乳果糖预防肝硬化消化道出血后诱发肝性脑病的meta分析

目的探讨乳果糖制剂用于预防肝硬化消化道出血后诱发肝性脑病发生的疗效评价。方法计算机检索PubMed、Wiley、The Cochrane Central Register of Controlled Trials外文数据库及CNKI中国期刊全文数据库、万方数字化期刊全文数据库、维普中文科技期刊全文数据库中文数据库中有关乳果糖预防肝硬化消化道出血后诱发肝性脑病发生的临床随机对照试验,采用RevMan5.0软件对入选试验进行Meta分析。结果共5项随机对照试验符合入选标准,包括318例患者。Meta分析结果显示:乳果糖制剂可以明显降低肝硬化消化道出血病人肝性脑病的发生率(RR=0.20,95%CI:0.10~0.40,P0.000 01),有效降低血氨水平(WMD=-9.10,95%CI:-11.48~-6.73,P0.000 01),缩短数字连接试验所需的反应时间(WMD=-14.48,95%CI:-20.08~-9.60,P0.000 01)。结论乳果糖制剂可改善肝硬化消化道出血患者部分指标,对预防肝硬化消化道出血患者肝性脑病的发生有一定疗效。     

益生菌制剂治疗肝硬化的meta分析

背景:肠道菌群失调在肝硬化及其并发症的发生中起重要作用。近年来益生菌制剂在肝硬化治疗中的应用引起了广泛关注。目的:评价益生菌制剂治疗肝硬化的疗效。方法:检索PubMed、Springer Link、Wiley Online Library、MEDLINE、Web of Science、The Cochrane Library以及CNKI、维普、万方数据库,选取关于益生菌制剂治疗肝硬化的随机对照试验(RCTs),应用RevMan 5.1软件进行meta分析。二分类变量和连续变量分别采用相对危险度(RR)和加权均数差(WMD)或标准化均数差(SMD)进行评估。结果:共27项RCTs满足纳入和排除标准。与对照组相比,益生菌制剂可显著降低肝硬化患者的外周血ALT(WMD=15.08,95%CI:6.67~23.49,P=0.000 4)、AST(WMD=5.24,95%CI:0.75~9.73,P=0.02)水平和血氨(SMD=0.35,95%CI:0.16~0.54,P=0.000 3)、内毒素(SMD=0.75,95%CI:0.55~0.96,P0.000 01)含量,升高血清白蛋白水平(WMD=0.97,95%CI:0.47~1.48,P=0.000 1),缩短数字连接试验(NCT)反应时间(WMD=24.03,95%CI:4.06~44.00,P=0.02),降低肝性脑病(HE)(RR=0.48,95%CI:0.26~0.89,P=0.02)和自发性细菌性腹膜炎(SBP)(RR=0.53,95%CI:0.38~0.74,P=0.000 2)发生率。对肝硬化合并HE的亚组分析显示,益生菌制剂可显著降低HE患者的血氨和内毒素含量。结论:益生菌制剂可明显改善肝硬化患者的临床症状和生化指标,降低HE和SBP的发生风险,对肝硬化合并HE有明显治疗作用。     

微生态制剂治疗肝硬化的Meta分析

目的系统评价微生态制剂治疗肝硬化的有效性。方法计算机检索PubMed、Embase、Cochrane Library以及中国期刊全文数据库、维普、万方数据库,全面收集关于微生态制剂治疗肝硬化的随机对照试验,筛选后的文献应用Rev Man5.3软件进行Meta分析,其中二分类变量采用率差(RD)及其95%可信区间(95%CI)作为效应量;连续性变量若测量单位一致则采用加权均数差(WMD),测量单位不一致采用标准化均数差(SMD)及其95%CI进行评估。发表偏倚采用漏斗图进行分析。结果纳入符合标准的文献18篇,共1411例肝硬化患者,其中治疗组726例,对照组685例。与对照组相比,微生态制剂治疗可显著提高临床总体有效率(RD=0.28,95%CI:0.22~0.34,P0.001);亦可以明显改善肝功能生化指标:ALT(SMD=-0.90,95%CI:-1.14~-0.66,P0.001)、TBil(WMD=-15.99,95%CI:-26.42~-5.57,P0.001)、Alb(SMD=0.66,95%CI:0.40~0.93,P0.001),降低内毒素(SMD=-1.13,95%CI:-2.11~-0.15,P0.001)及血氨水平(WMD=-15.86,95%CI:-21.54~-10.18,P0.001)。结论微生态制剂可明显改善肝硬化患者的肝功能,有效抑制肝硬化进展,降低肝性脑病等并发症的发生风险,提高临床总有效率,且耐受性较好。     

益生菌对轻微肝性脑病疗效的Meta分析

目的 系统评价益生菌治疗轻微肝性脑病（minimal hepatic encephalopathy,MHE）的有效性。方法 计算机检索PubMed、EMbase、Cochrane Central Register of Controlled Trials、中国知网、万方、中国生物医学文献数据库和维普数据库,检索益生菌制剂治疗MHE的随机对照试验（randomized controlled trial,RCT）,检索时限均为建库至2020年7月26日。检索美国临床试验注册平台（ClinicalTrials.gov）进行文献补充。由2名研究人员独立筛选文献、提取数据、评价纳入研究的偏倚风险,采用RevMan 5.3进行Meta分析。结果 共纳入13篇RCT,Meta分析表明益生菌治疗组在降低血氨水平（SMD=-0.79,95%CI:-1.20～-0.37,P=0.0002）、缩短数字连接试验-A型（number connection test-type A,NCT-A）反应时间（MD=-16.31,95%CI:-22.09～-10.53,P <0.001）、降低显性肝性脑病发生率（R...     

乳果糖联合益生菌治疗轻微型肝性脑病的Meta分析

目的系统评价乳果糖联合益生菌治疗轻微型肝性脑病(minimal hepatic encephalopathy,MHE)的疗效和安全性。方法系统检索PubMed、Embase、Web of Science、Cochrane Library等英文数据库,以及CBM、CNKI、万方、维普等中文数据库,检索2020年1月31日前发表的乳果糖联合益生菌治疗在肝硬化或慢性肝病基础上发生MHE的随机对照试验;2名研究者单独按照纳入及排除标准进行文献筛选、质量评价、数据提取;最后采用RevMan 5.3软件进行Meta分析。结果最终纳入8篇文献,受试者共计545例。Meta分析结果显示:乳果糖联合益生菌和单用乳果糖相比,显性肝性脑病(overt hepatic encephalopathy,OHE)进展率(RR=0.15,95%CI:0.05～0.51,P=0.002)、血氨(MD=-14.37,95%CI:-17.35～-11.38,P0.0001)、数字连接试验(MD=-18.56,95%CI:-28.29～-8.82,P=0.0002)差异有统计学意义,肝功能ALT(MD=-0.74,95%CI:-8.74～7.26,P=0.86)、AST(MD=-4.20,95%CI:-13.29～4.88,P=0.36)、不良反应发生率(RR=0.47,95%CI:0.13～1.64,P=0.23)差异无统计学意义(P0.05)。结论现有证据表明,与单用乳果糖相比,联合使用益生菌可有效降低MHE患者血氨水平,减少MHE向OHE进展,临床效果值得推广。     

益生菌类制剂治疗非酒精性脂肪性肝病疗效评价

目的系统评价益生菌制剂对非酒精性脂肪性肝病(NAFLD)的疗效。方法检索2014年5月之前在Pub Med、Springer Link、CNKI中文期刊全文数据库、维普中文科技期刊数据库网及万方数据库中发表的文献,选取关于益生菌制剂治疗NAFLD的随机对照试验,由2名研究者独立对文献进行质量评价和数据提取,应用Rev Man5.1软件进行Meta分析。连续性变量计量单位相同采用加权均数差(WMD)进行评估。结果共纳入8项符合标准的随机对照试验相关文献,NAFLD患者共543。Meta分析显示:与对照组相比,益生菌制剂能明显降低NAFLD患者的ALT(WMD=17.74,95%CI:12.23~23.14,P<0.000 01)、AST(WMD=9.01,95%CI:8.13~9.89,P<0.000 01)、GGT(WMD=16.48,95%CI:1.91~31.05,P=0.03)、CHO(WMD=0.24,95%CI:0.16~0.31,P<0.000 01)和TG(WMD=0.29,95%CI:0.13~0.45,P=0.000 4)水平,不能改善BMI(WMD=0.04,95%CI:-0.48~0.57,P=0.87)。结论益生菌制剂可降低NAFLD患者ALT、AST、GGT、CHO和TG水平,促进肝功能的恢复,但对患者的BMI无改善作用。     

法舒地尔辅助治疗慢性心力衰竭患者临床效果的Meta分析

目的运用Meta分析方法评价法舒地尔辅助治疗慢性心力衰竭患者的临床效果。方法计算机检索中国期刊全文数据库(CNKI)、中文科技期刊全文数据库(VIP)、万方数字化期刊全文库、Pubmed和Cochrane library,对纳入的随机对照试验文献进行质量评价,并采用Rev Man 5.2软件进行Meta分析。结果共纳入15篇随机对照试验,共1353例患者。Meta分析结果显示,与常规治疗组相比,法舒地尔加用常规治疗可有效提高慢性心力衰竭患者的临床疗效(RR=1.16,95%CI:1.10~1.23,P0.01),延长6分钟步行试验距离(WMD=49.02,95%CI:42.85~55.2,P0.01),提升左室射血分数(WMD=0.06,95%CI:0.05~0.07,P0.01),以及缩小左室舒张末期内径(WMD=-3.01,95%CI:-4.18~-1.84,P0.01)和左心室收缩末期内径(WMD=-3.74,95%CI:-4.88~-2.60,P0.01)。结论法舒地尔辅助治疗慢性心力衰竭患者可改善心功能,并能抑制左室重塑,提高临床疗效,但仍需开展高质量的药物临床试验。     

益生菌联合美沙拉嗪治疗溃疡性结肠炎疗效的Meta分析

目的系统评价益生菌联合美沙拉嗪诱导活动期溃疡性结肠炎(UC)缓解的有效性,为临床治疗提供循证参考。方法检索外文Pubmed、Embase、Cochrane图书馆(至2018年12月)和中国期刊全文数据库、中国科技期刊数据库(维普)、中国生物医学文献数据库、万方数字化期刊全文数据库。纳入符合条件的益生菌联合美沙拉嗪与美沙拉嗪治疗活动期UC的随机对照试验(RCT)。采用Jadad量表评价文献质量,应用RevMan5. 3软件对数据进行处理。结果本研究共纳入20个随机对照试验。益生菌联合美沙拉嗪在诱导活动期UC缓解方面优于美沙拉嗪(OR=3. 50; 95%CI:2. 44～5. 01; P 0. 0001)。益生菌联合美沙拉嗪在预防UC复发方面优于美沙拉嗪(OR=0. 32; 95%CI:0. 16～0. 68; P=0. 003)。益生菌联合美沙拉嗪与单独应用美沙拉嗪其不良反应发生率无明显差异(OR=0. 70; 95%CI:0. 41～1. 18; P=0. 18);益生菌联合美沙拉嗪治疗的患者其内镜评分显著低于单独美沙拉嗪治疗组(WMD=-0. 61; 95%CI:-0. 74～-0. 48),异质性检验修正后,(WMD=-0. 73; 95%CI:-0. 88～-0. 58);益生菌联合美沙拉嗪治疗的患者其C-反应蛋白(CRP)水平显著低于单独美沙拉嗪治疗组(WMD=-2. 93; 95%CI:-3. 39～-2. 48),异质性检验修正后,(WMD=-2. 66; 95%CI:-3. 17～-2. 16);益生菌联合美沙拉嗪治疗的患者其白细胞介素-8(IL-8)水平显著低于单独美沙拉嗪治疗组(WMD=-6. 06; 95%CI:-7. 10～-5. 02),异质性检验修正后,(WMD=-3. 81; 95%CI:-4. 92～-2. 70);益生菌联合美沙拉嗪治疗的患者其肿瘤坏死因子-α(TNF-α)水平显著低于单独美沙拉嗪治疗组(WMD=-0. 38; 95%CI:-0. 46～-0. 30),异质性检验修正后,(WMD=-1. 32; 95%CI:-2. 59～-0. 05);益生菌联合美沙拉嗪治疗的患者其超氧化物歧化酶(SOD)水平显著高于单独美沙拉嗪治疗组(WMD=0. 18; 95%CI:0. 16～0. 21),异质性检验修正后,WMD分别为0. 10,0. 38; 95%CI分析为0. 07～0. 13,0. 33～0. 42。结论益生菌联合美沙拉嗪可有效诱导活动期UC缓解,用药安全,预防UC复发,并显著降低患者血清炎性指标CRP、IL-8、TNF-α水平及增强抗氧化能力。     

乳果糖预防肝硬化消化道出血后肝性脑病疗效的系统评价

目的:评价乳果糖预防肝硬化消化道出血后肝性脑病的疗效.方法:检索1990-01/2015-08 Medline、Embase、SCI、CBM以及Cochrane图书馆数据库,不限语种纳入所有关于乳果糖预防消化道出血后肝性脑病的随机对照试验(randomized controlled trials,RCT)文献,对搜索到的RCT以及参考文献进行二次筛选,对纳入的研究进行质量评价,采用Rev Man软件进行Meta分析.结果:共有11篇R C T文献符合纳入标准.Meta分析结果显示,增加乳果糖治疗可以减少肝硬化上消化道出血后肝性脑病的发生率(RR=0.24,95%CI:0.16-0.35,P0.00001),减少SHE的发生率(RR=0.15,95%CI:0.06-0.38,P0.0001),缩短数字连接试验时间(WMD=-12.55,95%CI:-17.23--7.87,P0.00001),降低血氨浓度(W M D=-6.44,95%CI:-8.26--4.61,P0.00001).结论:乳果糖可以降低肝硬化合并消化道出血时肝性脑病以及SHE的发生率,降低血氨水平、改善数字连接试验(number connection test,NCT)时间,不良反应率低,可以推荐用来预防肝硬化消化道出血患者肝性脑病的发生.目前需要大样本量、多中心、高质量的RCT来支持这一循证医学结论.     

温阳活血解毒方治疗急性冠脉综合征临床疗效的Meta分析

目的系统评价温阳活血解毒方治疗急性冠脉综合征(ACS)的临床疗效及安全性。方法检索中文数据库包括中国生物医学文献数据库、中国期刊全文数据库、维普资讯中文期刊平台及万方期刊数据库;外文数据库包括PubMed、EMbase及Cochrane Library。筛选合格研究,进行文献质量评估,将符合条件的文献采用RevMan5.3软件进行异质性检验、Meta分析、敏感性分析等。结果共纳入10篇文献,Meta分析结果提示温阳活血解毒方联合西药可降低ACS病人中医证候评分[WMD=-4.12,95%CI(-5.19,-3.05),P<0.00001],降低超敏C反应蛋白[SMD=-1.87,95%CI(-2.81,-0.927),P=0.0001]和白细胞计数[WMD=-1.42,95%CI(-2.13,-0.72),P<0.0001]水平,提高临床总有效率[RR=1.22,95%CI(1.13,1.31),P<0.00001]。结论温阳活血解毒方联合西药较单纯常规治疗ACS,可提高病人临床疗效,改善症状,减轻炎症反应。     

Systematic review and meta-analysis of randomized trials on probiotics for hepatic encephalopathy

Aim: The objective of this systematic review and meta‐analysis was to assess the efficacy of probiotics and synbiotics in patients with hepatic encephalopathy. Methods: Eligible trials were identified by searching electronic databases including MEDLINE, the Cochrane Library, Science Citation Index and Embase, abstract proceedings, reference lists and ongoing trial registers until 13 October 2010. We included randomized controlled trials comparing probiotics and synbiotics with no intervention, placebo or lactulose in patients with hepatic encephalopathy. The primary outcome measure was improvement in hepatic encephalopathy. Results were expressed as risk rates (RR) with confidence intervals (CI) and intertrial heterogeneity as I². Results: Seven trials with a total of 393 patients were analyzed. Compared to placebo or lactulose, treatment with probiotics or synbiotics significantly improved hepatic encephalopathy (RR = 1.40, 95% CI = 1.05–1.86, I² = 5%). Probiotics decreased arterial ammonia (weighted mean difference 15.95; 95% CI = 26.72–3.28; I² = 68%), but not venous ammonia (weighted mean difference 5.23; 95% CI = 21.77–11.30; I² = 89%). Treatment with probiotics or synbiotics did not significantly affect the psychometric tests. Overall adverse events were reported in four trials with no difference between probiotics and placebo groups (RR = 0.32, 95% CI = 0.04–2.57; I² = 59%). Regression analysis showed evidence of small‐study effects. Conclusion: The present meta‐analysis suggests that probiotics may be an effective treatment of hepatic encephalopathy, though rigorous evaluation in standardized, randomized, clinical trial with clinically relevant outcomes is still needed.     

Chinese guidelines on management of hepatic encephalopathy in cirrhosis

The Chinese Society of Hepatology developed the current guidelines on the management of hepatic encephalopathy in cirrhosis based on the published evidence and the panelists' consensus. The guidelines provided recommendations for the diagnosis and management of hepatic encephalopathy(HE) including minimal hepatic encephalopathy(MHE) and overt hepatic encephalopathy, emphasizing the importance on screening MHE in patients with end-stage liver diseases. The guidelines emphasized that early identification and timely treatment are the key to improve the prognosis of HE. The principles of treatment include prompt removal of the cause, recovery of acute neuropsychiatric abnormalities to baseline status, primary prevention, and secondary prevention as soon as possible.     

Disaccharides in the treatment of hepatic encephalopathy

Management of hepatic encephalopathy (HE) primarily involves avoidance of precipitating factors and administration of various ammonia-lowering therapies such as nonabsorbable disaccharides and antimicrobial agents like rifaximin. The nonabsorbable disaccharides which include lactulose and lactitol are considered the first-line therapy for the treatment of HE and minimal hepatic encephalopathy (MHE). Lactulose significantly improves cognitive function and health-related quality of life in patients with MHE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects. Lactulose has also shown to be effective in primary and secondary prophylaxis of HE. Disaccharides were found to be comparable to rifaximin in recent systemic reviews in the treatment of HE however conclusion was based on inclusion of some poor quality trials. Combination therapy of disaccharides either with rifaximin, L-ornithine L-aspartate,probiotics for the treatment of HE needs further validation in large studies.     

替比夫定治疗慢性乙型肝炎疗效的系统评价

目的:系统评价替比夫定(LDT)治疗慢性乙型肝炎(CHB)的治疗效果.方法:应用Cochrane系统评价方法计算机检索Cochrane Library(2009年第3期)、PubMed(1966-2009.9)、EMBASE(1974-2009.9)、中国生物医学数据库(CBM,1978-2009.9)、中国期刊全文数据库(CNKI,1979-2009.9)和维普数据库(VIP,1989-2009.9),同时在临床试验注册网站及Google搜索引擎进行检索,并追查纳入研究参考文献,收集以LDT治疗CHB的所有随机对照试验(RCT)和交叉试验.根据Cochrane协作网推荐的风险评估工具进行风险偏倚评估,用RevMan5.0软件进行统计学分析.结果:最终纳入10个RCTs,共4037例患者.7篇LDT对比拉米夫定(LAM)的研究结果显示,对于HBeAg阳性患者,LDT组较LAM组更有效提高血清HBVDNA检测不到率(RR=1.50,95%CI:1.38-1.64)、ALT复常率(RR=1.10,95%CI:1.05-1.16)、HBeAg转阴率(RR=1.23,95%CI:1.08-1.40)和HBeAg血清转...     

Minimal hepatic encephalopathy: time to recognise and treat

Minimal hepatic encephalopathy represents a part of the spectrum of hepatic encephalopathy and is the mildest form. While patients with hepatic encephalopathy have impaired intellectual functioning, personality changes, altered levels of consciousness, and neuromuscular dysfunction, patients with minimal hepatic encephalopathy have no recognisable clinical symptoms of hepatic encephalopathy but have mild cognitive and psychomotor deficits. The prevalence of minimal hepatic encephalopathy has been reported to vary between 30% and 84% in patients with liver cirrhosis and is higher in patients with poor liver function. The diagnosis is usually made by neuropsychological and/or neurophysiological testing in cirrhotic patients who are otherwise normal on neurological examination. Minimal hepatic encephalopathy is a clinically significant disorder that impairs the health-related quality of life, predicts the development of overt encephalopathy and is probably associated with a poor prognosis. Thus screening all patients with cirrhosis for minimal hepatic encephalopathy using psychometric testing is recommended. Pharmacologic therapy is recommended for patients diagnosed with minimal hepatic encephalopathy. The pathogenesis of minimal hepatic encephalopathy is considered similar to that of overt hepatic encephalopathy and ammonia plays a key role. Thus ammonia lowering agents such as lactulose, L-ornithine and L-aspartate that have good safety profiles are recommended. Future studies will better define the role of probiotics, levocarnitine and sodium benzoate.     

Probiotics and liver disease

Modulation of intestinal flora through the use of probiotics is an emerging therapeutic strategy in the management of chronic liver diseases. This article focuses on the pathophysiologic basis for using probiotics in liver disease and reviews the existing literature on the subject. The role of probiotics is examined in the following areas: a) prevention of infection, b) the hyperdynamic circulatory state of cirrhosis, c) hepatic encephalopathy, d) liver function, and e) nonalcoholic fatty liver disease.     

隐匿性肝性脑病的诊疗进展

隐匿性肝性脑病(minimal hepatic encephalopa-thy,MHE)又称亚临床肝性脑病(subclinicalhepatic encephalopathy,SHE),是慢性肝病和肝硬化最常见的严重并发症,是一种具有渐进性、可逆性的神经精神病学异常和运动功能失调特点的疾病.尽管其发病机制仍未明确,血清和中枢神经系统(central nervoussystem,CNS)血氨升高仍被认为是肝性脑病(hepatic encephalopathy,HE)的致病机制和治疗核心,并受血脑屏障改变、神经递质紊乱、氨基丁酸和苯二氮异常等因素影响.因此明确其诱发因素是HE治疗的关键.治疗药物包括抗生素、二糖类、益生菌、门冬氨酸鸟氨酸(L-ornithine-L-aspartate,LOLA)、苯甲/苯乙酸盐等.因此,对MHE的发病机制、临床诊断和治疗研究进展进行归纳,为临床诊疗提供前沿性、系统性信息,具有重要意义.     

微生态制剂联合肠内营养治疗肝性脑病的临床研究

[目的]观察微生态制剂联合肠内营养治疗对肝性脑病患者血清内毒素、肿瘤坏死因子α(TNF-α)、白细胞介素18(IL-18)、血氨水平及全身营养状态的影响。[方法]选取60例肝性脑病患者,随机分为3组,在常规保肝利尿等基础上,3组分别予口服培菲康加肠内营养、单纯口服培菲康、单纯静脉营养,疗程均为2周。分别检测治疗前和治疗后第7天、第14天血清内毒素、TNF-α、IL-18、血氨及白蛋白的水平。[结果]与治疗前相比,培菲康联合肠内营养治疗能明显下调血清内毒素、TNF-α、IL-18及血氨的水平,明显升高血浆白蛋白的水平,与单用培菲康及单用静脉营养治疗相比差异有统计学意义(P0.05)。[结论]微生态制剂联合肠内营养治疗能有效清除血氨、降低内毒素血症、保护肠黏膜屏障及改善机体的营养状态,是临床治疗肝性脑病的一条安全而高效的途径。     

Diagnosis and Prognostic Significance of Minimal Hepatic Encephalopathy in Patients with Cirrhosis of Liver

Background and Aims  

Minimal hepatic encephalopathy is the mildest form of the spectrum of hepatic encephalopathy (HE) that impairs health-related quality of life. We assessed (1) the usefulness of psychometric hepatic encephalopathy score and critical flicker frequency for the diagnosis of minimal hepatic encephalopathy, and (2) prognostic significance of minimal hepatic encephalopathy.