Amino Acids In Hepatic Encephalopathy Research Articles

Branched chain amino acids in hepatic encephalopathy and sarcopenia in liver cirrhosis: Evidence and uncertainties.

Liver cirrhosis is commonly associated with nutritional alterations, reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis. Nutritional disturbances are associated with a worse prognosis and increased risk of complication. Serum levels of branched-chain amino acids (BCAAs) are decreased in patients with liver cirrhosis. The imbalance of amino acids levels has been suggested to be associated with the development of complications, such as hepatic encephalopathy and sarcopenia, and to affect the clinical presentation and prognosis of these patients. Several studies investigated the efficacy of BCAAs supplementation as a therapeutic option in liver cirrhosis, but uncertainties remain about the real efficacy, the best route of administration, and dosage.

Intravenous Branched Chain Amino Acids for Hepatic Encephalopathy in ACLF

Intravenous Branched Chain Amino Acids for Hepatic Encephalopathy in ACLF

P: 59 Supplementation With Synbiotics and/or Branched Chain Amino Acids in Hepatic Encephalopathy: A Pilot Randomised Placebo-Controlled Clinical Study

BACKGROUND: Hepatic encephalopathy (HE) is common in patients with cirrhosis and characterised by reduced hepatic ammonia clearance. This is accompanied by alterations in gut bacteria and increased intestinal epithelial permeability that may be ameliorated with synbiotics (pro- and pre-biotics). Branched chain amino acids (BCAAs) are thought to have a role in the detoxification of ammonia. We investigated the effects of the administration of Synbiotics and/or BCAAs in treating HE. METHODS: Methods Participants with minimal HE (MHE) were randomised in an placebo-controlled study to receive synbiotics, BCAAs, or a combination of BCAAs and Synbiotics. The investigators were blinded to the supplements at all times. Relevant biochemical and nutritional data and depression and anxiety scores (DASS-21) were collected at entry, 4 weeks, and on completion, at 8 weeks. The Trail Making Test (TMT) and Inhibitory Control Test (ICT) were used to assess cognitive function in HE. Results were analysed using linear mixed effects regression analyses RESULTS: Sixty-one participants with MHE determined by the treating physician, confirmed on psychometric testing (TMT and ICT) and who were taking 63 ± 6 mLs lactulose/day were enrolled. Recruitment was limited by the widespread introduction of rifaximin in Australia during the recruitment period. The final intention to treat analysis included 49 participants who returned for at least 1 follow-up review. The mean age was 55.8 ± 6.1 years and 86% were males. Despite evidence of a placebo effect, there was significant improvement in TMT B (P ≤ 0.05) (Figure 1a) and ICT weighted lures (P = 0.007) (Figure 1b) in participants who received combined synbiotics/BCAAs treatment compared to placebo at study completion. Cognitive improvement occurred without a significant change in ammonia levels. CONCLUSIONS: To the best of our knowledge, this study is the first to report an improvement in cognitive function and, therefore, executive function in individuals with decompensated cirrhosis and MHE in response to oral supplementation with combined synbiotics and BCAAs. A larger study which includes measures of dysbiosis and intestinal epithelial permeability is needed to confirm these results.

Supplementation with Synbiotics and/or Branched Chain Amino Acids in Hepatic Encephalopathy: A Pilot Randomised Placebo-Controlled Clinical Study.

Introduction: Hepatic encephalopathy (HE) is common in patients with cirrhosis and is characterised by reduced hepatic ammonia clearance. This is accompanied by alterations in gut bacteria that may be ameliorated with synbiotics (pro- and prebiotics). Branched chain amino acids (BCAAs) are thought to have a role in the detoxification of ammonia. We investigated the effects of the administration of synbiotics and/or BCAAs in treating HE. Methods: Participants with overt HE were randomised in a blinded placebo-controlled study to receive synbiotics, BCAAs, or a combination of BCAAs and Synbiotics. Relevant biochemical and nutritional data and depression and anxiety scores (DASS-21) were collected at entry, 4 weeks, and on completion, at 8 weeks. The Trail Making Test (TMT) and Inhibitory Control Test (ICT) were used to assess cognitive function in patients withHE. Results were analysed using linear mixed effects regression analyses. Results: Sixty-one participants were enrolled and 49 who returned for at least 1 follow-up review were included in the intention to treat analysis. The mean age was 55.8 ± 6.1 years and 86% were males. Despite evidence of a placebo effect, there was significant improvement in TMT B and ICT weighted lures in participants who received combined synbiotics/BCAAs treatment compared to placebo at study completion (p ≤ 0.05). Cognitive improvement occurred without a significant change in ammonia levels. Conclusion: To our knowledge, this is the first study reporting that combined synbiotics and BCAAs improve HE, and that may be beneficial in the management of HE. A larger study is needed to confirm these results.

Role of Branched Chain Amino Acids in Hepatic Encephalopathy

Role of Branched Chain Amino Acids in Hepatic Encephalopathy

Lactulose, rifaximin or branched chain amino acids for hepatic encephalopathy: what is the evidence?

Hepatic encephalopathy (HE) is a serious complication of acute and chronic liver disease associated with severe morbidity and mortality. We performed updated random effects meta-analyses to evaluate the evidence for non-absorbable disaccharides (lactulose and lactitol), rifaximin and branched chain amino acids (BCAA). A meta-analysis of randomized trials showed that, compared with placebo or no intervention, non-absorbable disaccharides have beneficial effects on HE manifestations and prevention of HE episodes. The addition of rifaximin to non-absorbable disaccharides versus rifaximin alone was more beneficial than non-absorbable disaccharides used alone on both outcome measures. Likewise, a meta-analysis of randomised controlled trials found that oral BCAA supplements have beneficial effects on manifestations of HE compared with control supplements. The effect was found in a variety of clinical settings. No convincing effects of intravenous BCAA for episodic HE were identified. In conclusion, evidence-based treatment recommendations for patients with HE should include non-absorbable disaccharides combined with rifaximin or BCAA. Additional evidence is needed to evaluate the effect of combining all three interventions.

Branched-chain amino acids for hepatic encephalopathy.

Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA for patients with hepatic encephalopathy. We identified trials through The Cochrane Hepato-Biliary Group Controlled Trials Register (September 2002), (Issue 3, 2002), MEDLINE (1966-2002/09) and EMBASE (1980-2002/05), manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies. Randomised trials comparing BCAA with any kind of control therapy for hepatic encephalopathy were included, regardless of blinding, language, or publication status. Trial inclusion and data extraction were made independently by two reviewers. Our primary outcome was improvement of hepatic encephalopathy. Statistical heterogeneity was tested using random effects and fixed effect models. Binary outcomes are reported as risk ratios (RR) based on a random effects model. Eleven randomised trials (556 patients) assessing BCAA versus carbohydrates, neomycin/lactulose, or isonitrogenous control were included. The median number of patients in each trial was 55 (range 22 to 75). Follow-up after treatment was reported in four trials (median 17 days (range 6 to 30 days)). Compared to the control regimens, BCAA significantly increased the number of patients improving from hepatic encephalopathy at the end of treatment (risk ratio (RR) 1.31, 95% confidence interval (CI) 1.04 to 1.66, nine trials). We found no evidence of an effect of BCAA on survival (RR 1.06, 95% CI 0.98 to 1.14, eight trials) or adverse events (RR 0.97, 95% CI 0.41 to 2.31, three trials). Sensitivity analyses indicated that methodological quality had significant impact on the results. We found no evidence of an effect of BCAA on improvement of hepatic encephalopathy in trials with adequate generation of the allocation sequence (RR 1.01, 95% CI 0.84 to 1.23, three trials), adequate allocation concealment (RR 1.09, 95% CI 0.89 to 1.33, five trials), or adequate double-blinding (RR 1.20, 95% CI 0.83 to 1.73, three trials). We did not find convincing evidence that BCAA had a significant beneficial effect on patients with hepatic encephalopathy. The trials performed in this field were small with short follow-up and most had low methodological quality.

A systematic review on branched-chain amino acids for hepatic encephalopathy

A systematic review on branched-chain amino acids for hepatic encephalopathy

A systematic review on branched-chain amino acids for hepatic encephalopathy

A systematic review on branched-chain amino acids for hepatic encephalopathy

A systematic review on branched-chain amino acids for hepatic encephalopathy

A systematic review on branched-chain amino acids for hepatic encephalopathy

Neuroactive amino acids in hepatic encephalopathy.

There is abundant evidence to suggest that alterations of excitatory and inhibitory amino acids play a significant role in the pathogenesis of hepatic encephalopathy (HE) in both acute and chronic liver diseases. Brain glutamate concentrations are reduced in patients who died in hepatic coma as well as in experimental HE, astrocytic reuptake of glutamate is compromised in liver failure and postsynaptic glutamate receptors (both NMDA and non-NMDA subclasses) are concomitantly reduced in density. Recent studies in experimental acute liver failure suggest reduced capacity of the astrocytic glutamate transporter in this condition. Together, this data suggests that neuron-astrocytic trafficking of glutamate is impared in HE. Other significant alterations of neuroactive amino acids in HE include a loss of taurine from brain cells to extracellular space, a phenomenon which could relate both to HE and to brain edema in acute liver failure. Increased concentrations of benzodiazepine-like compounds have been reported in human and experimental HE. Clinical trials with the benzodiazepine antagonist flumazenil reveal a beneficial effect in some patients with HE; the mechanism responsible for this effect, however, remains to be determined.

Branched-chain amino acids for hepatic encephalopathy?

HepatologyVolume 13, Issue 4 p. 812-813 CorrespondenceFree Access Branched-chain amino acids for hepatic encephalopathy? Christian Gluud M.D., Dr. Med. Sci., Christian Gluud M.D., Dr. Med. Sci. Department of Hepatology, Hvidovre Hospital, University of Copenhagen, 2650-Hvidovre, DenmarkSearch for more papers by this authorHarold O. Conn M.D., Harold O. Conn M.D. Yale University School of Medicine Department of Internal Medicine 333 Cedar Street New Haven, Connecticut 06510–8056Search for more papers by this authorL. S. Eriksson M.D., L. S. Eriksson M.D. Department of Gastroenterology Huddinge University Hospital S141 86 Huddinge Stockholm, SwedenSearch for more papers by this author Christian Gluud M.D., Dr. Med. Sci., Christian Gluud M.D., Dr. Med. Sci. Department of Hepatology, Hvidovre Hospital, University of Copenhagen, 2650-Hvidovre, DenmarkSearch for more papers by this authorHarold O. Conn M.D., Harold O. Conn M.D. Yale University School of Medicine Department of Internal Medicine 333 Cedar Street New Haven, Connecticut 06510–8056Search for more papers by this authorL. S. Eriksson M.D., L. S. Eriksson M.D. Department of Gastroenterology Huddinge University Hospital S141 86 Huddinge Stockholm, SwedenSearch for more papers by this author First published: April 1991 https://doi.org/10.1002/hep.1840130438Citations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume13, Issue4April 1991Pages 812-813 ReferencesRelatedInformation

Branched-chain amino acids for hepatic encephalopathy?

Branched-chain amino acids for hepatic encephalopathy?

Branched-Chain Amino Acids in Hepatic Encephalopathy: Continuing Controversy

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Parenteral nutrition with branched-chain amino acids in hepatic encephalopathy: Meta analysis

Parenteral nutrition with branched-chain amino acids in hepatic encephalopathy: Meta analysis

Overestimation of serum concentrations of gamma-aminobutyric acid in patients with hepatic encephalopathy by the gamma-aminobutyric acid-radioreceptor assay.

Sera of patients with hepatic encephalopathy strongly inhibit the specific binding of gamma-aminobutyric acid to synaptic membranes. In a previous study, this inhibition of specific gamma-aminobutyric acid binding was attributed to gamma-aminobutyric acid itself, and it was assumed that serum gamma-aminobutyric acid is increased 5- to 30-fold in patients with hepatic encephalopathy. The findings of that study, however, were not confirmed by other analytical methods. Therefore, the validity of the gamma-aminobutyric acid-radioreceptor assay was tested. In view of the increased serum concentrations of several amino acids in hepatic encephalopathy, the effects of L-alpha-amino acids on the assay were studied. Five amino acids inhibited specific gamma-aminobutyric acid binding at a concentration of 0.5 mM or lower: glutamine; glutamate; taurine; proline, and OH-proline. Equimolar amounts of aminooxyacetate prevented the inhibition of specific gamma-aminobutyric acid binding by glutamine and glutamate but had no effect on that of gamma-aminobutyric acid, taurine, proline and OH-proline. Aminooxyacetate had no effect on specific gamma-aminobutyric acid binding itself. The inhibitory activity of a serum sample from a patient with hepatic encephalopathy was inhibited by 0.5 mM aminooxyacetate. The gamma-aminobutyric acid binding inhibitory activity of a serum sample of a patient with hepatic encephalopathy was purified by gel chromatography and contained several amino acids at concentrations of about 0.1 mM, 3.5 mM glutamine but no detectable gamma-aminobutyric acid. Accordingly, the gamma-aminobutyric acid binding inhibitory activity is not mediated by gamma-aminobutyric acid alone and is most likely due to glutamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Branched chain amino acids in hepatic encephalopathy

Seventy-five patients with acute hepatic decompensation superimposed on chronic alcoholic cirrhosis were prospectively randomized for a blinded trial of the treatment of hepatic.

Contribution of the arterial blood ketone body ratio to elevate plasma amino acids in hepatic encephalopathy of surgical patients

To clarify the role of hepatic metabolic derangements in elevated plasma amino acid levels, the patterns of plasma amino acids in 17 surgical patients with hepatic failure were analyzed in relation to the blood ketone body ratio (acetoacetate to β-hydroxybutyrate), which reflects the mitochondrial redox potential. The blood ketone body ratios were 0.49 in eight alert patients with hepatic failure and 0.28 in nine patients with grade IV hepatic coma, compared with values of 0.79 to 6.42 in patients with healthy livers. The plasma concentrations of alanine, proline, phenylalanine, and tyrosine were negatively correlated with the blood ketone body ratio. Elevations of alanine, phenylalanine, tyrosine, and glutamate were greater in comatose patients than in alert patients. Also, the molar ratios between the plasma concentrations of the branched-chain amino acid and the aromatic amino acids were positively correlated with the blood ketone body ratio (r = 0.78, p < 0.0001). We suggest that a reduced mitochondrial redox potential, coupled with enhanced muscle breakdown, results in inhibition in the entrance of the amino acids into the Krebs' cycle and then the characteristic changes in the free amino acid patterns which result in hepatic coma.