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

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, folliclestimulating 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 liverrelated 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.

Impact of HSD17B13 rs72613567 genotype on hepatic decompensation and mortality in patients with portal hypertension

“…Although sex did not appear to modify the effect of HSD17B13 genotype on liver‐related events, we investigated serum testosterone levels in cohort B. Interestingly, we observed numerically lower serum levels of testosterone (Figure S4) in male patients harbouring the loss‐of‐function TA allele. As low testosterone levels have repeatedly been linked to liver‐related events by our group and others, a potential detrimental impact of the HSD17B13 TA allele in patients with ACLD via decreased testosterone biosynthesis warrants further study in a larger series of patients.…”

The value of different CT‐based methods for diagnosing low muscle mass and predicting mortality in patients with cirrhosis

“…Giving the detrimental effects of sarcopenia on liver‐related outcomes and mortality in patients with ACLD, reversing muscle‐loss represents a management priority in these patients . Sarcopenia in ACLD is multifactorial and the pathophysiology include protein‐malnutrition, increased proteolysis from skeletal muscles, accelerated starvation response, physical inactivity or humoral factors such as upregulation of myostatin as a result of hyperammonaemia or hypotestosteronism . Nutritional supplementation with branched chain amino acids (BCAAs) has been shown to improve liver‐related outcomes and muscle mass .…”

Assessment of muscle status and Sarcopenia in patients with liver cirrhosis

“…Women with sarcopenia may be at a more advanced stage of malnutrition because they have reached the point of requiring their muscle mass as an energy store. Also, the androgens deficiencies with hyperestrogenism in male patient with liver cirrhosis play a role in muscle status deterioration 23 . Also, we found that there was significant difference as regard BMI estimated by dry weight between sarcopenic and non sarcopenic patients (p<0.001) as all patients (100%) with low body weight (BMI<18.5) were sarcopenic.…”