乳果糖治疗亚临床肝性脑病的临床研究

目的 前瞻性对比乳果糖长、短程治疗对亚临床肝性脑病(SHE)的效果及其对SHE病程的影响。方法 经智力测验(数字连接试验和数字符号试验之一异常)诊断的SHE 64例随机分入对照组(21例)、短程组(21例)和长程组(22例),后2组分别服乳果糖达8周和24周。治疗前以及治疗后每间隔8周行血氨、智力测验和体感诱发电位(SEP)等检查,共随访24周。结果 每组各有20例完成追踪。与对照组和治疗前相比,长程组血氨和智力测验显著改善(P＜0．05—0．01)且SEP的N50波潜伏期稳定不变,短程组治疗到第8周也有改善(P＜0．05),但停药后又逐渐恶化。对照组的血氨、智力测验和N50波潜伏期逐渐恶化,在16周时后2项与治疗前差异有显著性(P＜0．05—0．01);而长程组血氨持续降低,其肝性脑病(HE)患病率(5％)显著低于短程组(30％)和对照组(40％)(P＜0．05)。结论 乳果糖维持治疗能够降低血氨、改善智力测验结果并可能防止SEP的恶化,最终降低HE的患病率。     

Prevalence of subclinical hepatic encephalopathy in patients with cirrhosis determined by psychometric tests

OBJECTIVE: To investigate the prevalence of subclinical hepatic encephalopathy (SHE) in patients with stable hepatic cirrhosis. METHODS: One hundred and seventy‐five consecutive cirrhotic patients (mean age 53 years, range 27?72 years) without overt clinical encephalopathy were screened for SHE using the number connection test (NCT) part A and symbol digit test (SDT). Subclinical hepatic encephalopathy was defined as the presence of at least one abnormal psychometric test. The age‐corrected normal value was defined as the mean ± 2SD obtained from 356 subjects without liver disease and in normal mental condition. Illiterate patients and patients with concurrent use of alcohol or psychotropic drugs, and those with previous portosystemic shunt and were excluded. RESULTS: In different age subgroups, the NCT scores and SDT quotients for cirrhotic patients were significantly different compared with those for controls (P < 0.05?0.001). Fifty patients (28.6%) were found to be abnormal in both the NCT and SDT, 16 (9.1%) patients were abnormal only in the SDT and 34 patients (19.4%) only in the NCT. Taken together, SHE was diagnosed in 100 patients (57.1%) by using the two tests. The prevalence of SHE increased from 46.8% and 53.0% in Child?Pugh grades A and B, to 76.6% in Child?Pugh grade C (P < 0.05). No significant correlation was found between the development of SHE and the etiology of cirrhosis, patient age and smoking habit. CONCLUSION: By using a combination of NCT and SDT, SHE was diagnosed in 57.1% of cirrhotic patients without overt clinical encephalopathy. The prevalence of SHE was significantly correlated with the severity of liver cirrhosis.     

Predictors of nonresponse to lactulose for minimal hepatic encephalopathy in patients with cirrhosis

Background/Aims: Minimal hepatic encephalopathy (MHE) impairs health‐related quality of life and predicts overt hepatic encephalopathy (HE) in cirrhotic patients. Lactulose is effective in the treatment of MHE. However, not all patients respond to lactulose. We evaluated predictors of nonresponse to lactulose. Patients and methods: Consecutive 110 cirrhotic patients without HE were evaluated for MHE by psychometry, P300 auditory event‐related potential (P300ERP), venous ammonia and critical flicker frequency (CFF). MHE was diagnosed by abnormal psychometry and P300ERP (>2 SD). MHE patients were treated with lactulose for 1 month. Response was defined by normalization of the abnormal test parameters (both psychometric tests and P300ERP). Results: Sixty patients (54.5%) were diagnosed as having MHE: 17/39 (44%) in Child's A, 21/42 (50%) Child's B and 22/29 (76%) in Child's C. There was a significant difference between Child's C's vs Child's A's and B's (P<0.05). Abnormal psychometric tests and abnormal P300ERP were seen in 74 (67%) and 74 (67%) patients respectively. Of 60 patients with MHE, after treatment, psychometry remained abnormal in 22 (36.6%) and P300ERP in 21 (35%) patients. CFF was<38 Hz in 34 (57%) and 11 (18%) patients, respectively, before and after treatment in MHE patients. There was a significant difference between the baseline serum sodium level (134.7±2.6 vs 131.1±2.2 mmol/L, P=0.001) and the venous ammonia level (76.6±20.7 vs 113.4±22.8 μmol/L, P=0.001) between responders vs nonresponders. Receiver operating characteristic analysis was performed to identify the cutoff for venous ammonia [cutoff 93.5 mmol/L, area under the curve (AUC) 0.892 (0.814–0.970)] and for the serum sodium level [cutoff 132.5 mmol/L, AUC 0.874 (0.779–0.998)]. Taking a cutoff of 93.5 mmol/L for ammonia patient had a sensitivity of 88.5% and a specificity of 79.4%, respectively, and a cutoff of 132.5 mmol/L for serum sodium patient had a sensitivity of 76.5% and a specificity of 88.5% for nonresponse to lactulose. On univariate analysis and multivariate analysis, serum sodium and venous ammonia were the only two parameters associated with nonresponse to lactulose. Conclusion: The prevalence of MHE was 55% and MHE improved in 57% patients with lactulose. Baseline low serum sodium and high venous ammonia were highly predictive of nonresponse to lactulose therapy.     

Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis

BACKGROUND AND AIMS: The natural history of subclinical hepatic encephalopathy (SHE) is unknown. The present study was conducted to study the prevalence and the natural history of SHE in patients with cirrhosis of the liver. METHODS: One hundred and sixty-five patients with cirrhosis of the liver were studied. A total of nine psychometric tests (trail making and Wechsler adult intelligence scale-performance (WAIS-P) tests) were administered. Subclinical hepatic encephalopathy was present if two or more psychometric tests were abnormal. Seventy-two patients (SHE 40, without SHE 32) also underwent serial psychometric testing on follow-up visits at 6-8 week intervals. RESULTS: Subclinical hepatic encephalopathy was present in 103 (62.4%) patients. The number and figure connection, block design and picture completion tests were the most useful in the detection of SHE. Severity of SHE, as assessed by the number of abnormal tests, was greater in patients with more severe liver disease. During follow up, SHE tended to persist or worsen in patients with poorer liver function. Although other clinical complications were similar in different groups, overt hepatic encephalopathy developed more commonly in those patients who had SHE at entry compared to those who did not (22.6 vs 5.6%, P = 0.044). Among the patients with SHE, the development of overt hepatic encephalopathy was more common in patients with Child's score of > 6 than with Child's score of 相似文献   

Can Lactobacillus acidophilus improve minimal hepatic encephalopathy? A neurometabolite study using magnetic resonance spectroscopy

Background and study aimsMinimal hepatic encephalopathy (MHE) is diagnosed when hepatic patients perform worse on psychometric tests compared to healthy controls. This study aimed to evaluate probiotics as alternative therapy in MHE.Patients and methodsThis is an open-label randomised controlled trial, performed in the Department of Tropical Medicine and Infectious Diseases, Tanta University Hospitals, from March 2010 to January 2012. A total of 90 patients with MHE were allocated by simple randomisation to three parallel equal groups. Group A received lactulose, group B a probiotic (Lactobacillus acidophilus) and group C served as the control. After informed consent, patients were tested for gut micrecology, fasting blood ammonia, liver functions and magnetic resonance spectroscopy (MRS) examination to study brain metabolites, mainly choline (Cho), myo-inositol (mI), glutamine + glutamate (Glx) and creatinin (Cre). Patients who developed overt encephalopathy were excluded from analysis. The whole battery of investigations was repeated in the same order after 4 weeks.ResultsThe probiotic was better tolerated than lactulose. The relative risk reduction (RRR) of developing overt encephalopathy was 60% in the case of lactulose and 80% in the case of probiotic, with a number needed to treat (NNT) of 2.4 and 2.3, respectively. The differential but not total microecology count was significantly shifted towards saccharolytic rather than proteolytic bacteria. The mI/Cre and (Cho + mI)/Glx ratios were significantly increased and the Glx/Cre ratio was significantly reduced after 1 month-follow-up in the probiotic group compared to the lactulose group and in both treatment groups compared to the control group.ConclusionBoth probiotic and lactulose therapy can improve blood ammonia and psychometric tests in MHE and reduce the risk of developing overt encephalopathy. MRS showed more improvement in the levels of brain neurometabolites in the probiotic group.     

Primary prophylaxis of overt hepatic encephalopathy in patients with cirrhosis: an open labeled randomized controlled trial of lactulose versus no lactulose

Background and Aim: Development of overt hepatic encephalopathy (HE) is associated with poor prognosis in patients with cirrhosis. Lactulose is used for the treatment of HE. There is no study on the prevention of overt HE using lactulose in patients who never had HE earlier. Methods: Consecutive cirrhotic patients who never had an episode of overt HE were randomized to receive lactulose (Gp‐L) or no lactulose (Gp‐NL). All patients were assessed by psychometry (number connection test [NCT‐A and B], figure connection test if illiterate [FCT‐A and B], digit symbol test [DST], serial dot test [SDT], line tracing test [LTT]) and critical flicker frequency test (CFF) at inclusion and after 3 months. These patients were followed every month for 12 months for development of overt HE. Results: Of 250 patients screened, 120 (48%) meeting the inclusion criteria were randomized to Gp‐L (n = 60) and Gp‐NL (n = 60). Twenty (19%) of 105 patients followed for 12 months developed an episode of overt HE. Six (11%) of 55 in the lactulose (Gp‐L) group and 14 (28%) of 50 in the Gp‐NL (P = 0.02) developed overt HE. Ten (20%) of 50 patients in Gp‐NL and five (9%) of 55 patients in the Gp‐L group died, P = 0.16. Number of patients with minimal hepatic encephalopathy (MHE) were comparable in two groups at baseline (Gp‐L vs Gp‐NL, 32:36, P = 0.29). Lactulose improved MHE in 66% of patients in Gp‐L. Taking a cutoff < 38 Hz sensitivity and specificity of CFF in predicting HE were 52% and 77% at baseline and 52% and 82% at 3 months of treatment. On multivariate analysis, Child's score and presence of MHE at baseline were significantly associated with development of overt HE. Conclusions: Lactulose is effective for primary prevention of overt hepatic encephalopathy in patients with cirrhosis.     

Prevalence of subclinical hepatic encephalopathy in cirrhotic patients in China

AIM: Subclinical hepatic encephalopathy (SHE) is a common complication of liver diseases. The aim of this study was to find out the normal value of psychometric test and to investigate the prevalence of SHE in Chinese patients with stabilized hepatic cirrhosis.METHODS: Four hundred and nine consecutive cirrhotic patients without overt clinical encephalopathy were screened for SHE by using number connection test part A (NCT-A) and symbol digit test (SDT). SHE was defined as presence of at least one abnormal psychometric test. The age-corrected normal values were defined as the mean&#177;2times standard deviation (2SD), and developed in 356 healthypersons as normal controls. Four hundred and sixteen patients with chronic viral hepatitis were tested as negative controls to assess the diagnostic validity of this test battery.RESULTS: There was no significant difference in NCT scores and SDT quotients between healthy controls and chronic hepatitis group (P&gt;0.05). In all age subgroups,the NCT and SDT measurements of cirrhotic patients differed significantly from those of the controls (P&lt;0.05).When mean&#177;2SD of SDT and NCT measurements from healthy control group was set as the normal range, 119 cirrhotic patients (29.1%) were found to have abnormal NCT-A and SDT tests, 53 (13.0%) were abnormal only in SDT and 36 (8.8%) only in NCT-A. Taken together, SHE was diagnosed in 208 (50.9%) cirrhotic patients by this test battery. The prevalence of SHE increased from 39.9% and 55.2% in Child-Pugh‘s grade A and B groups to 71.8% in Child-Pugh‘s grade C group (P&lt;0.05). After the adjustment of age and residential areas required from the tests, no correlation was found in the rate of SHE and causes of cirrhosis, education level and smoking habit.CONCLUSION: Psychometric tests are simple and reliable indicators for screening SHE among Chinese cirrhotic patients. By using a NCT and SDT battery, SHE could be found in 50.9% of cirrhotic patients without overt clinical encephalopathy. The prevalence of SHE is significantly correlated with the severity of liver functions.     

Critical flicker frequency for quantification of low-grade hepatic encephalopathy

Subclinical hepatic encephalopathy (SHE) is currently diagnosed by psychometric tests or neurophysiologic techniques. In view of its sociomedical relevance, simple and reproducible tests for routine diagnosis are required. This study evaluates critical flicker-frequency thresholds for quantification of low-grade hepatic encephalopathy. A total of 115 patients (92 with cirrhosis, 23 controls) were analyzed for HE severity (mental state, computerized psychometric tests), and the threshold frequencies at which light pulses are perceived as fused (fusion frequency) or flickering light (critical flicker frequency [CFF]). CFF was a highly reproducible parameter with little age, day-time, and training dependency. CFFs in cirrhotic patients without HE (HE 0) were not different from those found in noncirrhotic controls. Significantly lower CFFs were found in cirrhotic patients with subclinical or manifest HE, and the various HE groups separated from each other at a high level of significance (P <.01). By using a CFF cut-off value of 39 Hz, a 100% separation of patients with manifest HE from noncirrhotic controls and HE 0 cirrhotic patients was obtained. SHE patients separated from HE 0 cirrhotic patients with high sensitivity (55%) and specificity (100%). The HE severity-dependent differences were found in both, alcoholic and posthepatitic cirrhosis. Statistically significant correlations (P <.01) were found between CFFs and individual psychometric tests. Aggravation of preexisting HE after transjugular intrahepatic portosystemic stent shunt (TIPS) implantation was accompanied by a corresponding decrease of CFF, whereas improvement of HE increased CFF. In conclusion, CFF is a sensitive, simple, and reliable parameter for quantification of low-grade HE severity in cirrhotic patients and may be useful for the detection and monitoring of SHE.     

Hospitalizations During the Use of Rifaximin Versus Lactulose for the Treatment of Hepatic Encephalopathy

We sought to compare frequency and duration of hepatic encephalopathy-related hospitalizations during rifaximin versus lactulose treatment. Hospitalizations, clinical efficacy data, and adverse events obtained from charts of 145 patients with hepatic encephalopathy who received lactulose (30 cc twice daily) for ≥6 months and then rifaximin (400 mg 3 times a day) for ≥6 months compared last 6 months on lactulose (lactulose period) to first 6 months on rifaximin (rifaximin period). Fewer hospitalizations (0.5 versus 1.6; P < .001), fewer days hospitalized (2.5 versus 7.3; P < .001), fewer total weeks hospitalized (0.4 versus 1.8; P < .001), and lower hospitalization charges per patient ($14,222 versus $56,635) were reported during the rifaximin period. More patients had asterixis, diarrhea, flatulence, and abdominal pain during the lactulose period (P < .001). Treatment of hepatic encephalopathy with rifaximin was associated with lower hospitalization frequency and duration, lower hospital charges, better clinical status, and fewer adverse events.     

Diagnostic tools for the detection of subclinical hepatic encephalopathy: comparison of standard and computerized psychometric tests with spectral-EEG

The prevalence of subclinical hepatic encephalopathy (SHE) varies according to the diagnostic tool used in its detection. Since a standardised approach to the diagnosis of SHE is not yet available, we compared psychometric tests and EEG spectral analysis. On the same day 32 cirrhotic patients without overt hepatic encephalopathy and 18 controls were assessed by psychometric tests, both standard and computerized (CPT), and by EEG spectral analysis (EEG-SA). The CPT, measuring reaction time (Rt) and errors (er), were Font, Choice1, Choice2 and Scan test. The standard psychometric tests were the number connection test (NCT), the Reitan-B test, the Line Tracing Test [for time: LTT(t) and for errors: LTT(er)], and the Symbol Digit test (SD). Both psychometric tests [Reitan-B test, LTT(er) and CPT but Font (Rt) and Choice2 (er)] and EEG-SA parameters [mean dominant frequency (MDF) and theta power (%)] significantly correlated (p<0.05) with albumin plasma levels. LTT(er), Scan, Font, Choice1 and Choice2 were significantly related to % and MDF. There was no control with positive EEG-SA, though one control was positive with LTT(t) and with the number of errors made during Font and Scan tests. The percentage of cirrhotics with positive EEG-SA was 34% (CI_95%=19–53), while 9–66% were positive with psychometric tests, depending on the test considered. In spite of the correlation between neuropsychological and neurophysiological parameters, the diagnostic agreement between EEG-SA and each psychometric test was not high. In conclusion: 1) neurophysiological and neuropsychological impairment in cirrhotics without overt hepatic encephalopathy were found linked to each other and to hepatic dysfunction; 2) psychometric tests were not sufficiently good predictors of EEG alterations; therefore, neuropsychological tools can not substitute neurophysiological ones to detect CNS dysfunction in liver disease.     

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.     

Role of Helicobacter pylori infection and its eradication in patients with subclinical hepatic encephalopathy

AIMS: Helicobacter pylori infection in cirrhotic patients has been associated with episodes of hepatic encephalopathy (HE), although conclusive data are still lacking. This prospective study has evaluated the prevalence of H. pylori infection in 37 patients with advanced cirrhosis of the liver and subclinical hepatic encephalopathy (SHE), diagnosed by changes in psychometric tests and/or electrophysiological tests, as well as the repercussion of H. pylori eradication on ammonaemia and the evolution of this disorder. RESULTS: A positive result for H. pylori infection was obtained in 22/37 (59%) patients. Initial fasting blood levels of ammonia were high in both groups. Infected and non-infected patients showed similar levels (62.05 mmol/l v. 62.5 mmol/l), which were lowered by the standard diet, although statistical significance was only reached in the infected patient group (53.05 +/- 26 mmol/l; P < 0.05). Infection was eradicated in 19 patients, but no reduction of blood levels of ammonia was observed after H. pylori eradication among infected patients (52.37 +/- 29 mmol/l). No change has been found in either group after the administration of diet or antimicrobials with regard to psychometric and/or electrophysiological tests. CONCLUSIONS: H. pylori infection does not contribute significantly to high blood levels of ammonia in patients with advanced cirrhosis and SHE. Likewise, H. pylori eradication does not induce any improvement in the psychometric and/or electrophysiological tests used to define SHE.     

Oral Tryptophan Challenge Studies in Cirrhotic Patients: No Evidence of Neuropsychiatric Changes

Hepatic encephalopathy is a frequent complication of cirrhosis. Abnormalities of5-hydroxytryptamine (5-HT) and its metabolites are recognized and may contribute to its pathogenesis. We therefore studied the effect of an oral tryptophan load (6–18 g) upon psychometric test scores and analyzed EEG's in alcoholic cirrhotic patients. Eight patients had had previous encephalopathic episodes related to variceal bleeds and one patient was awaiting a liver transplant. Five out of the 10 patients had at least one abnormal baseline psychometric test. Following tryptophan challenge there were no changes in blood ammonia but plasma tryptophan levels were elevated approximately 10-fold (p <0.01× 10^–7). Nevertheless, there were no statistically significant changes in psychometric testing or analyzed EEG frequency distribution. All patients reported nausea or vomiting while one patient developed a short-lived serotonin like syndrome. We conclude that in this group of patients, an oral tryptophan load does not induce or worsen subclinical hepatic encephalopathy. If the high blood levels of tryptophan seen in these studies are able to influence cerebral neurotransmitter synthesis, the results do not support a primary role for abnormalities of 5-HT neurotransmission in hepatic encephalopathy.     

Helicobacter pylori Infection Is Not Associated with Subclinical Hepatic Encephalopathy in Stable Cirrhotic Patients

The importance of ammonia-producing Helicobacter pylori infection as a cause of subclinical encephalopathy in cirrhosis was investigated. In addition, a single psychometric test that can reliably detect subclinical hepatic encephalopathy was sought. Out-patients with cirrhosis and no overt encephalopathy underwent [¹⁴C]urea breath testing once and psychometric testing on two separate occasions, with an intervening course of clarithromycin/omeprazole if they had subclinical encephalopathy (two of four psychometric tests abnormal). Subclinical encephalopathy was present in 27 of 69 patients (39%), and Helicobacter pylori infection in 14 of 69 (20%). There was no association between the two conditions (P = 0.769). Subclinical encephalopathy resolved in 75% of treated Helicobacter pylori-positive patients and 37.5% of treated Helicobacter pylori-negative patients (P = 0.285). Number connection test-B had high reproducibility among untreated patients (R = 0.655) and high correlation (P 0.01) with three surrogate gold standards. In stable cirrhotic patients, subclinical hepatic encephalopathy was found to: (1) have a high prevalence, (2) not be associated with Helicobacter pylori infection, and (3) be readily detected with the number connection test-B alone.     

幽门螺杆菌感染对高氨血症和肝性脑病发病的影响

目的了解幽门螺杆菌(Hp)感染和血氨水平、肝性脑病(HE)发病的关系,并探讨根除Hp对血氨水平和HE发生的影响。方法2003年7月-2005年1月在浙江省5个地区收集肝硬化住院患者,记录患者的一般资料、数字连接试验结果、Hp感染情况、肝功能Child-Pugh分级、血氨水平和HE情况。Hp(+)患者予“奥美拉唑+克拉霉素+替硝唑”1周根除治疗,1个月后查~(14)C尿素呼气试验,并记录患者的神经精神症状和血氨水平。结果(1)共收集肝硬化住院患者457例,Hp感染率60．6%,HE发生率47．5%。检出亚临床肝性脑病(SHE)患者55例,SHE占未发生HE肝硬化患者的47．0%(55/117)。(2)Hp(+)和Hp(-)肝硬化患者血氨浓度分别为(78．4±63．6)μmoL/L和(53．8±51．4)μmol/L(P＜0．01);根除Hp后血氨显著下降至(53．5±37．7)μmol/L(P＜0．01)。Hp(+)和Hp(-)肝硬化患者HE发生率差异有统计学意义(58．5%比30．6%,P＜0．01);根除Hp后HE发生率下降至34．1%(P＜0．01)。(3)HE、SHE和肝硬化患者的Hp感染率分别为74．4%、69．1%和53．2%(P＜0．05)。三组患者的血氨水平分别为(94．5±75．6)μmol/L、(59．9±49．2)μmol/L和(47．3±33．5)μmol/L(P＜0．05)。结论Hp感染是引起肝硬化高氨血症和并发HE的重要因素,根除Hp有利于治疗和预防HE的发生。     

晚期血吸虫病并发亚临床肝性脑病的初步研究

目的 了解晚期血吸虫病（晚血）患者亚临床肝性脑病（ＳＨＥ）发生率。方法 对３２例无临床肝性脑病并发症的晚血患者进行智力测验及诱发电位检测,并与正常人群比较,智力测验和（或）诱发电位异常者诊为ＳＨＥ。结果 ＳＨＥ发生率为２８．１％。结论 晚血并发ＳＨＥ较为普遍,加强诊治具有重要意义。     

Helicobacter pylori infection, plasma ammonia levels, and psychometric testing in cirrhotic patients

OBJECTIVE: The role of Helicobacter pylori (H. pylori) infection as a cause of hepatic encephalopathy is still debated. This study focused on the relationship between H. pylori, plasma ammonia levels, and intellectual function in cirrhotic patients. METHODS: Forty-seven cirrhotics with latent or mild hepatic encephalopathy were enrolled in the study, upon H. pylori assessment at endoscopy. Plasma ammonia level determinations and psychometric testing were performed at entry in all patients. Patients with H. pylori infection received a 2-wk standard dual therapy and bacterial eradication was assessed at endoscopy 6-8 wk later. On this occasion, plasma ammonia levels and psychometric assessments were repeated. Patients without H. pylori infection at entry were also studied after 6-8 wk for ammonia level assessment and psychometric testing, as a control group. Patients receiving lactulose therapy and those without therapy were grouped separately for statistical analysis. RESULTS: Among 21 patients without lactulose therapy (group A), basal plasma ammonia levels and psychometric testing scores did not significantly differ between 13 infected and eight uninfected patients. Similarly, among 26 patients undergoing lactulose therapy (group B), basal plasma ammonia concentration and psychometric testing scores did not significantly differ between 13 infected and 13 uninfected patients. Moreover, in group B, both the prevalence of previous overt hepatic encephalopathy episodes and the mean daily dose of lactulose therapy were similar between infected and uninfected patients. In addition, no significant reduction in the plasma ammonia concentrations and in psychometric testing scores emerged in both groups A and B after bacterial eradication. CONCLUSIONS: This study failed to find a relationship between H. pylori, plasma ammonia levels, and psychometric testing scores in cirrhotic patients with latent or mild hepatic encephalopathy.     

Bifidobacterium longum with Fructo-Oligosaccharide (FOS) Treatment in Minimal Hepatic Encephalopathy: A Randomized, Double-Blind, Placebo-Controlled Study

Minimal hepatic encephalopathy (MHE) describes patients with chronic liver disease or cirrhosis who have no clinical symptoms of brain dysfunction but perform worse on psychometric tests compared with healthy subjects. The pathogenesis of hepatic encephalopathy is controversial although ammonia has been found to induce cerebral dysfunction. Increased intestinal ammonia production is due to bacterial urease activity and the production of other toxin methabolities, such as mercaptans, thioles. This study assesses the clinical efficacy of Bifidobacterium longum plus fructo-oligosaccharides (FOS) in the treatment of MHE. A total of 60 cirrhotic patients were randomly and equally divided into two groups receiving Bifidobacterium+FOS (17 males, 13 females; mean age, 46±11 years) or placebo (16 males, 14 females; mean age, 45±12 years), respectively. All patients underwent clinical and laboratory assessment psychometric tests and automated EEG analysis: neurophysiological assessment, liver function assessment, amd neuropsychological assessment. After 90 days of treatment, fasting NH₄ serum levels were significantly decreased (P=0.003), performance on Trail Making Test-A was significantly decreased (P=0.000), performance on Trail Making Test-B was significantly decreased (P=0.000), performance on the symbol digit modalities test was significantly improved (P<0.05), performance on block design was significantly improved (P=0.000), and performance on the MMSE test was significantly improved (P=0.000). We conclude that the improvement in biochemical and neuropsychological tests of the group treated with Bifidobacterium longum+FOS are interesting and merit further, close examination.     

Vegetable versus animal protein diet in cirrhotic patients with chronic encephalopathy. A randomized cross-over comparison

Abstract. In a randomized cross-over comparison, the effects of a mainly vegetable protein diet were compared with an animal protein diet in eight patients with cirrhosis and chronic permanent encephalopathy, under optimum lactulose therapy. After a run-in period, patients were fed two equi-caloric, equi-nitrogenous diets for 7 days (71 g total proteins), containing either 50 g protein of animal origin or 50 g vegetable proteins. In the last 3 days of each period, nitrogen balance was significantly better during the vegetable protein diet (+ 0.2 (SD 1.4) g vs. — 1.7 (2.4): P < 0.01), the difference being entirely due to a reduced urinary nitrogen excretion. Average daytime integrated blood glucose was slightly higher during vegetable proteins, whereas insulin, plasma amino acids and ammonia were lower. The clinical grading of encephalopathy improved slightly on vegetable proteins, and psychometric tests improved significantly, but remained grossly abnormal. Compliance to dietary manipulation was good. The data prove that a mainly vegetable protein diet is worthwhile in cirrhotic patients with chronic encephalopathy under optimum lactulose therapy. Improved nitrogen balance may be related to more effective nitrogen use for protein synthesis, probably due to blunted hormonal response, and largely outweighs the effects on encephalopathy.     

Cerebral changes in hepatic encephalopathy

Hepatic encephalopathy (HE) accompanied by an impairment of consciousness from orientation disorder (grade II) to coma (grade IV) is considered to be overt HE and is treated as an emergency. However, subclinical hepatic encephalopathy (SHE) can be detected by sensitive and quantitative neuropsychological examinations in cirrhotic patients without overt HE. The introduction of the SHE concept is clinically important for preventing the deterioration of SHE (grades 0 and I) to overt HE (grade II and more severe), prolonging the compensated state of cirrhosis without its deterioration to hepatic failure, and the continuation of patient treatment at home. We developed a new diagnostic method for SHE using a quantitative neuropsychological test, with the computerization of all operations. Evaluations of cerebral function and morphology are useful for the determination of the patho-physiology of HE, and assist the diagnosis of SHE. The latencies of the P3 wave in the visually evoked potential and the P300 wave in the event-related potential are prolonged in cirrhotic patients with SHE and are well expressed in three-dimensional coloured topograms (brain mapping). Automated polysomnographic analysis is useful for continuous-monitoring electroencephalograms (EEG) and for the detection of the sleep disturbance observed in cirrhotic patients with SHE. Brain atrophy in computed tomography (CT), magnetic resonance imaging (MRI) and high signals in the basal ganglia in the MR-T1-weighted images have frequently been observed in patients with SHE. The reduction of regional cerebral blood flow (rCBF) by ^99mtechnetium-1, 1-ethylcysteinate dimer (^99mTc-ECD)-single photon emission computed tomography (SPECT) and the choline/N-acetylaspartic acid ratio by ¹proton-magnetic resonance spectroscopy (¹H-MRS) were observed in the hippocampus in patients with SHE. These approaches (cerebral function tests and imaging diagnoses of the brain) can also be used to evaluate the effectiveness of treatments for HE; for example, branched-chain amino acid (BCAA) was shown by automated continuous polysomnographic analysis to be a psychotropic drug which acts directly on the central nervous system and the clinical significance of choline administration to HE patients is now being evaluated by ¹H-MRS and neuropsychological tests.