Low serum testosterone is associated with adverse outcome in men with cirrhosis independent of the model for end‐stage liver disease score

Abstract

Low serum testosterone has been retrospectively associated with mortality in men on the liver transplant waiting list. The impact of testosterone deficiency on other outcomes has not previously been assessed. We conducted a single center prospective observational study of all men with cirrhosis seen between 2013 and 2014. Baseline data included sex hormone profile, Model for End-Stage Liver Disease (MELD) score, and standard biochemistry. Outcomes were recorded over 12 months including major infection, liver transplantation, and death. Of 268 cirrhotic men, the median MELD score was 10 (interquartile range [IQR], 8-15) and median serum testosterone was 17.4 nmol/L (IQR, 8.9-25.0 nmol/L). 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 8.3 nmol/L, and this cutoff was used for further analysis. Testosterone below 8.3 nmol/L was associated with the combined outcome of death or transplantation independently of the MELD score (hazard ratio [HR], 2.36; IQR, 1.16-4.81; P = 0.02) for testosterone (and HR, 1.22; IQR, 1.18-1.27; P < 0.001 for MELD). Low total testosterone was also an independent risk factor for major infection (HR, 3.61; IQR, 1.61-8.06; P < 0.001) and nearly significant for mortality alone (HR, 2.39; IQR, 0.97-5.88; P = 0.057). Low free testosterone (<139 pmol/L) was similarly independently associated with death or transplantation (HR, 2.43; IQR, 1.12-5.29; P = 0.03) and infection (HR, 3.3; IQR, 1.46-7.46; P = 0.004). In conclusion, 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. Liver Transplantation 22 1482-1490 2016 AASLD.

Dysbalanced sex hormone status is an independent predictor of decompensation and mortality in patients with liver cirrhosis

“…Similarly, inflammatory markers are commonly elevated in patients with cirrhosis, which is a consequence of endotoxemia due to pathological bacterial translocation from the gut . Low T was found as an independent risk factor for major infection, therefore confirming the pathophysiologic rationale in a clinical study and suggesting low T as a marker not only of disease severity but also increased inflammation. Furthermore, an inverse relationship between C‐reactive protein and T has been described .…”

“…Low T has been previously described as an independent risk factor for mortality and major infection in cirrhosis. Low median T levels have been described in patients with severe HE, who were admitted to hospital, as well as patients with ascites .…”

“…Low androgens and elevated serum estrone were associated with higher Model for End‐stage Liver Disease (MELD) score and individual adverse health outcomes . Association of low T with mortality within 12 months of follow‐up was also described, but no impact on hepatic decompensation . Furthermore, hepatic steatosis and presence of non‐alcoholic fatty liver disease is significantly associated with low serum T levels .…”

Loss of paraspinal muscle mass is a gender‐specific consequence of cirrhosis that predicts complications and death

“…Nevertheless, it does not provide further insights into molecular mechanisms behind this observation. Sex hormones such as testosterone and inappropriate autophagy may play an important role …”

“…Sex hormones such as testosterone and inappropriate autophagy may play an important role. 7,[27][28][29] To date, it is still debated as to whether the skeletal muscle mass is a reliable prognosticator for post-transplant survival. Whereas we and others 13,22,30,31 could not show an association, a few groups have reported a survival benefit with high muscle mass.…”