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To the Editor:

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.

References

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  • 1
    Sersté T, Melot C, Francoz C, Durand F, Rautou PE, Valla D, et al. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. HEPATOLOGY 2010; 52: 1017-1022.
  • 2
    Stadlbauer V, Wright GA, Banaji M, Mukhopadhya A, Mookerjee RP, Moore K, et al. Relationship between activation of the sympathetic nervous system and renal blood flow autoregulation in cirrhosis. Gastroenterology 2008; 134: 111-119.
  • 3
    Bendtsen F, Henriksen JH, Sørensen TI, Christensen NJ. Effect of oral propranolol on circulating catecholamines in cirrhosis: relationship to severity of liver disease and splanchnic haemodynamics. J Hepatol 1990; 10: 198-204.
  • 4
    Deitch EA, Bridges RM. Stress hormones modulate neutrophil and lymphocyte activity in vitro. J Trauma 1987; 27: 1146-1154.
  • 5
    Gosain A, Gamelli RL, DiPietro LA. Norepinephrine-mediated suppression of phagocytosis by would neutrophils. J Surg Res 2009; 152: 311-318.
  • 6
    Brown SW, Meyers RT, Brennan KM, Rumble JM, Narasimhachari N, Perozzi EF, et al. Catecholamines in a macrophage cell line. J Neuroimmunol 2003; 135: 47-55.
  • 7
    Shawcross DL, Wright GA, Stadlbauer V, Hodges SJ, Davies NA, Wheeler-Jones C, et al. Ammonia impairs neutrophil phagocytic function in liver disease. HEPATOLOGY 2008; 48: 1202-1212.
  • 8
    Tarantino G, Citro V, Esposito P, Giaquinto S, de Leone A, Milan G, et al. Blood ammonia levels in liver cirrhosis: a clue for the presence of portosystemic collateral veins. BMC Gastroenterol 2009; 9: 21.
  • 9
    van Buuren HR, van der Velden PC, Koorevaar G, Silberbusch J. Propranolol increases arterial ammonia in liver cirrhosis. Lancet 1982; 2: 951-952.

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.