Amino acid challenge in patients with cirrhosis: a model for the assessment of treatments for hepatic encephalopathy.
OBJECTIVE
To mimic episodic hepatic encephalopathy after gastrointestinal bleeding under controlled conditions, cirrhotic patients were challenged with an amino acid mixture of comparable composition to haemoglobin.


METHODS
Basal EEG, psychometric score (HE test), reaction times and venous blood ammonia were recorded. Following a 54 or 108 gm oral amino acid challenge, blood ammonia levels and EEG were recorded at 30-min intervals, and psychometric testing was repeated at 180 min. Ten controls (57 +/- 2) and 31 cirrhotics (52 +/- 2) of which 21 were Child's grade A or B and 10 grade C underwent the challenge. Nine had a transjugular intrahepatic porta-systemic shunt in situ.


RESULTS
Seventeen patients had abnormal baseline HE scores. Basal blood ammonia and reaction time A were significantly greater in patients (52 +/- 5 micromol/l and 478 +/- 20 ms, respectively) than controls (19 +/- 2 micromol/l and 372 +/- 14 ms) (P < 0.001). Following the challenge, in patients with advanced liver disease (Child's grade B and C) the slowing of reaction time A (+85 +/- 38 and +71 +/- 31 ms, respectively; P < 0.03) and EEG (ratio of slow to fast wave activity +0.31 +/- 0.12 and +0.58 +/- 0.19; P < 0.02) were significantly greater than in controls (-3.3 +/- 8 ms and 0.00 +/- 0.03, respectively). Patients with an abnormal basal HE score had the most pronounced changes (reaction time A +110 +/- 39 ms, P < 0.01, EEG +0.52 +/- 13, P < 0.01, respectively). The change in EEG ratio correlated with the dose of amino acid administered (r = 0.96; P < 0.008).


CONCLUSIONS
The amino acid challenge constitutes a reproducible human model of episodic, Type C hepatic encephalopathy unaffected by the complications usually encountered in clinical practice.
Douglass
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Department of Medicine, University of Newcastle upon Tyne, UK.
Al Mardini
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Record
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D000596:Amino Acids / Q000008:administration & dosage / Q000737:chemistry; D000641:Ammonia / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005260:Female; D006454:Hemoglobins / Q000737:chemistry; D006501:Hepatic Encephalopathy / Q000097:blood / Q000139:chemically induced* / Q000209:etiology* / Q000523:psychology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D019168:Portasystemic Shunt, Transjugular Intrahepatic; D011594:Psychometrics; D011930:Reaction Time / Q000187:drug effects
D000596:Amino Acids; D006454:Hemoglobins; D000641:Ammonia