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The pathogenesis of hepatic encephalopathy (HE) is unknown. Many theories have been proposed. Most established therapies are based on such theories but since no theory has have ever been proved, therapies have to be considered empiric. The spectrum of HE ranges from minimal cerebral functional deficits, which can only be found by sensitive psychometric tests, to coma with signs of decerebration. HE has arbitrarily been divided into stages. A number of precipitating factors are known and the first line of therapy should always be the elimination of these factors. The differential diagnosis includes all states of impaired consciousness and deficits in cerebral function in patients with chronic liver disease, and clinical and biochemical tests to differentiate are indicated. The therapeutic options for HE include: protein restriction only for a limited time in comatous patients; nonabsorbable antibiotics (aminoglycosides), which because of adverse effects are also limited to higher grades of HE: intestinal cleansing which is applicable in all degrees of HE; lactulose, branched chain aminoacids and ornithin aspartate which have been proven to be effective and can be applied long term in patients with lower grades of HE.

Forty patients with chronic liver disease and portal hypertension but without clinical signs of portasystemic encephalopathy (15 patients with nonalcoholic cirrhosis, 15 patients with alcoholic cirrhosis, and 10 patients with minimal EEG changes) and a control group of 12 patients with chronic alcohol pancreatitis were studied using an extensive psychometric program, which, in the same form, is used for expert reports on driving capacity. Of the cirrhotic patients, 60% were considered unfit to drive; in 25% driving capacity was questionable, 15% (only nonalcoholic cirrhotics) were considered fit to drive. In contrast 75% of the patients with alcoholic pancreatitis were considered fit to drive. Major defects were found only in three heavy alcoholics. Patients with alcoholic cirrhosis scored lower than patients with nonalcoholic cirrhosis. This was due to differences in liver function rather than to the effect of alcohol consumption. Patients with minimal EEG changes were practically all considered unfit to drive.

SUMMARY Monooxygenase enzymes are involved in the biotransformation of drugs and of environmental carcinogens. The activity of 7-ethoxycoumarin 0-deethylase and associated NADPHcytochrome c reductase was determined in 9000 g supernatant from bioptically obtained liver specimens from patients with various liver diseases in order to study in vitro drug metabolising capacity. Monooxygenase and reductase activity was significantly higher in the livers of 21 patients with alcoholic liver disease (fatty liver, alcoholic hepatitis, cirrhosis of the liver) than in 22 normal controls or in six patients with chronic active hepatitis. The raised activity of drug-metabolising enzymes obtained from alcoholics with liver damage differs from normal values found in five alcoholics without liver disease. Both groups were comparable in respect to the amount of alcohol consumed and duration of abuse. A strikingly low monooxygenase activity was observed in eight patients with cirrhosis of the liver and ascites, with, however, no apparent effect on reductase activity. The results show that alcoholic liver disease is associated with enhanced monooxygenase and reductase activity, but alcoholism, per se, is not. This rise of drug-metabolising enzyme activity could lead to selectively increased rates of biotransformation in patients with alcoholic liver damage.

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