肝性脑病发病机制新进展

肝性脑病是急性肝功能衰竭和肝硬化患者常见的并发症,表现为从轻微认知障碍到昏迷等一系列神经症状。根据临床表现可分为轻微肝性脑病、明显肝性脑病和昏迷;依据基础肝病的类型,HE分为A、B、C 3型。10%～50%接受门体静脉分流术的患者1年内可发生明显的B型肝性脑病。肝性脑病是影响预后的不利因素,1年内病死率为54%～85%。肝性脑病的发病机制尚未明确,本文通过对肝性脑病发病机制的阐述,以期对临床诊断及治疗提供帮助。     

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。     

肝性脑病的诊断方法及其研究进展

肝性脑病（hepatic encephalopathy,HE）是肝脏功能衰竭或门体分流引起的中枢神经系统神经精神综合征。对肝性脑病患者的早期诊断与识别非常关键,因为早期肝性脑病易于控制与逆转,发展至肝昏迷时治疗效果差。然而,肝性脑病（包括轻微型肝性脑病）尚无诊断的金标准。本文就近年来肝性脑病的主要诊断方法及其研究进展作一综述。     

轻微肝性脑病的诊断方法

轻微肝性脑病（MHE）过去被称为亚临床型肝性脑病（SHE）,是指临床上无明显肝性脑病相关症状和生化异常,但用精细的智力试验或神经电生理检查可见智力、神经、精神的异常而诊断的肝性脑病。患者虽形似正常,但操作能力和应急反应能力减低,在从事高空作业、机械或驾驶等工作时容易发生意外。但目前轻微肝性脑病的诊断尚无统一标准,本文综述了国内外MHE的相关诊断方法。     

轻微肝性脑病的MRI与^1H-MRS探讨

目的探讨轻微肝性脑病患者颅脑MRI及^1H-MRS的代谢变化。方法 22例经神经心理测试诊断为轻微肝性脑病患者和13例年龄、性别和受教育程度相匹配的健康志愿者,行MRI、^1H-MRS扫描,^1H-MRS兴趣区为双侧基底节。结果 22例患者中17例双侧基底节在T1WI上可见高信号,NAA/Cr值患者组与健康对照组之间差异无显著性（P〉0.05）,而mI/Cr和Cho/Cr值患者组与健康对照组比较显著降低（L：P〈0.01;R：P〈0.01）。结论 T1WI高信号是诊断轻微肝性脑病较为特征性征象,1HMRS能够无创性观察到轻微肝性脑病患者的脑代谢异常,有助于揭示肝性脑病的病理生理机制。     

小肠细菌过度生长相关性轻微肝性脑病患者的血氨变化

目的 观察肝硬化患者小肠细菌过度生长相关性轻微肝性脑病(MHE)患者的血氨水平.探讨血氨与轻微肝性脑病的关系.方法 对90例肝硬化患者及20例健康志愿者进行血氨、葡萄粮氢呼气试验、数宁连接试验和数字符号试验检测.观察小肠细菌过度生长相关性轻微肝性脑病患者的血氨水平差异.结果 肝硬化组小肠细菌过度生长(36.7%,33/90)明显高于健康对照组(5%,1/20).20名健康志愿者未检出 MHE;90例肝硬化患者轻微肝性脑病37例(41.1%),其中伴小肠细菌过度生长肝硬化患者轻微肝性脑病发生率高于不伴小肠细菌过度生长患者.血氨水平均正常,但肝硬化组血氨水平高于健康对照组;肝硬化小肠细菌过度生长组血氨水平(47.9 μmol/L±7.8 μmol/L)高于无小肠细菌过度生长组(34.2μmol/L±6.8 μoL/L,P<0.05);轻微肝性脑病组血氨水平(46.2μmol/L±5.9μmoL/L)高于无轻微肝性脑病组(33.9μmol/L±7.6μmol/L,P<0.05).应用抗生素抑制小肠细菌过度生长及乳果糖治疗1周后葡萄糖氧呼气试验(GHBT)、血氨水平、数字连接试验(NCT-A、NCT-BC)及数字符号试验(DST)检查结果改善.结论 血氨对伴小肠细菌过度生长的轻微肝性脑病的发生及进展可能有一定的关系.     

事件相关电位P300和简易智能精神状态检查在轻微型肝性脑病检测中的价值

目的:评价事件相关电位P_(300)和智能精神状态检查(MMSE)诊断轻微型肝性脑病(MHE)的价值.方法:30例肝炎后肝硬化患者进行事件相关电位P_(300)和脑诱发电位检查及MMSE检测,并观察1 a后临床肝性脑病(HE)的出现情况.结果:事件相关电位P_(300)异常21例(70.0%),体感诱发电位(SEP)异常11例(36.7%),MMSE得分<27(提示有认知功能障碍)13例(43.3%),事件相关电位P_(300)和/或MMSE异常22例(73.3%),两者均异常10例(33.3%),追踪观察1 a的23位患者中,17例事件相关电位P_(300)和/或MMSE异常患者出现临床肝性脑病12例,两者均无异常的6例患者中,出现临床肝性脑病1例,两者比较有显著性差异(70.6% vs 16.7%,P<0.05).结论:事件相关电位P_(300)和MMSE可作为判断肝硬化失代偿期是否发生轻微型肝性脑病的一种敏感又可靠的方法.     

肝硬化患者合并轻微肝性脑病的治疗时间

<正>【据《Ann Hepatol》2017年2月报道】题:肝硬化患者合并轻微肝性脑病的治疗时间(作者Goyal O等)众所周知,轻微肝性脑病在经过短期治疗后病情容易复发,目前还没有关于轻微肝性脑病停止治疗后的复发率的相关研究报道。来自印度达耶难陀医学院的Goyal等旨在评估短期(3个月)乳果糖或利福昔明治疗后轻微肝性脑病的长期(9个月)缓解率。共纳入患者527例,筛选出适合的研究对象351例,其中112例(31.9%)为轻微肝性脑病患者(平均年龄     

中国肝性脑病诊治共识意见(2013年,重庆)

一、肝性脑病的概念及其发展过程史 肝性脑病(hepatic encephalopathy)是一种由于急、慢性肝功能严重障碍或各种门静脉-体循环分流(以下简称门-体分流)异常所致的、以代谢紊乱为基础的、轻重程度不同的神经精神异常综合征.轻微型肝性脑病(minimal hepatic encephalopathy)常无明显临床症状,只有通过神经心理测试才能发现.绝大多数肝硬化患者在病程中的某些阶段会出现不同程度的轻微型肝性脑病和(或)肝性脑病,是严重肝病常见的并发症及死亡原因之一.过去所称的肝昏迷(hepatic coma),只是肝性脑病中程度严重的一级,并不能代表肝性脑病的全部.     

“ECHO临床病例征集项目”通知

<正>为提高对肝硬化导致的高血氨症及肝性脑病的临床诊疗水平,从而改善对肝硬化患者的管理,上海市感染性疾病科临床质量控制中心和《肝脏》杂志社与卫材(中国)药业有限公司合作设立"ECHO临床病例征集项目",病例征集范围为肝性脑病(轻微型肝性脑病/显性肝性脑病)或肝源性高血氨症患者,旨在进一步推进肝功能衰竭及肝硬化治疗的发展,为中青年医师提供学术交流的机会。     

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.     

Is it a medical error if we do not screen cirrhotic patients for minimal hepatic encephalopathy?

Minimal hepatic encephalopathy (MHE) refers to subtle neurocognitive and neurophysiological defects in patients with liver cirrhosis without clinical signs of hepatic encephalopathy. Using appropriate diagnostic methods the prevalence of MHE is approximately 25-30%. MHE has clinical significance as it results in a diminished daily functioning, precedes overt hepatic encephalopathy and is associated with a poor prognosis. Treatment with non-absorbable disaccharides can reverse the neurocognitive and neurophysiological defects found in MHE. The failure to diagnose MHE in apparently normal cirrhotic patients could, therefore, be considered a medical error. However, whether treatment also improves patients' quality of life and prognosis remains to be determined.     

Advances in the Evaluation and Management of Minimal Hepatic Encephalopathy

Minimal hepatic encephalopathy (MHE) is a neurocognitive disorder that affects up to 80% of cirrhotic patients. Similar to overt hepatic encephalopathy, ammonia and oxidative stress play key roles in the pathogenesis of MHE. However, MHE is characterized by subtle deficits and psychomotor abnormalities that can only be elicited by specialized psychometric tests. Although no gold standard exists for the diagnosis, MHE remains an important entity for clinicians to recognize because of its negative impact on a patient’s health-related quality of life and association with driving impairment and vehicle accidents. MHE has also been associated with an increased rate in the development of overt hepatic encephalopathy and increased mortality; therefore, identification and treatment should not be delayed. Treatment to date has been focused on reducing serum ammonia levels with agents such as lactulose, probiotics, and synbiotics. MHE is a real and growing problem that is epidemic in cirrhosis, and increasing awareness of this condition is necessary for adequate management of these patients.     

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.     

Assessment of minimal hepatic encephalopathy (with emphasis on computerized psychometric tests)

Minimal hepatic encephalopathy (MHE) is associated with a high risk of development of overt hepatic encephalopathy, impaired quality of life, and driving accidents. The detection of MHE requires specialized testing because it cannot, by definition, be diagnosed on standard clinical examination. Psychometric and neurophysiologic techniques are often used to test for MHE. Paper-pencil psychometric batteries and computerized tests have proved useful in diagnosing MHE and predicting its outcomes. Neurophysiologic tests also provide useful information. The diagnosis of MHE is an important issue for clinicians and patients alike. Testing strategies depend on the normative data available, patient comfort, and local expertise.     

Critical flicker frequency for diagnosis and assessment of recovery from minimal hepatic encephalopathy in patients with cirrhosis

BACKGROUND:Minimal hepatic encephalopathy (MHE) impairs quality of life and predicts overt hepatic encephalopathy (HE) in cirrhotic patients.Diagnosis of MHE requires cumbersome tests.Lactulose is effective in the treatment of MHE.This study aimed to evaluate the use of critical flicker frequency (CFF) for the diagnosis of MHE in cirrhotic patients after treatment.METHODS:One hundred and ten patients were evaluated by psychometry (number connection tests A,B or figure connection tests A,B),P300 auditory eve...     

Minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE), formerly known as subclinical hepatic encephalopathy, is the mild cognitive impairment commonly seen in patients who have cirrhosis. Current understanding suggests that MHE forms part of the spectrum of hepatic encephalopathy, although this remains to be proven. Although traditionally viewed as having negligible clinical significance, MHE has a significant impact on quality of life. MHE often goes undiagnosed because in many patients there is no evidence of clinically overt signs of impaired cognition. In addition, the diagnostic criteria for MHE have not been standardized, which means that the exact characteristics of MHE remain in question. This Review focuses on the pathogenesis and neuropsychological findings (incorporating neuroimaging) of MHE, as well as the effect of MHE on quality of life and survival, and developments in treatment.     

Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy

BACKGROUND/AIMS: We assessed the usefulness of oral glutamine challenge (OGC) and minimal hepatic encephalopathy in evaluating risk of overt hepatic encephalopathy in cirrhotic patients.METHODS: Minimal hepatic encephalopathy (MHE) was inferred using neuro-psychological tests. Venous ammonia concentrations were measured pre- and post-60 min (NH(3)-60m) of a 10 g oral glutamine load. Receiver-operating-characteristic curve analysis indicated a pathological glutamine tolerance cut-off value of NH(3)-60m >128 microg/dl. RESULTS: In healthy control subjects (n=10) ammonia concentrations remained unchanged but increased significantly in cirrhotic patients (from 70.41+/-45.2 to 127.43+/-78.6; P<0.001). In multiple logistic regression analysis, altered OGC was related to Child-Pugh (odds ratio, OR=7.69; 95% confidence interval, CI=1.72-33.3; P<0.01) and MHE (OR=5.45; 95% CI=1.17-25.4; P<0.05). In the follow-up 11 patients (15%) developed overt hepatic encephalopathy (HE). In multivariate analysis OGC (OR=14.5; 95% CI=1.26-126.3) and MHE (OR=1.56; 95% CI=1.02-21.9) were independently related with HE in the follow-up. Patients with MHE and altered OGC showed significantly higher risk of overt HE in the follow-up (60%) than patients without MHE and normal OGC (2.8%) (Log rank test=21.60; P<0.0001). CONCLUSIONS: A pathological OGC in patients with MHE appears to be a prognostic factor for the development of overt hepatic encephalopathy, whereas a normal OGC in patients without MHE could exclude risk of overt HE.     

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.     

Minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy and can affect up to 80% of cirrhotic patients. By definition, it has no obvious clinical manifestation and is characterized by neurocognitive impairment in attention, vigilance and integrative function. Although often not considered to be clinically relevant and, therefore, not diagnosed or treated, MHE has been shown to affect daily functioning, quality of life, driving and overall mortality. The diagnosis of MHE has traditionally been achieved through neuropsychological examination, psychometric tests or the newer critical flicker frequency test. A new smartphone application (EncephalApp Stroop Test) may serve to function as a screening tool for patients requiring further testing. In addition to physician reporting and driving restrictions, medical treatment for MHE includes non-absorbable disaccharides (eg, lactulose), probiotics or rifaximin. Liver transplantation may not result in reversal of the cognitive deficits associated with MHE.