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Hyponatremia Is a Risk Factor of Hepatic Encephalopathy in Patients With Cirrhosis

A Prospective Study With Time-Dependent Analysis

Guevara, Mónica1-3,7; Baccaro, M. E.1-3,7; Torre, Aldo1; Gómez-Ansón, Beatriz4; Ríos, José5; Torres, Ferrán5; Rami, Lorena6; Monté-Rubio, Gemma C.4; Martín-Llahí, Marta1-3; Arroyo, Vicente1-3; Ginès, Pere1-3

American Journal of Gastroenterology: June 2009 - Volume 104 - Issue 6 - p 1382–1389
ORIGINAL CONTRIBUTIONS: LIVER AND BILIARY TRACT
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OBJECTIVES: The aim of this study was to investigate whether hyponatremia is a risk factor of overt hepatic encephalopathy (HE) in cirrhosis.

METHODS: A total of 61 patients with cirrhosis were evaluated prospectively for 1 year and all episodes of overt HE were recorded. Predictive factors of HE were analyzed using a conditional model (Prentice, Williams, and Peterson) for recurrent events to assess the relationship between HE and time-dependent covariates. The effects of hyponatremia on the brain concentration of organic osmolytes were analyzed in 25 patients using 1H-magnetic resonance spectroscopy.

RESULTS: Twenty-eight of the 61 patients developed 57 episodes of overt HE during follow-up. Among a number of clinical and laboratory variables analyzed, the only independent predictive factors of overt HE were hyponatremia (serum sodium < 130 mEq/l), history of overt HE, serum bilirubin, and serum creatinine. Hyponatremia was associated with low brain concentration of organic osmolytes, particularlymyo-inositol (MI). Furthermore, patients with low brain MI levels had a higher probability of development of overt HE compared with that of patients with high brain MI levels.

CONCLUSIONS: In patients with cirrhosis, the existence of hyponatremia is a major risk factor of the development of overt HE. Treatment of hyponatremia may be a novel therapeutic approach to preventing HE in cirrhosis.

1Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain; 2Institut d'Investigacions Biomédiques August Pi-Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; 3Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Catalunya, Spain; 4Radiology Department, Hospital Clínic, University of Barcelona, Barcelona, Spain; 5Statistical Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain; 6Department of Neurology, Hospital Clínic, University of Barcelona, Barcelona, Spain; 7These authors contributed equally to this work.

Correspondence: Mónica Guevara, MD, Liver Unit, Hospital Clínic, Villarroel, 170, 08036, Barcelona, Spain.

E-mail: mguevara@clinic.ub.es

Received 25 July 2008; accepted 17 November 2008

© The American College of Gastroenterology 2009. All Rights Reserved.
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