Hepatic ethanol elimination kinetics in patients with cirrhosis

Abstract

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. Material and 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.

• Alcoholism
• alcohol dehydrogenase
• liver metabolism
• liver pathophysiology
• microsomal ethanol oxidizing system