Dam Gitte, Sørensen Michael, Munk Ole Lajord, Keiding Susanne
Department of Medicine V (Hepatology), Aarhus University Hospital, Aarhus, Denmark.
Scand J Gastroenterol. 2009;44(7):867-71. doi: 10.1080/00365520902929856.
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.
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.
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.
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.
通过对近期饮酒的酒精性肝硬化患者和健康受试者肝脏乙醇消除的动力学分析，探讨酗酒者乙醇消除增加是否可归因于通过乙醇脱氢酶（ADH；米氏常数约为0.2 mM）或微粒体乙醇氧化系统（MEOS；米氏常数10 mM）代谢的增加。另一个目的是研究低动脉乙醇浓度下乙醇的全身清除率是否可作为肝血流量的衡量指标。
6例酒精性肝硬化患者在戒酒2天后入组，同时纳入6名健康受试者。乙醇以递增剂量连续输注6次。测量动脉血和肝静脉血中的乙醇浓度；同时测量肝血流量。根据完整肝脏酶促消除的正弦灌注模型计算动力学参数。
健康受试者乙醇的平均肝脏米氏常数为0.16 mM（范围0.09 - 0.36），肝硬化患者为0.36 mM（范围0.16 - 0.69）（p>0.3），均与ADH的米氏常数相符。两组受试者的最大反应速度值相似（p>0.3）。两组中乙醇的肝外消除均占总消除的50%以上，这使得不能将全身清除率用作肝血流量的衡量指标。
结果支持以下假设，即ADH仍然是近期饮酒的酒精性肝硬化患者肝脏消除乙醇的主要途径。我们将此解释为反对MEOS在体内有显著作用的证据。
