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...     

益生菌对轻微型肝性脑病患者显性肝性脑病发生率影响的Meta分析

目的 评价使用益生菌干预对轻微型肝性脑病患者显性肝性脑病发生率的影响。方法 本研究根据PRISMA指南完成,PROSPERO注册号为CRD42022303995。检索PubMed、Web of Science、Cochrane Library、知网、万方数据库,收集建库至2021年11月有关益生菌干预治疗轻微型肝性脑病的研究。用RevMan 5.4进行Meta分析,不能合并的数据采用描述性分析。选择危险比(RR)和95%CI作为汇总指标。结果 共纳入6篇文献,均为随机对照研究,共404例轻微型肝性脑病患者。结果表明益生菌干预可使轻微型肝性脑病患者显性肝性脑病的发生率降低54%(RR=0.46,95%CI:0.26～0.81,P=0.007),并且能增加轻微型肝性脑病患者疾病的逆转率(RR=4.94,95%CI:2.82～8.66,P<0.000 01)。结论 益生菌能够降低轻微型肝性脑病患者显性肝性脑病的发生率,增加轻微型肝性脑病的逆转率,对轻微型肝性脑病患者预防显性肝性脑病的发生具有积极意义,为益生菌治疗轻微型肝性脑病提供了新的证据。     

轻微型肝性脑病诊断与治疗

轻微型肝性脑病(MHE)是指部分肝硬化患者无明显肝性脑病(HE)临床表现,但通过精细的神经心理或神经生理学检查可发现患者存在认知功能障碍.MHE也可发生于门体分流患者.基于West Haven分期,HE临床上分为Ⅰ～Ⅳ期.近期有学者将MHE和Ⅰ期HE统称为隐性肝性脑病(covert HE),相应的显性肝性脑病(overt HE,OHE)则为Ⅱ～Ⅳ期HE[1,2].     

轻微型肝性脑病流行病学与发病机制研究进展

轻微型肝性脑病是肝性脑病的一种特殊类型。近年来,我国学者对本病的流行病学、发病机制及预后方面的研究获得一定的进展,本文将作一介绍。     

轻微性肝性脑病的诊断进展

肝性脑病（HE）是肝硬化常见的严重并发症。一旦发生肝性脑病,提示慢性肝病患者预后不佳。轻微性肝性脑病（MHE）是HE的早期阶段,无明显症状,但在神经心理学和/或神经生理学测试中表现出异常的结果。MHE影响患者的生活质量、就业及驾驶能力并具有进展到显性肝性脑病的高风险。应探讨诊断MHE的各种方法,加强临床医生在日常诊疗活...     

轻微肝性脑病的研究进展

早在1970年,Zeegen等观察了51名门-体静脉分流术后的无神经或精神方面异常的肝硬化患者,采用神经心理学检测却发现62%的病例结果不正常。1978年命名亚临床型肝性脑病（SHE）以来就存在争议,认为SHE应为肝性脑病的轻微型,故在1998年维也纳召开的第11届世界胃肠病大会上将SHE更名为轻微肝性脑病（MHE）。     

轻微型肝性脑病的流行状况

轻微型肝性脑病（minimal hepatic encephalopathy，MHE）也称为亚临床肝性脑病（subclinical hepatic encephalopathy，SHE），是指由严重肝病引起的，临床缺乏肝性脑病的表现，精神和神经功能常规检查正常，按4级分类法不属于肝性脑病范围，而用严格的智力心理学测验和（或）脑诱发电位检查则表现异常。它可发生于各种急慢性肝病患者，主要见于各种类型的肝硬化（常见的有病毒性肝硬化、血吸虫病性肝硬化、酒精性肝硬化等）及各种门体分流术等。     

斯特鲁普测试对肝硬化合并轻微型肝性脑病的诊断价值

目的:评估斯特鲁普(Stroop)测试对肝硬化合并轻微型肝性脑病(MHE)的诊断价值，初步探究Stroop测试联合其他神经心理学测试对MHE的诊断效能。方法:选取185例肝硬化患者作为肝硬化组，277例健康体检者作为健康组。两组人群均完成数字连接试验A(NCT-A)和数字连接试验B(NCT-B),肝硬化组患者还需完成Stroop测试和动物命名测试(ANT)。以NCT-A、NCT-B和ANT均异常作为MHE的诊断标准，将肝硬化组患者分为单纯肝硬化组和肝硬化MHE组。利用ROC曲线分别分析单用Stroop测试、Stroop测试联合NCT-A/NCT-B/ANT诊断策略对MHE的诊断价值，建立交叉表评价上述不同诊断方法对MHE的诊断效能。结果:185例肝硬化患者中有58例(31.35%)诊断为MHE。ROC曲线分析显示，Stroop测试指标中的Off time+On time取诊断临界值212.199 s时可以最好地识别MHE,AUC、敏感性和特异性分别为0.762(P<0.05)、79.3%和61.4%;Stroop测试联合NCT-A/NCT-B/ANT的不同序列试验方法对诊断MHE...     

肝硬化患者轻微肝性脑病临床相关危险因素分析

目的评估肝硬化人群中轻微型肝性脑病（MHE）发生的相关因素.方法在121例肝硬化患者,分别进行心理肝性脑病得分（PHES）和临界闪烁频率（CFF）测定,并评估肝功能分级状态.结果在121例肝硬化患者中,检出MHE者70例（57.9%）.性别、受教育程度、肝病病因、肝功能Child-Pugh分级、血浆氨浓度等因素对肝硬化患者发生MHE无统计学意义（P〉0.05）;经Logistic多因素回归分析,仅发现年龄为MHE发生的危险因素（P=0.041, OR=1.035）,而MHE发生与性别、教育程度、肝病病因、肝功能Child-Pugh分级和血浆氨浓度无关（P〉0.05）.结论在肝硬化患者中MHE发生率较高,年龄增长是肝硬化患者发生MHE的危险因素.     

轻微肝性脑病的研究进展

轻微肝性脑病(minimal hepatic encephalopathy,MHE)是并发于各种类型的肝硬化及各种门体分流术患者出现认知功能紊乱的表现,其发病机制仍不清楚,目前所公认的是经典的氨中毒学说。由于MHE缺乏典型的临床表现,只能通过神经心理测试和神经生理测试发现,其发病率已上升至30%～84%,MHE可对患者的日常生活造成影响,很可能发展为症状性肝性脑病(OHE),病死率极高,目前有研究表明益生菌可明显改善MHE症状,防止MHE发展为症状性肝性脑病(OHE)。本文就MHE的流行病学调查、发病机制、临床表现、诊断方法和其与益生菌的关系作一综述。     

Comparison of probiotics and lactulose in the treatment of minimal hepatic encephalopathy in rats

AIM: To compare the efficacy of probiotic preparation Golden Bifid and lactulose on rat experimental model of minimal hepatic encephalopathy (MHE) induced by thioactamide (TAA). METHODS: MHE was induced by intraperitoneal injection of TAA (200 mg/kg) every 24 h for two consecutive days. Thirty-six male MHE models were then randomly divided into 3 groups: TAA group (n = 12) received tap water ad libitum only; lactulose group (n = 12) and probiotics group (n = 12) were gavaged, respectively with 8 mL/kg of lactulose and 1.5 g/kg of probiotic preparation Golden Bifid (highly concentrated combination of probiotic) dissolved in 2 ml of normal saline, once a day for 8 d (from the 5th d before the experiment to the 3rd d of the experiment). The latency of brainstem auditory evoked potentials (BAEP) I was used as an objective index of MHE. The incidence of MHE, the level of serum endotoxin, ammonia, liver function and histological grade of hepatic injury of rats were examined individually. RESULTS: There were no overt HE and rat deaths in 3 groups. The incidence of MHE, the levels of blood ammonia and endotoxin in TAA group, which were 83.3% (10/12), 168.33±15.44 mg/dL and 0.36±0.04 EU/mL, respectively, were significantly higher than those in lactulose group, which were 33.3% (4/12), 110.25±7.39 mg/dL and 0.19±0.02 EU/mL, and probiotics group, which were 33.3% (4/12), 108.58±10.24 mg/dL and 0.13±0.03 EU/mL respectively (P <0.001). It showed that either probiotics or lactulose could significantly lower the level of hyperammonemia and hyper-endotoxemia, lighten centrolobular necrotic areas as well as inflammatory reaction in the liver of rats, normalize the latency of BAEP, and decrease the incidence of MHE. However, no significant differences were observed between these two groups (P>0.05). CONCLUSION: Probiotic compound Golden Bifid is at least as useful as lactulose for the prevention and treatment of MHE. Probiotic therapy may be a safe, natural, well-tolerated therapy appropriate for the long-term treatment of MHE.     

Effect of probiotic treatment on cirrhotic patients with minimal hepatic encephalopathy: A meta-analysis

Background: Minimal hepatic encephalopathy(MHE) is an early and reversible form of hepatic encephalopathy. The documentations on the treatment with probiotics are inconsistent. The present meta-analysis was to verify the role of probiotics in the treatment of cirrhotic patients with MHE.Data sources: Seven electronic databases were searched for relevant randomized controlled trials(RCTs)published until July 2015. The effects of probiotics on serum ammonia, endotoxin, and MHE were evaluated.Results: A total of 14 RCTs(combined n = 1132) were included in the meta-analysis. When probiotics were compared to placebo or no treatment, probiotics were more likely to reduce values in the number connection test(NCT; week 4: MD =-30.25, 95% CI:-49.85 to-10.66), improve MHE(week 4: OR = 0.18,95% CI: 0.07 to 0.47; week 12: OR = 0.15, 95% CI: 0.07 to 0.32), and prevent overt HE progression(week4: OR = 0.22, 95% CI: 0.07 to 0.67) in patients with liver cirrhosis. When probiotics was compared to lactulose, probiotics tended to reduce serum ammonia levels(week 4: MD =-0.33 μmol/L, 95% CI:-5.39 to 4.74; week 8: MD = 6.22 μmol/L, 95% CI:-24.04 to 36.48), decrease NCT(week 8: MD = 3.93, 95% CI:-0.72 to 8.58), improve MHE(week 4: OR = 0.93, 95% CI: 0.45 to 1.91; week 12: OR = 0.73, 95% CI: 0.35 to 1.51) and prevent the development of overt HE(week 4: OR = 0.96, 95% CI: 0.17 to 5.44; week 12:OR = 2.7, 95% CI: 0.50 to 14.64) in patients with liver cirrhosis. However, lactulose appears to be more effective in reducing NCT values as compared to probiotics(week 4: MD = 6.7, 95% CI: 0.58 to 12.82).Conclusion: Probiotics can decrease serum ammonia and endotoxin levels, improve MHE, and prevent overt HE development in patients with liver cirrhosis.     

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.     

Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis

Minimal hepatic encephalopathy (MHE) corresponds to the earliest stage of hepatic encephalopathy (HE). MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests. MHE may affect daily activities and reduce job performance and quality of life. MHE can increase the risk of accidents and may develop into overt encephalopathy, worsening the prognosis of patients with liver cirrhosis. Despite a lack of consensus on the therapeutic indication, interest in finding novel strategies for prevention or reversion has led to numerous clinical trials; their results are the main objective of this review. Many studies address the treatment of MHE, which is mainly based on the strategies and previous management of overt HE. Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia, and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose, antibiotics such as rifaximin, and administration of different probiotics. This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.     

轻微型肝性脑病诊断研究进展

轻微型肝性脑病常并发于肝硬化及各种门体分流术患者。由于缺乏典型的临床表现及生化异常,只能通过心理智能测试及神经电生理等检查发现,其发病率已升至30%～84%。轻微型肝性脑病可对患者的日常生活造成影响,无干预的轻微型肝性脑病易发展为显性肝性脑病。该病尚无公认的诊断“金标准”。本文介绍了国内外对轻微型肝性脑病的诊断方法。     

Quality of life in patients with minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) represents the mildest type of hepatic encephalopathy (HE). This condition alters the performance of psychometric tests by impairing attention, working memory, psychomotor speed, and visuospatial ability, as well as electrophysiological and other functional brain measures. MHE is a frequent complication of liver disease, affecting up to 80% of tested patients, depending of the diagnostic tools used for the diagnosis. MHE is related to falls, to an impairment in fitness to drive and the development of overt HE, MHE severely affects the lives of patients and caregivers by altering their quality of life (QoL) and their socioeconomic status. MHE is detected in clinically asymptomatic patients through appropriate psychometric tests and neurophysiological methods which highlight neuropsychological alterations such as video-spatial orientation deficits, attention disorders, memory, reaction times, electroencephalogram slowing, prolongation of latency evoked cognitive potentials and reduction in the critical flicker frequency. Several treatments have been proposed for MHE treatment such as non-absorbable disaccharides, poorly absorbable antibiotics such rifaximin, probiotics and branched chain amino acids. However, because of the multiple diagnosis methods, the various endpoints of treatment trials and the variety of agents used in trials, to date the treatment of MHE is not routinely recommended apart from on a case-by-case basis. Aim of this review is analyze the burden of MHE on QoL of patients and provide a brief summary of therapeutic approaches.     

Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China

AIM:To construct normal values for the tests of the psychometric hepatic encephalopathy score(PHES)and to evaluate its usefulness in the diagnosis of minimal hepatic encephalopathy(MHE)among Chinese individuals with cirrhosis.METHODS:The five tests of PHES,number connection test-A(NCT-A),number connection test-B,serial dotting test,line tracing test and digit symbol test(DST),were administered to all enrolled subjects in a quiet room with sufficient light.Cirrhotic subjects with overt HE were excluded by the West-Haven criteria and a detailed neurological examination.Based on the nomograms of healthy volunteers,the patients were classified as having MHE when their PHES was less than-4.RESULTS:In total,146 healthy volunteers completed all the PHES tests.Age and education years were confirmed to be predictors of all five tests.In total,53patients with liver cirrhosis completed the PHES.Of the patients with liver cirrhosis,24(45.3%),22(41.5%)and 7(13.2%)had Child-Pugh grades A,B and C,respectively.MHE was diagnosed in 26 patients(49.1%).Compared with compensated cirrhotic patients(Child A),decompensated cirrhotic patients(Child B and C)had a higher proportion of MHE(65.5%vs 29.2%).No differences in age and education years were found between the MHE and non-MHE groups.NCT-A and DST were able to diagnose MHE with a sensitivity of 76.9%and a specificity of 96.3%(AUC=0.866,K=0.735).CONCLUSION:The proportion of MHE is associated with liver function.NCT-A and DST are simple tools that can be used for the diagnosis of MHE in China.     

Minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is the mildest form of spectrum of hepatic encephalopathy (HE). Patients with MHE have no recognizable clinical symptoms of HE but have mild cognitive and psychomotor deficits. The prevalence of MHE is high in patients with cirrhosis of liver and varies between 30% and 84%; it is higher in patients with poor liver function. The diagnostic criteria for MHE have not been standardized but rest on careful patient history and physical examination, normal mental status examination, demonstration of abnormalities in cognition and/or neurophysiological function, and exclusion of concomitant neurological disorders. MHE is associated with impaired health-related quality of life, predicts the development of overt HE and is associated with poor survival. Hence, screening all patients with cirrhosis for MHE using psychometric tests, and treatment of those patients diagnosed to have MHE has been recommended. Ammonia plays a key role in the pathogenesis of MHE, which is thought to be similar to that of overt HE. Thus, ammonia-lowering agents such as lactulose and probiotics have been tried. These agents have been shown to improve cognitive and psychometric deficits, and have good safety profile. Future studies will better define the role of other drugs, such as rifaximin, acetyl L-carnitine and L-ornithine L-aspartate.