Encephalopathy Index Research Articles

Efficacy and Safety of Rifaximin Versus Placebo or Other Active Drugs in Critical ill Patients With Hepatic Encephalopathy.

Objective: Rifaximin has been approved for use as a first-line therapy for secondary prophylaxis of hepatic encephalopathy (HE). This article is to update existing evidence on efficacy and safety of rifaximin treatment and prevention for HE. Methods: We systematically searched multiple databases until January 31 2021. The studies compared rifaximin vs. placebo or other active drugs (i.e., nonabsorbable disaccharides, other antibiotics, L-ornithine-L-aspartate (LOLA), and probiotics) for patients with overt HE (OHE), minimal HE (MHE), and recurrent HE. Results: Twenty-eight randomized controlled trials with a total of 2979 patients were included. Compared with the controls, rifaximin significantly reduced HE grade (OHE: RR = 1.11, 95% CI = 1.02–1.21), improved the cognitive impairments (MHE: RR = 1.82, 95% CI = 1.12–2.93) and prevented the risk of HE recurrent episodes (RR = 1.33, 95% CI = 1.18–1.49). No statistical difference was observed in mortality between rifaximin and their controls (RR = 0.82, 95% CI = 0.54–1.24). The incidence of total adverse events in rifaximin-treated groups was significantly lower than that in the controls during the treatment period (RR = 0.73, 95% CI = 0.54–0.98). In addition, rifaximin treatment was better than other active drugs in improving psychometric indicators (mental state, flapping tremor and portosystemic encephalopathy (PSE) index) and reducing the risk of rehospitalization in HE patients. Conclusion: Rifaximin therapy is effective and well-tolerated in different types of HE, which might be recommended as an alternative to conventional oral drugs in clinical settings.

Additional L-Carnitine Reduced the Risk of Hospitalization in Patients with Overt Hepatic Encephalopathy on Rifaximin

Background: Data regarding the additional effect on the recurrence of hepatic encephalopathy (HE) after oral L-carnitine administration are scarce. Objective: This study aimed to assess the additional effects of L-carnitine in patients who were receiving rifaximin for HE. Methods: This randomized study comprised a screening visit and a 12-week treatment period. Patients who fulfilled the eligibility criteria were randomized to either group A (additional rifaximin) or group B (additional L-carnitine and rifaximin). Group A received 1,200 mg/day of rifaximin. Group B received 1,500 mg/day of L-carnitine and rifaximin at 1,200 mg/day. The endpoints were the changes in the portal systemic encephalopathy (PSE) index and the admission rate from the baseline for the duration of the study in both groups. Results: Eighty-three patients were randomized to either group A (n = 42) or group B (n = 41). In group A, the PSE index decreased from 0.35 ± 0.09 at baseline to 0.27 ± 0.11 on the final evaluation day (p = 0.001). In group B, the PSE index decreased from 0.37 ± 0.09 at baseline to 0.24 ± 0.11 on the final evaluation day (p = 0.001). Although there was not a significant reduction in the PSE index in group A compared to that in group B (p = 0.202), the admission rates were 30.9% and 9.8% in groups A and B, respectively. Additional L-carnitine significantly reduced the admission rate (p = 0.028). Conclusion: L-Carnitine addition reduced the risk of hospitalization for patients who received rifaximin for HE.

Bioartificial liver support systems for acute liver failure: A systematic review and meta-analysis of the clinical and preclinical literature.

BACKGROUNDAcute liver failure (ALF) has a high mortality varying from 80% to 85% with rapid progress in multi-organ system failure. Bioartificial liver (BAL) support systems have the potential to provide temporary support to bridge patients with ALF to liver transplantation or spontaneous recovery. In the past decades, several BAL support systems have been conducted in clinical trials. More recently, concerns have been raised on the renovation of high-quality cell sources and configuration of BAL support systems to provide more benefits to ALF models in preclinical experiments.AIMTo investigate the characteristics of studies about BAL support systems for ALF, and to evaluate their effects on mortality.METHODSEligible clinical trials and preclinical experiments on large animals were identified on Cochrane Library, PubMed, and EMbase up to March 6, 2019. Two reviewers independently extracted the necessary information, including key BAL indicators, survival and indicating outcomes, and adverse events during treatment. Descriptive analysis was used to identify the characteristics of the included studies, and a meta-analysis including only randomized controlled trial (RCT) studies was done to calculate the overall effect of BAL on mortality among humans and large animals, respectively.RESULTSOf the 30 selected studies, 18 were clinical trials and 12 were preclinical experiments. The meta-analysis result suggested that BAL might reduce mortality in ALF in large animals, probably due to the recent improvement of BAL, including the type, cell source, cell mass, and bioreactor, but seemed ineffective for humans [BAL vs control: relative risk (95% confidence interval), 0.27 (0.12-0.62) for animals and 0.72 (0.48-1.08) for humans]. Liver and renal functions, hematologic and coagulative parameters, encephalopathy index, and neurological indicators seemed to improve after BAL, with neither meaningful adverse events nor porcine endogenous retrovirus infection.CONCLUSIONBAL may reduce the mortality of ALF by bridging the gap between preclinical experiments and clinical trials. Clinical trials using improved BAL must be designed scientifically and conducted in the future to provide evidence for transformation.

Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial.

The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia.

Role of Rifaximin for the Treatment of Hepatic Encephalopathy in Chronic Liver Disease

Background: Hepatic encephalopathy (HE) is a common problem in patients with chronic liver disease (CLD) and is characterized by diminished mentation and neuromuscular abnormalities. Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe and other countries. It is unknown whether rifaximin is effective for the treatment of hepatic encephalopathy in Bangladeshi patients.Methods: A prospective, randomized, single blind, placebo controlled study was conducted to evaluate the efficacy of rifaximin among patients with cirrhosis of liver with hepatic encephalopathy. A total sixty patients of HE fulfilling inclusion criteria were randomly enrolled among those admitted under Gastrointestinal, Hepatobiliary and Pancreatic Disorders (GHPD) department of BIRDEM General Hospital during August 2012 to April 2013. Patients were divided into two groups: group A (receiving Tab. rifaximin with lactulose), the total number of patients were 31(51.7%) and group B (receiving placebo with lactulose), it was 29(48.3%). Enrolled patients were followed up for 10 days or up to discharge from the hospital or death. At enrollment and at the end of treatment, gradation of HE and estimation of portosystemic encephalopathy (PSE) index was done.Results: In this study between two groups, mean age difference (p=0.404), gender difference (p=0.668) and CLD duration difference (p=0.555) were not statistically significant between two groups. At enrollment, prognostic scores e.g. Child-Turcotte-Pugh (CTP) score (p=0.489) and PSE index (p=0.934) were not significantly different between two groups. At the end of treatment, group A patients showed significantly lower HE grade (P=0.045) and PSE index (P<0.05) than group B. CTP score (p=0.552) was also lower in rifaximin treated group than placebo group but no significant difference was observed. The mean duration of hospital stay was significantly lower in group A than group B (p<0.05).Conclusions: Hepatic encephalopathy patients treated with rifaximin plus lactulose have better outcome and less hospital stay than those treated with placebo plus lactulose.Birdem Med J 2017; 7(3): 205-211

Relationship between clock and star drawing and the degree of hepatic encephalopathy

Purpose of the studyCurrent hepatic encephalopathy grading tools are limited because of complexity or subjectivity. The degree of constructional apraxia could serve as a simple, objective and reproducible tool to...

Current and future diagnosis of hepatic encephalopathy

This short communication is based on the lecture given by the author entitled “Current and Future Diagnosis of Hepatic Encephalopathy” at the 5th Hannover International Conference on Hepatic Encephalopathy held in Mainz, Germany in May 2009. The presentation was based on published literature and abstracts and involved a concise review of currently available strategies to diagnose hepatic encephalopathy (HE). The talk started with an overview of the clinical scales that are currently used to diagnose HE (Ferenci et al. 2002). Clinical methods that were discussed were the West-Haven Scale, the Hepatic Encephalopathy Scoring Algorithm (HESA), the Clinical Hepatic Encephalopathy Staging Scale (CHESS) and the Porto-Systemic Encephalopathy (PSE) index (Conn et al. 1977, Teasdale and Jennett 1974, Blei and Cordoba 2001, Hassanein et al. 2008, 2009). The standard currently used is the West-Haven scale that divides patients with HE from stages 0 through 4 (Teasdale and Jennett 1974). Stage 4 is coma while stage 0 is technically “normal”. Stage 1 is characterized by “trivial lack of awareness, euphoria or anxiety, shortened attention span and impairment of addition or subtraction” while stage 2 onwards, disorientation starts. The West Haven scale has been criticized for its subjectivity, especially in the initial stages of 0 through 2. Specifically, there is little agreement between observers at different centers regarding their interpretation of HE grade using the West-Haven criteria alone (Hassanein et al. 2009). This subjective nature is also difficult to overcome while designing and interpreting HE trials that are conducted on a multi-center basis. This led to an overview of the CHESS, which is a simple 9-question scale used to characterize orientation and current awareness that is still undergoing validation (Ortiz et al. 2007). The PSE index and HESA were discussed briefly as scales that blend clinical and psychometric/neurophysiologic measures. The PSE index, consisting of clinical assessment, EEG, arterial ammonia, trail-making test time and asterixis, has not been used widely since its components are inter-related and not specific (Ferenci et al. 2002). The HESA, is a blended scale consisting of clinical evaluation of the mental status and neuropsychological parameters. It seeks to improve upon the West-Haven criteria by dividing HE into four grades with the neuropsychological assessment in addition to the pure clinical assessment as in the West-Haven Scale (Hassanein et al. 2008, 2009). The psychometric tests used are simple, such as computations, construction ability and memory (Hassanein et al. 2009). The role of HESA is evolving and it needs further validation. A brief mention was made of asterixis as a physical finding in HE and the lack of specificity and sensitivity of this clinical finding alone (Ferenci et al. 2002). The presence of asterixis in renal failure and carbon dioxide narcosis and its absence in early and very advanced HE was highlighted. The specialized tests currently available for HE were then presented under the broad headings of psychometric and neuro-physiologic tests (Ferenci et al. 2002).

Rifaximin for Treatment of Hepatic Encephalopathy

To review the effectiveness and safety of rifaximin in the treatment of hepatic encephalopathy (HE). MEDLINE (1990-October 2008) was searched using the terms rifaximin, rifamycins, hepatic encephalopathy, liver cirrhosis, and acute liver failure. Other sources included the bibliographies of pertinent articles as well as programs and abstracts from infectious diseases and gastrointestinal diseases meetings. All English-language articles identified from the search were evaluated. All primary literature that addressed the efficacy and safety of rifaximin in the treatment of HE was included in this review. HE is a complex neuropsychiatric syndrome seen in patients with liver failure. It is characterized by disturbances in consciousness and behavior, personality changes, fluctuating neurologic signs, asterixis, and electroencephalographic changes. Although the etiology of HE is unknown, the accumulation of several gut-derived toxins such as mercaptans, ammonia, and benzodiazepine has been implicated. Current treatment options for HE include agents that reduce the concentration of these toxins, such as nonabsorbable disaccharides and antibiotics. Several studies have evaluated the use of rifaximin in the treatment of HE. They include a dose-finding study, 9 open-label studies, and 4 double-blind studies comparing rifaximin with either nonabsorbable disaccharides or antibiotics. Commonly used outcomes in most of these studies were changes in portal systemic encephalopathy index and the improvement in HE grade. Despite various limitations of the studies, rifaximin showed superior efficacy compared with lactulose for the treatment of HE, similar efficacy to paromomycin, and similar or greater efficacy than neomycin. Rifaximin was found to be associated with fewer hospitalizations, fewer days of hospitalization, and lower hospitalization charges than were seen with lactulose. Rifaximin also had a better tolerance profile than the comparative agents. Rifaximin appears to be an effective and safe treatment option for HE. Better-designed studies are needed to characterize its efficacy in the treatment of HE.

Clinical effects of rifaximin in patientswith hepatic encephalopathy intolerant or nonresponsive to previous lactulose treatment: An open-label, pilot study

Background: Hepatic encephalopathy (HE) is a metabolic-neurophysiologicsyndrome that occurs in patients with advanced hepatic disease. One of the main pathogenic mechanisms is represented by circulating toxins produced by the intestinal metabolism of nitrogenous compounds. The therapeutic approach to HE is mainly based on drugs that eliminate ammonia-producing bacteria. Objectives: The aim of this study was to evaluate the effects of the nonabsorbable antibiotic rifaximin in patients with HE who were intolerant or nonresponsive to treatment with an oral, nonabsorbable disaccharide (lactulose). Methods: This uncontrolled, open-label, pilot study was conducted at the University of Bologna, Bologna, Italy. Patients aged ≥ 18 years with histologically proven liver cirrhosis and HE were studied. All patients were intolerant or nonresponsive to previous treatment with lactulose. Rifaximin tablets were administered to patients at a dosage of 400 mg TID for 10 days. The portal systemic encephalopathy (PSE) index was evaluated at enrollment and at the end of the treatment period. Tolerability was assessed using hematology, biochemistry, and urinalysis and by recording adverse effects (AEs). Results: Twenty-six patients (18 men, 8 women; mean [SD] age, 55.8 [8.0] years) were enrolled (intolerants, n = 17; nonresponders, n = 9). All patients completed the study. Significant improvement was shown in most of the 5 components of the PSE index after rifaximin administration in both intolerants and nonresponders. At the end of the 10-day treatment period, the PSE index was significantly reduced in both intolerants and nonresponders. Rifaximin was well tolerated; no clinically relevant AEs were observed during the treatment period. Conclusions: This pilot study of patients with liver cirrhosis and HE who were intolerant or nonresponsive to previous treatment with an oral, nonabsorbable disaccharide suggests that treatment with rifaximin may be considered as an adjuvant or an alternative treatment in reducing HE.

Charcoal-based hemodiabsorption liver support for episodic type C hepatic encephalopathy.

Episodic (acute) type C hepatic encephalopathy (AHE) fails to respond to 5 days of medical therapy in 10-30% of patients and carries a 10-30% mortality rate. We prospectively studied extracorporeal liver support for AHE failing to respond to medical therapy to assess its safety and efficacy and the role of anticoagulation. A series of patients with cirrhosis and AHE failing to respond to at least 24 h of medical therapy underwent a maximum of three 6-h charcoal-based hemodiabsorption (Liver Dialysis Unit) treatments. A standard anticoagulation protocol, with heparin dosing based on activated clotting time (ACT) determinations, heparin dose-response curve, and target ACT of 275-300 s, was developed. Therapy was terminated if patients met a predetermined clinical response, deteriorated, or underwent transplantation. Eighteen patients with grade 2-4 AHE despite 5.9 +/- 3.9 days of medical therapy underwent a mean of 1.6 treatments. In 2.6 +/- 1.9 days, 16 patients (88.9%) improved to less than grade 2 HE or achieved at least a 50% hepatic encephalopathy index (HEI) reduction. Median mental status (grade 2 vs 1, p < 0.05) and HEI (0.634 +/- 0.194 vs 0.363 +/- 0.263, p < 0.005) improved significantly. Survival was 94.4% and 72.2% at 5 and 30 days, respectively. Use of our developed anticoagulation protocol resulted in less platelet (14.2% +/- 2.8% vs 32.5% +/- 5.8%, p < 0.005) and fibrinogen consumption (12.1% +/- 3.5% vs 43.3% +/- 8.6%, p < 0.0005) and blood product use (6.2 +/- 1.8 vs 19.0 +/- 5.6 units, p < 0.05) compared with treatments according to manufacturer's guidelines. Charcoal-based hemodiabsorption treatments in which a standardized anticoagulation protocol is used is safe and effective treatment for AHE not responding to standard medical therapy.

Charcoal-based hemodiabsorption liver support for episodic type C hepatic encephalopathy

Objectives Episodic (acute) type C hepatic encephalopathy (AHE) fails to respond to 5 days of medical therapy in 10–30% of patients and carries a 10–30% mortality rate. We prospectively studied extracorporeal liver support for AHE failing to respond to medical therapy to assess its safety and efficacy and the role of anticoagulation. Methods A series of patients with cirrhosis and AHE failing to respond to at least 24 h of medical therapy underwent a maximum of three 6-h charcoal-based hemodiabsorption (Liver Dialysis Unit) treatments. A standard anticoagulation protocol, with heparin dosing based on activated clotting time (ACT) determinations, heparin dose–response curve, and target ACT of 275–300 s, was developed. Therapy was terminated if patients met a predetermined clinical response, deteriorated, or underwent transplantation. Results Eighteen patients with grade 2–4 AHE despite 5.9 ± 3.9 days of medical therapy underwent a mean of 1.6 treatments. In 2.6 ± 1.9 days, 16 patients (88.9%) improved to less than grade 2 HE or achieved at least a 50% hepatic encephalopathy index (HEI) reduction. Median mental status (grade 2 vs 1, p < 0.05) and HEI (0.634 ± 0.194 vs 0.363 ± 0.263, p < 0.005) improved significantly. Survival was 94.4% and 72.2% at 5 and 30 days, respectively. Use of our developed anticoagulation protocol resulted in less platelet (14.2% ± 2.8% vs 32.5% ± 5.8%, p < 0.005) and fibrinogen consumption (12.1% ± 3.5% vs 43.3% ± 8.6%, p < 0.0005) and blood product use (6.2 ± 1.8 vs 19.0 ± 5.6 units, p < 0.05) compared with treatments according to manufacturer's guidelines. Conclusions Charcoal-based hemodiabsorption treatments in which a standardized anticoagulation protocol is used is safe and effective treatment for AHE not responding to standard medical therapy.

Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial

Background/Aims: The efficacy and safety of rifaximin in comparison with lactitol in the treatment of acute hepatic encephalopathy was assessed in a prospective randomized, double-blind, double-dummy, controlled trial. Methods: A total of 103 patients with grade I–III acute hepatic encephalopathy were randomized to receive rifaximin (50 patients, 1200 mg/day) or lactitol (53 patients, 60 g/day) for 5–10 days. Changes in the portal-systemic encephalopathy (PSE) index on entry and at the end of the study were used to evaluate the efficacy of the two therapies. Results: Both groups were comparable before treatment with regard to demographic data and characteristics of the hepatic encephalopathy episode. The global efficacy of both therapies was similar: 81.6% in the rifaximin group and 80.4% in the lactitol group showed improvement or total regression of the episode. A significantly better evolution of the PSE index was observed in the rifaximin group, due to a greater effect of rifaximin in two components of the index: EEG abnormalities and ammonia levels. No serious adverse events related to either treatment were found during the study. Conclusions: Rifaximin may be considered a useful and safe alternative therapy to lactitol in the treatment of acute hepatic encephalopathy in cirrhosis.

Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study

Background/Aims: In the current state of knowledge of the pathophysiology of hepatic encephalopathy, a reduction in hyperammonemia is the most important evidence of effective treatment. Therefore, the therapeutic efficacy of oral L-ornithine-L-aspartate, which improves impaired ammonia detoxification, was investigated in patients with cirrhosis, hyperammonemia and stable, overt, chronic hepatic encephalopathy, and in subclinical hepatic encephalopathy in a randomized, double-blind, placebo-controlled clinical trial. Methods: Oral L-ornithine-L-aspartate was administered three times daily at fixed times for 14 consecutive days in a total dose of 18 g per day. The design was chosen to prevent an increase in ammonia induced by a protein meal of 0.25 g/kg body weight, given at the start of the daily treatment period. Efficacy variables were: fasting and postprandial ammonia concentration, Number-Connection-Test time, mental state grades, and a Portosystemic Encephalopathy Index. Analyses were based on the total study sample of 32 placebo- and 34 L-ornithine-L-aspartate-treated patients as well as on the subgroup samples in the overt (20 placebo- and 23 L-ornithine-L-aspartate-treated) and subclinical hepatic encephalopathy (12 placebo- and 11 L-ornithine-L-aspartate-treated) patients. Results: Number Connection Test performance times ( p<0.01) as well as fasting ( p<0.01) and postprandial ( p<0.05) venous blood ammonia concentrations in the L-ornithine-L-aspartate-treated group showed improvement in comparison to placebo. Also, the mental state grade ( p<0.05) and the Portosystemic Encephalopathy Index ( p<0.01), improved to a much greater degree in the L-ornithine-L-aspartate group than in the placebo group. Adverse events were observed in neither the placebo nor the L-ornithine-L-aspartate-treated patients. Conclusion: Oral L-ornithine-L-aspartate is a safe, well-tolerated treatment with a good compliance rate and a beneficial therapeutic effect in patients with cirrhosis and stable, overt, chronic hepatic encephalopathy.

A Bioartificial Liver to Treat Severe Acute Liver Failure

To test the safety and efficacy of a bioartificial liver support system in patients with severe acute liver failure. The authors developed a bioartificial liver using porcine hepatocytes. The system was tested in vitro and shown to have differentiated liver functions (cytochrome P450 activity, synthesis of liver-specific proteins, bilirubin synthesis, and conjugation). When tested in vivo in experimental animals with liver failure, it gave substantial metabolic and hemodynamic support. Seven patients with severe acute liver failure received a double lumen catheter in the saphenous vein; blood was removed, plasma was separated and perfused through a cartridge containing 4 to 6 x 10(9) porcine hepatocytes, and plasma and blood cells were reconstituted and reinfused. Each treatment lasted 6 to 7 hours. All patients tolerated the procedure(s) well, with neurologic improvement, decreased intracranial pressure (23.0 +/- 2.3 to 7.8 +/- 1.7 mm Hg; p < 0.005) associated with an increase in cerebral perfusion pressure, decreased plasma ammonia (163.3 +/- 21.3 to 112.2 +/- 9.8 microMoles/L; p < 0.01), and increased encephalopathy index (0.60 +/- 0.17 to 1.24 +/- 0.22; p < 0.03). All patients survived, had a liver transplant, and were discharged from the hospital. This bioartificial liver is safe and serves as an effective "bridge" to liver transplant in some patients.

Effects of long-term administration of low-dose lactitol in patients with cirrhosis but without overt encephalopathy

To investigate the efficacy and the acceptability of different doses of lactitol in patients with subclinical hepatic encephalopathy, 28 patients with cirrhosis were enrolled in a controlled clinical trial comparing 5-month therapies with lactitol at two different doses: 0.3 and 0.5 g/kg bw per day. This period was followed by 1 month of recovery. Patients were monitored with venous blood ammonia determination, three psychometric tests, clinical evaluation of mental status and EEG. The porto-systemic encephalopathy index of Conn was determined periodically. Twenty-two patients completed the trial (11 for each dose of lactitol). Both doses of lactitol decreased plasma ammonia levels and improved the porto-systemic encephalopathy index. The higher dose was more effective in improving performance in the psychometric tests. After the period of recovery, both the porto-systemic encephalopathy index and the psychometric test scores returned to pretreatment values. Lactitol was tolerated well by patients. Three patients given the higher dose reported periodic intestinal discomfort, but did not stop taking lactitol or reduce the dosage; no side-effects were reported by the patients taking the lower dose. These results indicate that lactitol in doses ranging from 0.3 to 0.5 g/kg bw is a well-tolerated and effective treatment for subclinical encephalopathy.

Lactitol or lactulose in the treatment of chronic hepatic encephalopathy: results of a meta-analysis.

Lactitol (beta-galactosido-sorbitol) has been recently compared with lactulose for the treatment of chronic hepatic encephalopathy in a few studies, each comprising a small number of patients. The results are controversial. We studied the efficiency and tolerance of both compounds by using a meta-analysis on the basis of published controlled trials. Our study only included controlled or randomized trials comprising cirrhotic patients with chronic hepatic encephalopathy. Analyzed parameters were the portosystemic encephalopathy index of Conn after treatment, the percentage of improved patients and the percentage of patients who had ill effects related to the treatment (flatulence, diarrhea). Bibliographical screening revealed five studies comparing the effects of lactitol and lactulose in chronic hepatic encephalopathy. Four crossover studies were done that included 48 patients and one parallel study that included 29 patients. The duration of the treatment ranged from 3 to 6 mo. All studies found a similar efficiency with both drugs. However, they exhibited some discrepancies in the relative frequency of adverse reactions (flatulence). Meta-analysis showed no statistical differences in the portosystemic encephalopathy index after lactitol or lactulose treatment. The percentage of improved patients after lactitol or lactulose was similar. In contrast, the analysis revealed a higher frequency (p less than 0.01) of flatulence in patients treated with lactulose compared with those treated with lactitol. In conclusion, this meta-analysis shows no statistical difference between therapeutic effects of lactitol and lactulose, but it does show a higher frequency of flatulence with lactulose. This suggests that lactitol should be preferred to lactulose for the treatment of chronic hepatic encephalopathy.

Enriched Branched‐Chain Amino Acid Formula Versus a Casein‐Based Supplement in the Treatment of Cirrhosis

An orally administered branched-chain amino acid (BCAA) rich supplement (T), Travasorb-Hepatic was compared to a casein based supplement (E), Ensure, in a randomized double-blind cross-over study in eight malnourished, stable cirrhotics unable to achieve a daily dietary protein intake of 1.0 g/kg. Doses of antiportal systemic encephalopathy drugs remained constant and a baseline 1000 kcal, 40 g dietary protein intake was encouraged. To this diet, supplemental protein was added in daily 20-g increments to a maximum of 60 g supplemental protein. Mental status, asterixis, and number connection tests were assessed daily and an antiportal systemic encephalopathy index calculated. There was no significant difference in the mean intake of dietary protein (T, 33.7 +/- 4.0 g; E, 26.7 +/- 10.8 g), supplemental protein (T, 43.1 +/- 8.3 g; E, 47.9 +/- 7.1 g), or N2 balance (T, 4.2 +/- 3.7 g; E, 3.4 +/- 4.4) between treatment trials. The antiportal systemic encephalopathy index improved on E, with no significant change in the BCAA:aromatic acid molar ratio. This ratio improved on T (1.02 +/- 2.0 to 2.7 +/- 1.1), but was not accompanied by improvement in the antiportal systemic encephalopathy index. The improved protein tolerance in both groups was not further increased by a highly enriched BCAA formula compared to one with a moderate BCAA content from a natural dietary protein source. Thus, both conventional casein-based supplements and enriched BCAA formulas are well tolerated and can be safely and effectively used as an integral part of diet therapy.

Effect of vegetable and animal protein diets in chronic hepatic encephalopathy

In the present investigation, studies were carried out to examine the effect of a vegetable-protein diet as compared to an animal-protein diet on standard clinical and laboratory parameters in 3 patients with chronic hepatic encephalopathy. To evaluate more objectively the effects of vegetable or animal protein diets, an hepatic encephalopathy index was developed, and this included the following parameters: fetor hepaticus, asterixis, stage of hepatic coma (Parson-Smith), arterial ammonia levels, EEG, Reitan trail test, and any reduction or improvement in dietary protein tolerance. In controlled, randomized, single-blind trials, it was found that a vegetable-protein diet resulted in overall clinical improvement, decreased hepatic encephalopathy index scores, decreased arterial ammonia levels, improved performance on intellectual tasks, and in one case, markedly improved protein tolerance. Further, the beneficial effects of a vegetable-protein diet were enhanced by the use of the synthetic disaccharide, lactulose. These studies do not provide a clear-cut definition of the mechanism for the observed beneficial effects of vegetable protein in chronic hepatic encephalopathy. However, the most plausible explanation is that vegetable-protein diets contain lower amounts of certain amino acids and other putative materials which may be important in the pathogenesis of hepatic encephalopathy.