Endocrine Abstracts

Background: Metabolic dysfunction associated fatty liver disease (MAFLD), the leading cause of chronic liver disease, is defined as the presence of hepatic steatosis and metabolic risk factors. Both testosterone and estradiol seem to have a pivotal role in hepatic lipid homeostasis, although underlying mechanisms are still unclear. Low testosterone serum levels result independently associated with MAFLD, but no studies so far evaluated MAFLD prevalence and severity in hypogonadal men.

Aim of the study: To evaluate MAFLD prevalence and severity in a cohort of hypogonadal men.

Methods: A prospective, observational, clinical trial was conducted enrolling hypogonadal men (testosterone serum levels <3 ng/ml) and collecting medical history, anthropometrical characteristics, hormonal (testosterone, estradiol, sex hormone binding globulin [SHBG] and prolactin) and biochemical (liver enzymes, lipid profile, glycemia and glycated haemoglobin) parameters. Each patient underwent hepatic ultrasound to evaluate the presence and grade of steatosis, and Fibroscan® and 2-dimensional shear weave elastography (2D-SWE) techniques for the assessment of liver stiffness. A liver stiffness ± 8 kPa was considered diagnostic for liver fibrosis.

Results: Twenty-six hypogonadal men (age 59.9±13.8 years, body mass index 33.9±7.4 kg/m²) were enrolled, of which 20 (76.9%) presented secondary hypogonadism, and six (23.1%) a primary form. Eighteen patients (69.2%) were already under androgen replacement therapy (mean treatment duration 4.5±3.7 years), presenting mean testosterone serum levels above the lower level of the reference range (3.9±2.9 ng/ml). Hepatic steatosis was detected in 16 patients (61.5%), divided into mild (7.7%), moderate (26.9%) and severe (26.9%) grades. No difference in liver steatosis presence/grade was detected between androgen-replaced patients compared to untreated ones. Liver stiffness was 6.8±5.4 KPa (IQR 16.2±7.1%) at Fibroscan® and 7.7±10.3 KPa (IQR/M 21.5±8.1%) at 2D-SWE. Liver fibrosis was detected in five men (19.2%) at Fibroscan® and in 4 (15.4%) at 2D-SWE. The presence of liver fibrosis according to both elastography techniques was not associated to any biochemical parameter. However, multivariate analysis showed that liver stiffness was predicted by alanine transaminase (ALT) (B: 0.780, P<0.005) and testosterone (B: -1.819, P=0.022) serum levels.

Discussion: Here, we demonstrated a high prevalence of liver steatosis in hypogonadal men, especially of moderate/severe grades. Moreover, using different elastography techniques, we highlighted an unexpectedly high prevalence of liver fibrosis, occurring in more than 15% of cases. Although our results need further confirmation in larger cohorts, the inverse correlation between liver stiffness and testosterone serum levels at least suggests the need to assess the presence of MAFLD in hypogonadal patients.