Low serum testosterone is associated with adverse outcome in men with cirrhosis independent of the MELD score

Abstract

Introduction: Low serum testosterone has been retrospectively associated with mortality in men on the liver transplant waitlist. The impact of testosterone deficiency on other outcomes has not previously been assessed. Methods: We conducted a single centre prospective observational study of all men with cirrhosis seen between 2013 and 2014. Baseline data included sex hormone profile, MELD score and standard biochemistry. Outcomes were recorded over 12 months including major infection, liver transplantation and death. Results: Of 268 cirrhotic men, the median MELD score was 10 [8; 15] and median serum testosterone 17.4nmol/L [8.9, 25.0]. During the study period, 32 (12%) men died, 18 (7%) received a liver transplant and 51 (19%) suffered a major infection. Mortality markedly increased when total testosterone fell below a threshold value of 8.3nmol/L and this cut-off was used for further analysis. Testosterone below 8.3nmol/L was associated with the combined outcome of death or transplantation independently of the MELD score (HR 2.36 [1.16, 4.81], p=0.02 for testosterone, (HR 1.22 [1.18, 1.27], p<0.001 for MELD). Low total testosterone was also an independent risk factor for major infection (HR 3.61 [1.61, 8.06], p<0.001) and near significant for mortality alone (HR 2.39 [0.97, 5.88], p=0.057). Low free testosterone (<139pmol/L) was similarly independently associated with death or transplantation (HR 2.43 [1.12, 5.29], p=0.03) and infection (HR 3.3 [1.46, 7.46], p=0.004). Conclusions: Low testosterone is a novel prognostic marker in men with cirrhosis that is numerically associated with increased mortality or need for transplantation, as well as risk for major infection. Interventional studies of testosterone therapy are required to investigate whether correcting low testosterone can reduce mortality and improve other clinical outcomes.