乳果糖对轻微型肝性脑病患者认知水平及生活质量的影响

背景:目前肝性脑病发病机制未完全清楚,可能以氨中毒学说最确实有据,乳果糖的降氨作用机制比较清楚,国内外关于乳果糖治疗肝性脑病的研究很多,但尚缺乏关于乳果糖长短程治疗与安慰剂对照治疗的比较研究。目的:采用乳果糖对轻微型肝性脑病患者进行长/短程治疗,并比较其对轻微型肝性脑病患者生活质量的影响。设计:病例-对照观察。单位:广州市第一人民医院老年病科。对象:于1998-06/2002-03在广州市第一人民医院老年病科就诊的连续的肝硬化患者中随机选择经数字连接试验,数字符号试验和/或诱发电位检查异常并配合治疗的轻微型肝性脑病患者60例,随机分为对照组、乳果糖短程组及长程组,每组20例。方法:对照组仅给予复合维生素B,2片/次,3次/d,治疗24周实验结束;乳果糖短程治疗组在此基础上再给予口服乳果糖15～90mL/d,治疗8周,长程组则给予口服乳果糖至24周。分别在第0,8,16,24周末进行生活质量(中国版)调查,并观察肝性脑病发生率。同时进行血氨浓度的实验室检测。主要观察指标:治疗过程中患者生活质量和血氨浓度的变化。结果:在治疗过程中,对照组1例失去联系,短程组1例交通意外死亡,长程组2例不能耐受腹泻的副作用退出。共56例完成治疗进入结果分析。①对照组、短程治疗组、长程治疗组6个月累积肝性脑病发生率分别为40%(8/20),30%(6/20),5%(1/20)。长程治疗组发生率均低于对照组及短程组,差异有显著性意义(P<0.05),但短程组与对照组差异无显著性意义(P>0.05)。②治疗后8,12,24周对照组、乳果糖短程组及长程组组间生活质量的环境领域评分差异无显著性意义(P>0.05),但在生活质量的生理、心理、社会关系领域差异均有显著性意义(P<0.05):其中第8周时乳果糖长程组、短程组均较对照组有明显改善,长短程组之间差异不显著;第16周时乳果糖长程组均较短程组和对照组有明显改善,短程组和对照组之间差异不显著;第24周时乳果糖长程组均明显好于对照组和短程组。③治疗后16,24周乳果糖长程组血氨与对照组、乳果糖短程组比较显著降低,差异有显著性意义。结论:乳果糖长程维持治疗能提高轻微型肝性脑病患者的生活质量,降低肝性脑病的发生率,降低血氨浓度;短程治疗改善生活质量的效果不明显。

Influence of lactulose on the cognitive level and quality of life in patients with minimal hepatic encephalopathy

BACKGROUND: The pathogenesis of hepatic encephalopathy is still not completely clear at present, and the theory of ammonia poisoning may be the most powerful, the mechanism for lactulose in decreasing ammonia is clearer, and there are many studies on hepatic encephalopathy treated by lactulose at home and aboard, but the comparative studies on the long-term and short-term treatment of lactulose and placebo control treatment are still in lack. OBJECTIVE: To given long-term and short-term treatment of lactulose to patients with minimal hepatic encephalopathy, and compare the effect on the quality of life (QOL) of the patients with minimal hepatic encephalopa thy. DESIGN: A case-control observation. SETTING: Department of Geriatrics, Guangzhou First People's Hospital. PARTICIPANTS: Sixty patients with minimal hepatic encephalopathy, who were abnormal in the number connection test (NCT), digital symbol test (DST) and/or evoked potential examination and cooperated with the treatment, were selected from the patients with cirrhosis treated in the De partment of Geriatrics of Guangzhou First People's Hospital between June 1998 and March 2002, and they were randomly divided into control group (n=20), short-term lactulose group (n=20) and long-term lactulose group (n=20). METHODS: All the patients were given vitamin B for 24 weeks, two tablets for each time, three times a day; besides, the patients in the short term lactulose group and long-term lactulose group were orally adminis tered with lactulose (15-90 mL per day) for 8 and 24 weeks respectively. They were assessed with WHOQOL-BREF at the end of 0, 8, 16 and 24 weeks respectively, the incidence rate of hepatic encephalopathy was observed, and the ammonia conc entration in blood was detected at the same period.MAIN OUTCOME MEASURES: The changes of QOL and ammonia concentration in blood during the treatment were observed.RESULTS: During the treatment, one case in the control group lost to the follow-up, one case in the short-term lactulose group died from traffic accident, and two cases in the long -term group quitted because they could not endure the side effect of diarrhea, and totally 56 cases finished the treatment and entered the analysis of results. ① The incidence rate of hepatic encephalopathy at 6 months was 40%(8/20), 30%(6/20), 5%(1/20) in the control group, short-term lactulose group and long-term lactulose group respectively, and it was significantly lower in the long-term lactulose group than in the control group and short-term lactulose group (P ＜ 0.05), but there was no significant difference between the short-term lactulose group and control group (P ＞ 0.05). ② At 8, 16 and 24 weeks after treatment,the score of environment in QOL had no significant difference among the control group, short-term lactulose group and long-term lactulose group (P ＞ 0.05), but there were significant differences in the scores of physiology,psychology and social relationship (P ＜ 0.05); At 8 weeks, there were more obvious differences in the long-term lactulose group and short-term lactulose group than in the control group, but no significant difference between the long and short-term lactulose groups; At 16 weeks, there were more obvious differences in the long-term lactulose group than in the short-term lactulose group and control group, but no significant difference between the short-term lactulose group and control group; At 24 weeks, the long-term lactulose group had more improvements than in the control group and short-term lactulose group. ③ At 16 and 24 weeks after treatment, the ammonia concentrations in blood were significantly decreased in the long-term lactulose group as compared with the control group and short-term lactulose group.CONCLUSION: The long-term treatment of lactulose can improve the QOL of patients with minimal hepatic encephalopathy, eventually reduce the incidence of hepatic encephalopathy and decrease the ammonia concentration in blood; However, the short-term treatment of lactulose could not.