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

Rafael Paternostro; Birgit B Heinisch; Thomas Reiberger; Mattias Mandorfer; Constanze Bardach; Katharina Lampichler; Berit Seeland; Remy Schwarzer; Michael Trauner; Markus Peck-Radosavljevic; Arnulf Ferlitsch

doi:10.1111/hepr.13253

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

Hepatol Res. 2019 Feb;49(2):201-211. doi: 10.1111/hepr.13253. Epub 2018 Oct 31.

Authors

Rafael Paternostro^{1

2}, Birgit B Heinisch^{1

2}, Thomas Reiberger^{1

2}, Mattias Mandorfer^{1

2}, Constanze Bardach³, Katharina Lampichler³, Berit Seeland^{1

2}, Remy Schwarzer^{1

2}, Michael Trauner², Markus Peck-Radosavljevic⁴, Arnulf Ferlitsch^{1

2}

Affiliations

¹ Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
² Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
³ Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
⁴ Division of Gastroenterology, Hepatology, Endocrinology and Nephrology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria.

Abstract

Aims: Endocrinological abnormalities, including low testosterone levels, are prevalent in cirrhosis. We assessed sexual hormone status in regard to hemodynamic abnormalities and its impact on hepatic decompensation and survival.

Methods: Males with cirrhosis were prospectively included in this study since 2010. Sexual hormones including bioavailable testosterone, total testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex hormone-binding globulin as well as Child-Pugh score, Model for End-stage Liver Disease (MELD) score, and hepatic venous pressure gradient were recorded. Sarcopenia was also assessed in patients with available computed tomography scans. Clinical follow-up for hepatic decompensation, liver transplantation, and death was recorded until May 2017.

Results: One hundred fourteen male cirrhotic patients were included: age 55 ± 9.4 years, MELD 13.5 (range, 7-20.7). Etiologies were alcoholic liver disease in 61(53.5%) patients, viral in 30 (26.3%) patients, and other in 23 (20.2%). Child-Pugh scores were A in 32 (28.1%) patients, B in 48 (42.1%), and C in 34 (29.8%). Levels of bioavailable testosterone and total testosterone decreased with advanced Child-Pugh score (P < 0.001 and P < 0.001) whereas prolactin increased (P = 0.002). Median bioavailable testosterone (0.8 ng/mL [0.1-2] vs. 1.68 ng/mL [0.07-2.65]; P = 0.004) and total testosterone (2.7 ng/mL [0.23-12.34] vs. 7 ng/mL [0.25-10]; P = 0.041) levels were lower in patients with severe portal hypertension (hepatic venous pressure gradient >12 mmHg). Median bioavailable testosterone (0.25 ng/mL [0.07-1.7] vs. 0.97 ng/mL [0.15-2.74)]; P = 0.017) and total testosterone levels (1.28 ng/mL [0.25-7.32] vs. 4.32 ng/mL [0.43-13.47]; P = 0.031) were significantly lower in sarcopenic patients. Median follow-up was 13 months (0.2-75 months) and liver-related events were recorded in 46 patients (40.4%; death, 31 [27.2%]). Low total testosterone was associated with an increased risk for hepatic decompensation and/or death, even after adjusting for Child-Pugh score, MELD, and other relevant factors (Child-Pugh score model: hazard ratio 2.503, 95% confidence interval, 1.214-5.157, P = 0.013; MELD model: hazard ratio 3.065, 95% confidence interval, 1.523-6.169, P = 0.002).

Conclusion: In parallel to increasing severity of cirrhosis, levels of testosterone decline whereas prolactin levels increase. However, low testosterone levels are independently associated with a higher risk for hepatic decompensation and mortality.

Keywords: cirrhosis; mortality; sexual hormone; testosterone.