Management Of Minimal Hepatic Encephalopathy Research Articles

Lactulose Management of Minimal Hepatic Encephalopathy

Minimal hepatic encephalopathy has been shown to increase risk of involvement in road traffic accidents and alter quality of life. This systematic review focused on the role of nonabsorbable disaccharides for the management of minimal hepatic encephalopathy. Randomized clinical trials that evaluated medical management of minimal hepatic encephalopathy were considered for inclusion. Individual studies compared lactulose with usual care and lactulose with probiotics and L-ornithine-L-aspartate. The outcome for examination was the neuropsychiatric test for cognitive function. Search strategies outlined by the Johanna Briggs Institute were used, and articles and references of selected articles were reviewed according to that methodology. Meta-analyses and narrative synthesis of the included studies were undertaken. Treatment of minimal hepatic encephalopathy with lactulose, probiotics, or L-ornithine-L-aspartate was seen to be equally effective in reducing abnormal tests at 1, 3, and 12 months post-treatment. All patients with minimal hepatic encephalopathy should be screened using a neuropsychiatric test and receive treatment as needed. Treatment can delay or eliminate risky automobile accidents and harm to self. Lactulose, probiotics, and L-ornithine-L-aspartate are a low-cost alternative compared with antibiotic treatment.

The Role of L-ornithine-L-aspartate in the Management of Minimal Hepatic Encephalopathy among Patients with Liver cirrhosis: a Systemic review and Meta-analysis

Objective. To evaluate the efficacy of L-ornithine-L-aspartate (LOLA) in improving minimal hepatic encephalopathy in adult patients with liver cirrhosis.
 Methods. A search in PubMed, Cochrane Library, Google Scholar, and Medline was made obtaining four qualified randomized controlled trials. Studies included adult cirrhotic patients with minimal hepatic encephalopathy measured by the number connection test (NCT-A, B), figure connection test (FCT-A, B), picture completion, block design test, and critical flicker frequency (CFF) testing with a cut-off score of <39Hz. Methodologic assessment of studies was performed using Cochrane Collaboration Risk of Bias Tool and Review Manager (RevMan) version 5.3 for statistical analysis.
 Results. Of the 29 studies identified, 4 fulfilled the inclusion criteria, which entailed analysis of 238 participants (LOLA: 116, Control: 122). Three out of the four studies were used in meta-analysis and one study was analyzed separately due to a difference in the neuropsychometric measure. The metaanalysis favored experimental group (LOLA), with a mean difference of 2.29 (95% CI 0.72 – 3.86), p-value = 0.004, and an I2 of 18%.
 Conclusion. LOLA provided great potential in managing encephalopathy since treating earlier related to better survival and prevention of disease progression. The results of our study supported such evidence and its use may be encouraged.

Probiotics in management of hepatic encephalopathy.

Gut microflora leads to production of ammonia and endotoxins which play important role in the pathogenesis of hepatic encephalopathy (HE). There is relationship between HE and absorption of nitrogenous substances from the intestines. Probiotics play a role in treatment of HE by causing alterations in gut flora by decreasing the counts of pathogen bacteria, intestinal mucosal acidification, decrease in production and absorption of ammonia, alterations in permeability of gut, decreased endotoxin levels and changes in production of short chain fatty acids. Role of gut microbiota using prebiotics, probiotics and synbiotics have been evaluated in the management of minimal hepatic encephalopathy (MHE), overt HE and prevention of HE. Many studies have shown efficacy of probiotics in reduction of blood ammonia levels, treatment of MHE and prevention of HE. However these trials have problems like inclusion of small number of patients, short treatment durations, variability in HE/MHE related outcomes utilized and high bias risk, errors of systematic and random types. Systematic reviews also have shown different results with one systematic review showing clinical benefits whereas another concluded that probiotics do not have any role in treatment of MHE or HE. Also practical questions on optimal dose, ideal combination of organisms, and duration of treatment and persistence of benefits on long term follow-up are still to be clarified. At present, there are no recommendations for use of probiotics in patients with HE.

How to diagnose and manage hepatic encephalopathy

IntroductionHepatic encephalopathy is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting. Symptoms include nonspecific cognitive impairment, personality changes and changes in consciousness. Overt (symptomatic) hepatic encephalopathy is a common complication of cirrhosis that is associated with a poor prognosis. Patients with hepatic encephalopathy may present to healthcare providers who do not have primary responsibility for management of patients with cirrhosis. Therefore, we developed a series of ‘consensus points’ to provide some guidance on management.MethodsUsing a modified ‘Delphi’ process, consensus statements were developed that summarize our recommendations for the diagnosis and management of patients with hepatic encephalopathy. Points on which full consensus could not be reached are also discussed.ResultsOur recommendations emphasize the role of all healthcare providers in the identification of cognitive impairment in patients with cirrhosis and provide guidance on steps that might be considered to make a diagnosis of overt hepatic encephalopathy. In addition, treatment recommendations are summarized. Minimal hepatic encephalopathy can have a significant impact on patients; however, in most circumstances identification and management of minimal hepatic encephalopathy remains the responsibility of specialists in liver diseases.ConclusionOur opinion statements aim to define the roles and responsibilities of all healthcare providers who at times care for patients with cirrhosis and hepatic encephalopathy. We suggest that these recommendations be considered further by colleagues in other disciplines and hope that future guidelines consider the management of patients with cirrhosis and with a ‘suspicion’ of cognitive impairment through to a formal diagnosis of hepatic encephalopathy.

The role of Helicobacter pylori in minimal hepatic encephalopathy

Background One of the causes of death in patients with liver cirrhosis is hepatic encephalopathy (HE). Hyperammonemia is the most important cause of HE. Aim The aim of this work was to determine the relation between the Helicobacter pylori infection and minimal hepatic encephalopathy (MHE) in cirrhotic patients and to assess the outcome after treatment of H. pylori . Patients and methods This study was carried out on 50 Egyptian cirrhotic patients. The patients were divided into two groups: group A1 (32 positive H. pylori ) and group A2 (18 negative H. pylori ). Both groups were compared with 20 (age and sex matched) healthy individuals (group B). Patients and controls were subjected to an assessment of history, clinical examination, upper gastrointestinal endoscopy with gastric biopsy for histopathological examination of H. pylori , abdominal ultrasound, neuropsychiatric assessment using the figure connection test (FCT), complete blood count, liver and kidney function tests, and determination of plasma ammonia level. Plasma ammonia level and FCT were measured before and after treatment of H. pylori among patients with positive H. pylori . Results Plasma ammonia levels and FCT were highly significantly increased in all cirrhotic patients (group A) compared with the controls (group B) ( P H. pylori patients (group A1) compared with the negative H. pylori patients (group A2) ( P P Conclusions There is a highly significant association between H. pylori infection and MHE in cirrhotic patients. The treatment of H. pylori infection reduces the mean plasma ammonia levels and improves FCT results among the infected patients. Therefore, H. pylori infection is an effective treatable risk factor for the clinical management of MHE.

Role of Synbiotic [Bifilac™ <I>Hp</I>] in the Management of Minimal Hepatic Encephalopathy

The aim of the study was to evaluate the efficacy and tolerability of synbiotic [BifilacTM hp] capsules as add on therapy in minimal hepatic encephalopathy [MHE] patients as assessed by cognitive state, serum ammonia level and liver function test. 60 subjects aged between 20 and 50 years were enrolled and randomized into two groups. One group received standard therapy alone and the other group received synbiotic [BifilacTM hp] along with standard therapy. The subjects were assessed using cognitive tests and blood investigation reports. Synbiotic [BifilacTM hp] therapy group showed statistically significant decrease in time needed to complete both the cognitive assessment tests i.e., Number Connection Test [NCT] and Line Tracing Test [LTT] when compared to the standard treatment group. Significant reduction in serum ammonia and hepatic enzymes level were also observed. BifilacTM hp when added to standard therapy is found to be more beneficial than the standard therapy alone in the management of minimal hepatic encephalopathy.

Optimal medical management of minimal hepatic encephalopathy: a systematic review protocol

Review question/objective The purpose of this systematic review is to present the best available evidence for the use of disaccharides versus no treatment in the medical management of minimal hepatic encephalopathy. The objectives of this review are to identify effective medical management strategies for the prevention of minimal hepatic encephalopathy (MHE) and also minimize the adverse clinical manifestations of minimal hepatic encephalopathy. Inclusion criteria Types of participants Studies of adult patients, 18 years and older, with the diagnosis of minimal hepatic encephalopathy in both ambulatory and acute care hospital settings will be included in the review. Transplant patients and patients who have undergone transjugular intrahepatic portosystemic shunt (TIPS) will be excluded. Patients undergoing liver dialysis procedures will also be excluded as they may have other comorbidities that affect their overall treatment plan. Pregnant women will also be excluded in the search. Types of intervention(s) This review will consider studies that evaluate optimal medical management of minimal hepatic encephalopathy strategies. The interventions of interest will be the use of disaccharides to manage the patient with minimal hepatic encephalopathy. Types of outcomes This review will consider studies that include the following outcome measures: psychometric measures, health-related quality of life measures and motor skills. More specifically these include outcomes associated with general care strategies: nutrition, hydration and electrolyte status, as well as safety (due to neuro-cognitive indicators), and in acute illness will measure prevention of coma (lowered blood ammonia levels).

Probiotics in Minimal Hepatic Encephalopathy: A Meta-Analysis

Purpose: Minimal hepatic encephalopathy (MHE) is characterized by abnormal neurophysiological testing and absence of clinical symptoms. Attention span and reaction time are reduced, with impaired quality of life and reduced survival. Elevated ammonia is implicated in the pathophysiology; treatment options are directed at lowering it. Probiotics are live microorganisms, beneficial to the host in therapeutic doses. They prevent the proliferation of pathogenic bacteria in the GI tract and hence decrease ammonia production. Several studies have been conducted to identify its role in the management of MHE with variable results. We herein perform a meta-analysis of these studies. Methods: We performed a search on Pubmed and Medview to identify randomized controlled trials (RCT) on probiotics in MHE in the last 20 years. To be eligible, studies had to include at least two randomized groups with a pre post comparison of mean ± standard deviation of serum ammonia levels. Five studies comparing probiotics vs placebo/no treatment and three studies comparing probiotics vs lactulose were included. Analyses were done using Comprehensive Met Analysis 2.2 (Biostat, Englewood, NJ).Figure: [362] Statistical analysis of probiotics vs placebo in MHE.Figure: [362] Statistical analysis of probiotics vs lactulose in MHE.Results: On comparing probiotics with placebo, treatment with probiotics was superior to placebo or no treatment (p=0.006) and to lactulose (p=0.02). The standardized difference (95 % CI) for probiotics vs placebo was 0.44 (0.13, 0.75) while probiotics vs lactulose was 0.32 (0.06, 0.58). Conclusion: The results of the two meta-analyses described above indicate the beneficial role of probiotics in lowering serum ammonia levels in MHE patients. These results compare favorably with lactulose, with possibly fewer adverse effects such as diarrhea and bloating. Large RCT studies are warranted to further validate the role of probiotics in MHE.

Clinical efficacy and safety of lactulose for minimal hepatic encephalopathy

To evaluate the clinical efficacy of lactulose in patients with minimal hepatic encephalopathy (MHE). Randomized controlled trials (RCTs) comparing lactulose with placebo or with no intervention in the management of MHE that were conducted from January 1990 to July 2011 were searched from MEDLINE, EMBASE, SCI, Cochrane Controlled Trials Register, and China Biological Medicine Database. Studies with a Jadad score higher than 3 were included in the meta-analysis and evaluated using RevMan5.0 software for relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (95% CI). Sensitivity analysis was performed on the ethnical differences and quality of the trials. Publication bias was observed using an inverted funnel plot. Nine studies with 434 patients were included in the meta-analysis. Compared with placebo or no intervention, lactulose significantly reduced the risk of no improvement in neuropsychological tests (RR: 0.52, 95% CI: 0.44-0.62, P<0.00001), the time required for the completion of the number connection test-A (WMD: -26.95, 95% CI: -37.81 to -16.10, P<0.00001), and the mean number of abnormal neuropsychological tests (WMD: -1.76, 95% CI: -1.96 to -1.56, P<0.00001). Furthermore, the meta-analysis also showed that lactulose prevented the progression to overt hepatic encephalopathy (RR: 0.17, 95% CI: 0.06-0.52, P=0.002), reduced blood ammonia levels (WMD: -9.89 µmol/l, 95% CI: -11.01 to -8.77 µmol/l, P<0.00001), and improve health-related quality of life (WMD: -6.05, 95% CI: -6.30 to -5.20, P<0.00001). However, no significant difference was observed in the mortality of patients with MHE (RR: 0.75, 95% CI: 0.21-2.72, P=0.66), and lactulose significantly increased the incidence of diarrhea (RR: 4.38, 95% CI: 1.35-14.25, P=0.01). Lactulose has significant beneficial effects for patients with MHE compared with placebo or no intervention.

Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is characterised by subtle neurocognitive deficits without overt clinical manifestations. Although several trials have individually evaluated the role of prebiotics, probiotics and synbiotics, there is yet no consensus on the management of MHE. To estimate the efficacy of prebiotics, probiotics and synbiotics in MHE in randomised controlled trials. MEDLINE, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews were searched for published studies in all languages. Inclusion and exclusion criteria were defined a priori. Pooled relative risk and heterogeneity were estimated as the measures of association. Nine studies met our inclusion criteria. Use of prebiotics, probiotics and synbiotics significantly reduced the pooled relative risk (RR) of no improvement of MHE (RR 0.40, 95% CI 0.32-0.50; P<0.001). Upon subgroup analysis, five studies with lactulose showed significant reduction of risk of no improvement of MHE (RR 0.34, 95% CI 0.24-0.47; P<0.0001) with no inter-trial heterogeneity. In two trials each of probiotics and synbiotics, their use was associated with significant beneficial effects (RR 0.41, 95% CI 0.26-0.65; P<0.0001 and RR of 0.51, 95% CI 0.32-0.80; P=0.004 respectively). There were no major adverse events though probiotics and synbiotics were better tolerated than lactulose. The use of prebiotics, probiotics and synbiotics was associated with significant improvement in minimal hepatic encephalopathy. Among individual agents, lactulose appears to have the most beneficial effect, followed closely by probiotics and synbiotics.

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.