Free Testosterone Is Associated With Worse Survival in Patients With Advanced Chronic Liver Disease Awaiting Liver Transplantation

ABSTRACT Background and Aims Hypogonadism is frequent in AdvCLD and associated with frailty and poor outcomes. This study aimed to evaluate the association between free testosterone ( FT ) levels and all‐cause mortality in male patients with AdvCLD awaiting liver transplantation ( LT ), and to compare the prognostic value of FT with total testosterone ( TT ). Methods In this prospective cohort study, 191 male patients with AdvCLD awaiting LT underwent FT and TT evaluation. The primary outcome was all‐cause mortality, assessed using a competing‐risk model with LT as the competing event. Results Among the 191 patients, 41 (21.5%) had low FT levels. This group was more likely to have a higher Child‐Turcotte‐Pugh class and MELD ‐Na score, as well as higher proportion of individuals with a history of hepatic encephalopathy ( HE ) compared to those with normal FT levels ( p < 0.05). Patients with low FT also exhibited greater frailty (liver frailty index: 4.2 ± 0.8 vs. 3.6 ± 0.9, p < 0.001, respectively). After adjustment for MELD ‐Na, low FT was significantly associated with increased mortality risk (adjusted subdistribution hazard ratio [ aSHR ] 1.97; 95% CI : 1.07–3.61). Additionally, patients with low FT had a lower cumulative probability of undergoing LT compared to those with normal FT levels (43.4% vs. 74.3%). In contrast, low TT was not associated with mortality ( aSHR : 1.65; 95% CI : 0.90–3.02). Conclusion Low FT levels are independently associated with higher mortality and lower LT probability in men with AdvCLD and outperform TT as a prognostic marker. These findings support FT as a valuable biomarker to identify high‐risk patients and guide future interventional strategies.