Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: a prospective study with time-dependent analysis.
OBJECTIVE
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.
Guevara
Mónica
M
Liver Unit, Hospital Clinic, University of Barcelona, Villarroel 170, Barcelona, Spain. mguevara@clinic.ub.es
Baccaro
M E
ME
Torre
Aldo
A
Gómez-Ansón
Beatriz
B
Ríos
José
J
Torres
Ferrán
F
Rami
Lorena
L
Monté-Rubio
Gemma C
GC
Martín-Llahí
Marta
M
Arroyo
Vicente
V
Ginès
Pere
P
D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D001663:Bilirubin / Q000097:blood; D001923:Brain Chemistry / Q000502:physiology; D003401:Creatine / Q000032:analysis; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D018698:Glutamic Acid / Q000032:analysis; D005973:Glutamine / Q000032:analysis; D006501:Hepatic Encephalopathy / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D007010:Hyponatremia / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012964:Sodium / Q000097:blood*; D013997:Time Factors
D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D012964:Sodium; D003404:Creatinine; D003401:Creatine; D001663:Bilirubin