Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: a prospective study with time-dependent analysis

Am J Gastroenterol. 2009 Jun;104(6):1382-9. doi: 10.1038/ajg.2009.293.

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 1 H-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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / analysis
  • Bilirubin / blood
  • Brain Chemistry / physiology
  • Creatine / analysis
  • Creatinine / blood
  • Female
  • Follow-Up Studies
  • Glutamic Acid / analysis
  • Glutamine / analysis
  • Hepatic Encephalopathy / diagnosis
  • Hepatic Encephalopathy / etiology*
  • Hepatic Encephalopathy / metabolism
  • Humans
  • Hyponatremia / blood
  • Hyponatremia / complications*
  • Hyponatremia / diagnosis
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / complications*
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Parietal Lobe
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Sodium / blood*
  • Time Factors

Substances

  • Glutamine
  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate
  • Sodium
  • Creatinine
  • Creatine
  • Bilirubin