Amino acid challenge in patients with cirrhosis: a model for the assessment of treatments for hepatic encephalopathy

Background/Aims: 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 IIE scores. Basal blood ammonia and reaction time A were significantly greater in patients (52 +/- 5 mu mol/l and 478 +/- 20 ms, respectively) than controls (19 +/- 2 mu mol/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). Conclusion: The amino acid challenge constitutes a reproducible human model of episodic, Type C hepatic encephalopathy unaffected by the complications usually encountered in clinical practice. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.