Hepatic ethanol elimination kinetics in patients with cirrhosis.
OBJECTIVE
To address the question of whether increased ethanol elimination in alcoholics can be ascribed to increased metabolism via alcohol dehydrogenase (ADH; K(m) around 0.2 mM) or the microsomal ethanol-oxidizing system (MEOS; K(m) 10 mM) by kinetic analysis of hepatic ethanol elimination in recently drinking patients with alcoholic cirrhosis and healthy subjects. A further objective was to investigate whether systemic clearance of ethanol at low arterial ethanol concentrations can be used as a measure of hepatic blood flow.


METHODS
Six patients with alcoholic cirrhosis were enrolled after 2 days of abstinence, along with 6 healthy subjects. Ethanol was administered as 6 successive infusions in increasing doses. Arterial and hepatic venous blood concentrations of ethanol were measured; hepatic blood flow was measured simultaneously. Kinetic parameters were calculated according to the sinusoidal perfusion model of enzymatic elimination by the intact liver.


RESULTS
Mean hepatic K(m) for ethanol was 0.16 mM (range 0.09-0.36) in healthy subjects and 0.36 mM (range 0.16-0.69) in patients with cirrhosis (p>0.3), both compatible with the K(m) for ADH. The two groups of subjects had similar V(max) values (p>0.3). Extrahepatic elimination of ethanol accounted for more than 50% of total elimination in both groups, which precludes the use of systemic clearance as a measure of hepatic blood flow.


CONCLUSIONS
The results support the hypothesis that ADH remains the main pathway for hepatic elimination of ethanol in recently drinking patients with alcoholic cirrhosis. We interpret this as evidence against a significant contribution of MEOS in vivo.
Dam
Gitte
G
Department of Medicine V (Hepatology), Aarhus University Hospital, Aarhus, Denmark.
Sørensen
Michael
M
Munk
Ole Lajord
OL
Keiding
Susanne
S
D000328:Adult; D000368:Aged; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D016022:Case-Control Studies; D003287:Contrast Media; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000431:Ethanol / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007472:Iohexol; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D003287:Contrast Media; D000431:Ethanol; D007472:Iohexol; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; C092153:microsomal ethanol-oxidizing system