正文:[摘要] 目的 探讨肠道去污剂联合培菲康对晚期肝硬化的肠屏障功能、内毒素及炎症因子水平变化,观察其对肝硬化并发症的发生率和死亡率的影响。 方法 选取我院127例晚期肝硬化患者,按治疗方法的不同将患者随机分为两组。对照组患者进行常规治疗,实验组患者在进行常规治疗的同时采用肠道去污剂联合培菲康治疗。比较并观察两组患者治疗6个月后肠粘膜通透性、肝脏Child-pugh评分、血液内毒素及炎症因子TNF-α、IL-6水平的变化情况,观察两组并发症及死亡率情况。结果 两组患者治疗前Child-Pugh评分、尿液L/M、TNF-α、IL-6、内毒素水平无显著差异(P>0.05)。随访6个月后,实验组患者Child-Pugh评分、尿液L/M、TNF-α、IL-6、内毒素水平低于对照组,差异有统计学意义(P<0.05)。实验组并发症发生率(13.85%)明显低于对照组(45.16%),差异有统计学意义(P<0.05)。实验组感染及肝性脑病的发生率显著低于对照组[(3/65,12/62,χ2=6.619,P<0.05),(2/65,9/62,χ2=5.249,P<0.05)],而上消化道出血、肝肾综合症在两组之间无统计学意义(P>0.05)。6个月后两组死亡率比较差异无统计学意义(4/62,2/65,χ2=0.228,P>0.05)。结论 采用肠道去污剂联合培菲康对晚期肝硬化患者进行治疗,能降低肝硬化患者肠粘膜的通透性,改善内毒素血症,减少炎性介质释放,且用药后可以降低晚期肝硬化患者感染及肝性脑病并发症的发生。
[关键词] 肠道去污剂;培菲康;肝硬化
Clinical effect of selective intestinal decontamination and bifico in patients of advanced cirrhosis
NI qianwen, TANG e, HUANG jiyin, AN min, SHEN manru, GAO zhenjun
Department of Gastroenterology, Qingpu Branch of Zhongshan Hospital Affiliated to Fu Dan University, Shanghai, 201799
[Abstract] Objective To observed the effect of intestinal detergents and bifico on changes of intestinal barrier function, endotoxin, inflammatory cytokine levels and incidence of complications and mortality in patients of advanced cirrhosis. Methods 127 patients with advanced cirrhosis were chosen, according to different methods of treatment, the patients were divided into two groups. The control group was given conventional therapy, the experimental group was treated with intestinal detergents, bifico and conventional therapy. The changes of intestinal permeability, Child-Pugh score, the levels of endotoxin and inflammatory cytokine TNF-α, IL-6 were compared after 6 months treatment between two groups. The complication and mortality of two groups were also observed. Results There was no significant difference before the treatment in Child-Pugh score, urine L/M, endotoxin and TNF-α,IL-6 levels between the two groups(P>0.05). After 6 months treatment, Child-Pugh, score, urine L/M, endotoxin and TNF-α, IL-6 levels, incidence of complications were significantly lower in experimental group(13.85%) than those in the control group(45.16%), the difference had significant statistics(P<0.05). The complications of infection and hepatic encephalopathy were lower in experimental than those in control group[(3/65,12/62,χ2=6.619,P<0.05),(2/65,9/62,χ2=5.249,P<0.05)]. There was no significant difference in the incidence of upper gastrointestinal bleeding ,liver and kidney syndrome(P>0.05). There was no difference in mortality between the two groups(P>0.05). Conclusion The treatment of intestinal detergent and bifico in patients with advanced cirrhosis can reduce intestinal mucosal permeability, endotoxemia and the release of inflammatory mediators, which can also reduce the incidence of infection and hepatic encephalophathy in cirrhosis patients.
[Key words] intestinal detergents; bifico; liver cirrhosis
晚期患者肠道屏障功能障碍引起肠内细菌易位及肠源性内毒素血症是并发细菌性腹膜炎、肝性脑病等多种并发症的重要原因1。去污又称选择性清洁肠道措施2(selective decontamination of digestive tract, SDD),与微生态制剂均为常见的生态疗法。采用SDD联合微生态制剂可清除肠道杂菌,有效降低肝硬化患者体内内毒素水平,从而对预防肝硬化并发症的发生产生积极影响3。本资料通过对照分析肝硬化失代偿期患者肠道去污联合微生态制剂治疗前后肠粘膜屏障功能、血清内毒素水平及炎性细胞因子、肝脏储备功能变化,探讨肠道去污剂联合微生态制剂治疗晚期肝硬化的有效性和安全性,为改善晚期肝硬化患者预后提供理论依据。
1 资料与方法
临床资料
选取2016年1月-2017年1月在我院进行治疗的127例肝硬化患者,采用随机排列表将患者随机分为实验组和对照组。对照组62例患者中女32例,男30例,年龄47-85岁,平均(65.39±10.77)岁,其中慢性酒精中毒3例、血吸虫肝硬化27例、乙肝后肝硬化30例、自身免疫性肝病2例,平均病程(9.08±4.37)年。实验组65例患者中女27例,男38例,年龄46-82岁,平均年龄(68.46±9.70)岁,其中慢性酒精中毒2例、血吸虫肝硬化30例、乙肝后肝硬化32例、自身免疫性肝病1例,平均病程(8.73±4.15)年。纳入标准:诊断符合2013年第3版《肝脏病学》中的肝硬化诊断标准,有病因根据、肝脏质地改变、肝脏储备功能受损、门静脉高压症表现、影响学检查依据。肝肾综合症、自发性腹膜炎、诊断参考2010年欧洲肝病学会《肝硬化腹水、自发性腹膜炎及肝肾综合症诊疗指南》4。排除标准:肝硬化合并有肝癌者,有严重心、脑、肺、肾等基础疾病和代谢疾病,不能按时随访者,有相关药物过敏史者。两组年龄、性别构成、病程、病因、肝功能Child-Pugh分级比较差异均无统计学意义(P>0.05),具有可比性。
方法
对照组患者进行常规治疗,包括卧床休息,补充维生素和热量,控制水和盐的摄入,利尿、保肝、输注白蛋白和新鲜血浆,实验组在采用对照组治疗方法的基础上,口服肠道去污剂:用30ml浓度为0.9%的氯化钠注射液将0.4g诺氟沙星,420mg双歧杆菌三联菌株(上海信谊制药有限公司),10g乳果糖混合,制成肠道去污剂,每天三次,口服,每次用量10ml。在随访过程中,患者出现严重并发症时作相应紧急治疗,病情稳定后继续方案治疗。
观察指标
比较观察两组患者治疗6个月后肠粘膜通透性、血清内毒素水平、TNF-α、IL-6水平变化,比较随访6个月前后对照组和研究组并发症和死亡率的差异。(1)肠粘膜通透性:在患者空腹超过8h以后,给予患者口服1包乳果糖,6h后取患者尿液进行乳果糖/甘露醇排出比(L/M)测定; (2)TNF-α、IL-6测定:应用ELISA双抗体夹心法,试剂由深圳晶美生物工程有限公司提供,按说明书操作,以ng/L表示;标本采集:清晨空腹采血样本,用无致热原注射器于肘静脉采血5ml,标本于低温离心 5~10min,留取血浆并分装,-7O℃保存待检(3)采用鲎试验检测血浆内毒素 (鲎试剂由上海伊华临床科技公司提供)。结果以Eu/L表示。
统计学处理
统计分析时采用SPSS 17.0软件分析,计量资料以均数±标准差表示,计量资料采用t检验,计数资料采用卡方检验,以P<0.05为差异有统计学意义。
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