Patients with
liver cirrhosis with normal neurological and mental status examination may present minimal forms of
hepatic encephalopathy, showing intellectual function impairment that cannot be detected through general clinical examination but can be unveiled using specific neuropsychological or neurophysiological examination. Evaluation of minimal
hepatic encephalopathy (MHE) in cirrhotic patients would have prognostic value. The psychometric
hepatic encephalopathy score (PHES) has been recommended as the "gold standard" in the diagnosis of MHE. Altered modulation of
cyclic GMP (cGMP) levels in the brain seems to be responsible for the impairment of some types of cognitive function in
liver disease. In animal models of
liver disease, some of the alterations in modulation of cGMP levels in the brain are reproduced in lymphocytes. The aim of the present work was to assess whether there is a correlation between the alterations in different parameters involved in modulation of cGMP levels and the presence of MHE in patients with
liver disease. We studied in 46 patients with
liver cirrhosis and 26 controls the performance in the PHES battery of psychometric tests and the critical flicker frequency (CFF), the concentration of cGMP in plasma and lymphocytes, activation of
guanylate cyclase by
nitric oxide (NO) in lymphocytes, and several parameters likely involved in altered cGMP homeostasis in
liver disease such as
ammonia, NO metabolites, and
atrial natriuretic peptide (
ANP). Activation of
guanylate cyclase by NO in lymphocytes and cGMP in plasma were higher and CFF lower in patients with MHE than in patients without MHE.
Ammonia,
ANP, and metabolites of NO were higher in patients than in controls but were no different in patients with or without MHE. Alteration in activation of
guanylate cyclase by NO in lymphocytes correlates with PHES performance, CFF, and
ammonia levels. This suggests that altered modulation of
guanylate cyclase by NO in lymphocytes would reflect a parallel alteration in the brain occurring in patients with MHE that would be involved in their
cognitive impairment.