabetes mellitus

Cited by 13 publications

References 31 publications

Sarcopenia is associated with the risk of significant liver fibrosis in metabolically unhealthy subjects with chronic hepatitis B

Sarcopenia is associated with the risk of significant liver fibrosis in metabolically unhealthy subjects with chronic hepatitis B

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

Hypogonadism and liver fibrosis in HIV-infected patients

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