Liver and Biliary Tract
Subject Category: Liver and Biliary Tract
Am J Gastroenterol 2009; 104:1382–1389; doi:10.1038/ajg.2009.293; published online 19 May 2009
Hyponatremia Is a Risk Factor of Hepatic Encephalopathy in Patients With Cirrhosis: A Prospective Study With Time-Dependent Analysis
Mónica Guevara1,2,3,7, M E Baccaro1,2,3,7, Aldo Torre1, Beatriz Gómez-Ansón4, José Ríos5, Ferrán Torres5, Lorena Rami6, Gemma C Monté-Rubio4, Marta Martín-Llahí1,2,3, Vicente Arroyo1,2,3 and Pere Ginès1,2,3
- 1Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain
- 2Institut d'Investigacions Biomèdiques 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
Correspondence: Mónica Guevara, MD, Liver Unit, Hospital Clínic, Villarroel, 170, 08036, Barcelona, Spain. E-mail: mguevara@clinic.ub.es
7These authors contributed equally to this work.
Received 25 July 2008; Accepted 17 November 2008; Published online 19 May 2009.
Abstract
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, particularly myo-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.
