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 Childʹs 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 μmol/l and 478±20 ms, respectively) than controls (19±2 μmol/l and 372±14 ms) (P<0.001). Following the challenge, in patients with advanced liver disease (Childʹs 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.