SUN-623 Androgen Receptor Expression in Men With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Abstract A. Goffinet: None. J. Newman: None. O. Marks: None. J. Brunojo: None. G. Ling: None. A. Jain: None. K. Qureshi: None. B.A. Neuschwander-Tetri: None. S. Dhindsa: None. Background: Approximately one third of men with obesity or type 2 diabetes have subnormal free and bioavailable testosterone (T) concentrations. Low free T is also associated with non-alcoholic fatty liver disease, but no study has evaluated androgen receptor (AR) expression in men with MASLD. Methods: Study volunteers were recruited from the endocrinology and hepatology clinics. Men with liver diseases other than MASLD, >14 drinks per week or those taking T therapy were excluded. Participants provided a fasting blood sample and underwent liver elastography (Fibroscan). Serum free T concentrations were measured by liquid chromatography-mass spectrometry and equilibrium dialysis. Mononuclear cells (MNC) were separated, and expression of AR was measured by real-time reverse transcription–polymerase chain reaction (RT-PCR). MASLD was defined as hepatic steatosis (controlled attenuation parameter >260 db/m) with type 2 diabetes or BMI >25 kg/m2 or metabolic dysfunction. Volunteers without steatosis were labeled as non-MASLD. Metabolic dysfunction-associated steatohepatitis (MASH) was defined as MASLD + serum ALT ≥ 40 IU/L or biopsy proven steatohepatitis. MASLD patients without MASH were labeled as MASL. Results are presented as mean ± SD for normally distributed data and median [25th, 75th percentile] for non-normal data. Non-normal data were log transformed for parametric tests. Comparisons among groups were made by t-test or ANOVA. Results: The study included 86 men with MASLD (48 with MASL and 38 with MASH) and 21 men without MASLD. The median age was similar in 3 groups: 55[46, 59], 52[44, 60] and 50[35, 58] years in non-MASLD, MASL and MASH respectively (p=0.53). Non-MASLD men had lower BMI than MASL and MASH groups (27[23, 30], 35[31, 40] and 35[30, 41] kg/m2 respectively, p<0.001). Non-MASLD group had lower steatosis (222[155, 247], 331[297, 376] and 367[327, 384], p<0.001) and fibrosis (4.8[4.1, 5.8], 7.6[4.6, 12.1], 8.5[5.8, 12.4] kPA, p<0.001] measured on fibroscan as compared to MASL and MASH groups. Type 2 diabetes was present in 43%, 83% and 53% of non-MASLD, MASL and MASH groups. Mean hemoglobin A1c of the volunteers with diabetes was 7.9±1.7% and it did not differ among the 3 groups (p=0.87). The AR expression was lower in men with MASLD than non-MASLD (relative units 0.87±0.48 vs 1.19±0.69, p=0.05). The AR expression in MASH group was 30% lower than non-MASLD men (0.82±0.40, p=0.04) but was not different than MASL group (0.91±0.53, p=0.44). The free T concentrations were similar in MASH, MASL and non-MASLD groups (49[40, 66], 51[42, 68] vs 59[41, 92] respectively, p=0.54). Conclusion: We found that despite similar free T concentrations, men MASH had lower expression of AR in MNC than those without MASLD. Future studies should investigate the role of AR and androgen signaling in hepatocytes or liver macrophages on the progression of MASLD. Sunday, June 2, 2024