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

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.