Stauch S, Kircheis G, Adler G, Beckh K, Ditschuneit H, Görtelmeyer R, Hendricks R, Heuser A, Karoff C, Malfertheiner P, Mayer D, Rösch W, Steffens J
Hospital Nordwest, Dept. of Internal Medicine, Frankfurt/Main, Germany.
J Hepatol. 1998 May;28(5):856-64. doi: 10.1016/s0168-8278(98)80237-7.
BACKGROUND/AIMS: In the current state of knowledge of the pathophysiology of hepatic encephalopathy, a reduction in hyperammonemia is the most important evidence of effective treatment. Therefore, the therapeutic efficacy of oral L-ornithine-L-aspartate, which improves impaired ammonia detoxification, was investigated in patients with cirrhosis, hyperammonemia and stable, overt, chronic hepatic encephalopathy, and in subclinical hepatic encephalopathy in a randomized, double-blind, placebo-controlled clinical trial.
Oral L-ornithine-L-aspartate was administered three times daily at fixed times for 14 consecutive days in a total dose of 18 g per day. The design was chosen to prevent an increase in ammonia induced by a protein meal of 0.25 g/kg body weight, given at the start of the daily treatment period. Efficacy variables were: fasting and postprandial ammonia concentration, Number-Connection-Test time, mental state grades, and a Portosystemic Encephalopathy Index. Analyses were based on the total study sample of 32 placebo- and 34 L-ornithine-L-aspartate-treated patients as well as on the subgroup samples in the overt (20 placebo- and 23 L-ornithine-L-aspartate-treated) and subclinical hepatic encephalopathy (12 placebo- and 11 L-ornithine-L-aspartate-treated) patients.
Number Connection Test performance times (p<0.01) as well as fasting (p<0.01) and postprandial (p<0.05) venous blood ammonia concentrations in the L-ornithine-L-aspartate-treated group showed improvement in comparison to placebo. Also, the mental state grade (p<0.05) and the Portosystemic Encephalopathy Index (p<0.01), improved to a much greater degree in the L-ornithine-L-aspartate group than in the placebo group. Adverse events were observed in neither the placebo nor the L-ornithine-L-aspartate-treated patients.
Oral L-ornithine-L-aspartate is a safe, well-tolerated treatment with a good compliance rate and a beneficial therapeutic effect in patients with cirrhosis and stable, overt, chronic hepatic encephalopathy.
背景/目的：在目前对肝性脑病病理生理学的认识水平下，高氨血症的降低是有效治疗的最重要证据。因此，在一项随机、双盲、安慰剂对照的临床试验中，对口服L-鸟氨酸-L-天冬氨酸改善氨解毒障碍的治疗效果进行了研究，该试验纳入了肝硬化、高氨血症以及稳定、显性、慢性肝性脑病患者和亚临床肝性脑病患者。
口服L-鸟氨酸-L-天冬氨酸，每天固定时间给药3次，连续14天，总剂量为每天18克。该设计旨在防止在每日治疗期开始时给予0.25克/千克体重的蛋白质餐引起氨水平升高。疗效变量包括：空腹和餐后氨浓度、数字连接试验时间、精神状态分级以及门体性脑病指数。分析基于32名接受安慰剂治疗和34名接受L-鸟氨酸-L-天冬氨酸治疗患者的总研究样本，以及显性肝性脑病（20名接受安慰剂治疗和23名接受L-鸟氨酸-L-天冬氨酸治疗）和亚临床肝性脑病（12名接受安慰剂治疗和11名接受L-鸟氨酸-L-天冬氨酸治疗）患者的亚组样本。
与安慰剂相比，L-鸟氨酸-L-天冬氨酸治疗组的数字连接试验执行时间（p<0.01）以及空腹（p<0.01）和餐后（p<0.05）静脉血氨浓度均有所改善。此外，L-鸟氨酸-L-天冬氨酸组的精神状态分级（p<0.05）和门体性脑病指数（p<0.01）的改善程度远大于安慰剂组。安慰剂组和L-鸟氨酸-L-天冬氨酸治疗组均未观察到不良事件。
口服L-鸟氨酸-L-天冬氨酸是一种安全、耐受性良好的治疗方法，依从率高，对肝硬化和稳定、显性、慢性肝性脑病患者具有有益的治疗效果。
