Raised sympathetic activity and blood ammonia could increase sensitivity to infections in patients with cirrhosis and refractory ascites who are using beta-blockers

Abstract

We read with interest the study by Sersté et al. who found a negative impact of beta-blockers on survival in patients with cirrhosis and refractory ascites.1 Interestingly, 79.5% of patients with a specified cause of death died of sepsis, suggesting an association between chronic use of beta-blockers and development of bacterial infections, yet the authors did not provide an explanation. We suggest that raised blood norepinephrine (NE) and ammonia levels could contribute to increased vulnerability to bacterial infections in patients with refractory ascites who are taking beta-blockers. Circulating NE levels can be increased in cirrhosis due to reduced effective blood volume, impaired liver metabolism, portosystemic shunts, and propranolol treatment.2, 3 Patients with refractory ascites are commonly characterized by markedly increased plasma NE levels.2 High NE levels have been shown to suppress neutrophil chemotaxis4 and phagocytosis5 as well as to inhibit macrophage proliferation and promote their apoptosis.6 In the study of Sersté et al., beta-blocker–treated patients had worse liver function and systemic hemodynamics, which together with the presence of collaterals and propranolol treatment could result in higher NE concentration compared to the nontreatment group. Blood ammonia can also impair neutrophil phagocytosing function in cirrhosis7 and increases significantly with the grade of liver disease severity and esophageal varices,8 and after propranolol administration.9 Consequently, blood ammonia levels could be higher in the group treated with beta-blockers, which matches with the higher incidence of encephalopathy in these patients. We conclude that data regarding blood NE and ammonia concentration would be useful for the interpretation of the observations of Sersté et al. Georgios N. Kalambokis M.D.*, Epameinondas V. Tsianos M.D., Ph.D.*, * First Division of Internal Medicine and Hepato-Gastroenterology Unit, Medical School of Ioannina, Ioannina, Greece.