Role of ammonia and inflammation in minimal hepatic encephalopathy.
BACKGROUND
Minimal hepatic encephalopathy (MHE) is common in cirrhosis but its pathophysiologic basis remains undefined. We evaluated whether the presence of MHE was associated with severity of liver disease, ammonia levels or the presence of inflammation and assessed factors determining neuropsychological deterioration accompanying induction of hyperammonemia.


METHODS
Eighty four cirrhotics were studied. A neuropsychological test battery was performed and blood taken for ammonia, WCC, CRP, nitrate/nitrite, IL-6 and amino acids, before and after, induction of hyperammonemia by administration of a solution mimicking the amino acid composition of haemoglobin (60) or placebo (24).


RESULTS
The presence and severity of MHE were independent of severity of liver disease and ammonia concentration but markers of inflammation were significantly higher in those with MHE compared with those without. Induction of hyperammonemia produced deterioration in one or more neuropsychological tests by > or =1 SD in 73.3%. This was independent of the magnitude of change in plasma ammonia and severity of liver disease but was significantly greater in those with more marked inflammation.


CONCLUSIONS
Our data show that inflammation is an important determinant of the presence and severity of MHE. The change in neuropsychological function following induced hyperammonemia is greater in those with more severe inflammation.
Shawcross
D L
DL
Liver Failure Group, The UCL Institute of Hepatology, Division of Medicine, University College London, 69-75 Chenies Mews, London, WC1E 6HX, UK. r.jalan@ucl.ac.uk
Wright
G
G
Olde Damink
S W M
SW
Jalan
R
R
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000008:administration & dosage* / Q000097:blood; D000641:Ammonia / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006501:Hepatic Encephalopathy / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D006801:Humans; D022124:Hyperammonemia / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008103:Liver Cirrhosis / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D012720:Severity of Illness Index
D000596:Amino Acids; D015415:Biomarkers; D015850:Interleukin-6; D009566:Nitrates; D009573:Nitrites; D000641:Ammonia; D002097:C-Reactive Protein