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.

Figure 1

Blood concentrations of ethanol in an artery (●) and a liver vein (○) in a patient with cirrhosis (no. 5) during 5 periods of successive ethanol infusions in increasing doses of 0.45, 0.89, 1.23, 1.51 and 1.90 mmol min⁻¹.