Disease-specific amino acid infusion (F080) in hepatic encephalopathy: a prospective, randomized, double-blind, controlled trial. Use of branched chain amino acids for treating hepatic encephalopathy: clinical experiences. Comparison between neomycin and lactulose in 173 patients with hepatic encephalopathy: a randomized clinical study. Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy. A double-blind study of 65 patients with cirrhosis. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy. Acidifying enemas (lactitol and lactose) vs. nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: a double-blind, randomized clinical trial. Probiotics for patients with compensated liver cirrhosis: a double-blind placebo-controlled study. [Non-insulin-dependent diabetes mellitus associated with nonalcoholic liver cirrhosis: an evaluation of treatment with the intestinal alpha-glucosidase inhibitor acarbose].
Seventy-five patients with acute hepatic decompensation superimposed on chronic alcoholic cirrhosis were prospectively randomized for a blinded trial of the treatment of hepatic encephalopathy. The control group received 4 g of enteral neomycin daily along with 25% dextrose by a central venous catheter. The experimental group received a placebo resembling neomycin and isocaloric dextrose plus a modified amino acid mixture enriched with branched-chain amino acids to 36% and deficient in aromatic amino acids and methionine. Thirty patients in the F080 group and 29 in the control group completed the trial. The group receiving the modified amino acid mixture demonstrated a statistically significant improvement in encephalopathy as compared to the neomycin group, while maintaining nitrogen equilibrium. Survival and discharge from the hospital were statistically greater in the group treated with the modified amino acid solution and hypertonic dextrose. Treatment of hepatic encephalopathy in the presence of hepatic decompensation with an amino acid solution formulated for its treatment seems to produce faster, more complete recovery with improved capacity for nutritional support. The efficacy of branched chain amino acids in two consecutive clinical studies in patients with severe hepatic encephalopathy was tested. In the preliminary uncontrolled study 19 patients with grade 3-4 hepatic encephalopathy were given an intravenous solution containing leucine 11 g/l, isoleucine 9 g/l, and valine 8.4 g/l in 20% dextrose. A complete recovery of mental state was obtained in all patients in a mean time of 20.5 hours. In a subsequent controlled study 40 patients with grade 3-4 hepatic encephalopathy were randomly assigned to receive intravenous branched chain amino acid in 20% dextrose (group A) or oral lactulose (group B). Twelve patients (70.6%) in group A and eight (47%) in group B regained consciousness in a mean time of 27.6 and 31.5 hours, respectively. The difference in the recovery rate between the two groups, although evident, was not significant. Intravenous branched chain amino acids are thus at least as effective as lactulose in reversing hepatic coma. These data argue strongly in favour of a therapeutic effect of branched chain amino acids in the treatment of hepatic encephalopathy in patients with chronic liver failure. A randomized study was performed in order to compare the course of hepatic encephalopathy in patients treated with neomycin plus magnesium sulfate or with lactulose. Admission criteria were: morphological diagnosis of cirrhosis and absence of comorbidity, of contraindications to drugs, or of previous treatments which could influence the outcome. The treatment groups were similar in terms of clinical characteristics, fatalities, recovery rate from grade 1 encephalopathy, and disappearance rate of neuropsychiatric signs. Transitions from severe to grade 1 or 0 encephalopathy showed a 0.17 (NS) difference in favor of neomycin. Early therapy and evidence of precipitating factors showed a favorable prognostic significance. Ascites, hyperbilirubinemia, poor nutritional state, and hypoprothrombinemia showed bad prognostic significance. This is the first large-scale investigation on hepatic encephalopathy. It demonstrated a similar effectiveness of the two drugs in grade 1 encephalopathy and provides a basis for drug selection in the current management of the syndrome. We studied the effects of infusion of a branched chain enriched amino acid mixture versus glucose on acute hepatic encephalopathy in patients with cirrhosis. Sixty-five patients were randomly treated with 1 g/kg per day of an amino acid mixture with 40% branched chain contents (32 patients), or isocaloric glucose (33 patients) for a maximum of 16 days. The regimens further included glucose infusion to a total of 26.5 kcal/kg per day and lactulose. The patients took part in the study for 5-6 days. In each group 17 patients woke up. In the amino acid group eleven died and four developed renal failure. In the glucose group ten died, three developed renal and two respiratory failure, and one remained encephalopathic. The coma score worsened in three of the patients who died in the amino acid group, but in all patients who died in the glucose group. The negative nitrogen balance on entry reversed in the amino acid group, but not in the glucose group. Thus, the branched chain enriched amino acid supplement did not change the prognosis for wake-up, but had other effects on the cerebral state and on nitrogen homeostasis. Minimal hepatic encephalopathy (MHE) is an important disorder that may seriously impair daily functioning and quality of life in patients with cirrhosis. Treatment with lactulose is of benefit. The possible role of synbiotics (probiotics and fermentable fiber) has not been assessed. We screened 97 consecutive cirrhotic patients without overt hepatic encephalopathy for MHE using the number connection test and measurement of brainstem auditory evoked potentials. MHE, defined by abnormality on at least one test modality, was present in 58 (60%) patients. Fifty-five of these patients with MHE were randomized to receive a synbiotic preparation (n = 20), fermentable fiber alone (n = 20), or placebo (n = 15) for 30 days. Cirrhotic patients with MHE were found to have substantial derangements in the gut microecology, with significant fecal overgrowth of potentially pathogenic Escherichia coli and Staphylococcal species. Synbiotic treatment significantly increased the fecal content of non-urease-producing Lactobacillus species at the expense of these other bacterial species. Such modulation of the gut flora was associated with a significant reduction in blood ammonia levels and reversal of MHE in 50% of patients. Synbiotic treatment was also associated with a significant reduction in endotoxemia. The Child-Turcotte-Pugh functional class improved in nearly 50% of cases. Treatment with fermentable fiber alone was also of benefit in a substantial proportion of patients. In conclusion, treatment with synbiotics or fermentable fiber is an alternative to lactulose for the management of MHE in patients with cirrhosis. Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome in patients with liver disease. It was suggested that Bifidobacterium+fructo-oligosaccharides (FOS) may decrease blood and brain ammonia levels.
                The study was conducted to compare the efficacy of Bifidobacterium+FOS and lactulose in patients with HE.
                One hundred and twenty-five patients (35 hepatitis B virus infected, 70 hepatitis C virus infected and 20 cryptogenetic cirrhosis) were enrolled in the study. Patients were randomized either to a treatment for 60 days with Bifidobacterium and FOS (group A) or into-group receiving lactulose (group B) in double-blind.
                After 30 days of the study period, the Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of Trail Making Test B (TMT B) (P<0.005), and a significant increase of Symbol Digit Modalities Test (P<0.001) and Block Design Test (P<0.001).After 60 days of the study period, the Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of NH4 fasting HE1 (P<0.001), TMT A (P<0.05), TMT B (P<0.001), and a significant increase of Symbol Digit Modalities Test (P<0.001) and Block Design Test (P<0.001).
                The treatment with Bifidobacterium+FOS is an alternative to the use of lactulose in patients with cirrhosis, for its usefulness in reducing blood ammonia levels and improvement of psychometric tests. A double-blind, controlled trial to study the efficacy of acidifying enemas of lactitol, a new galactoside-sorbitol disaccharide, and lactose vs. nonacidifying tap-water enemas was performed in 45 episodes of acute portal-systemic encephalopathy. At the time of randomization, all patients had encephalopathy of at least Grade 2+ severity, delay in the performance of number connection tests and hyperammonemia. A sequential analysis was performed which revealed after the inclusion of the first 20 patients, a significant failure of the nonacidifying enemas as compared to the lactitol enemas (p less than 0.004). The tap-water enema group was, therefore, suspended but the rest of the study continued after rerandomization for lactose and lactitol groups. A favorable response to treatment was obtained in 19 (86%) of the patients receiving lactitol enemas and in 14 (78%) of those receiving lactose enemas. A similar significant improvement in portal-systemic encephalopathy parameters and index was observed after both treatments. Both types of acidifying enemas induced a significant pH decrease in stool (p less than 0.05). These data suggest that acidifying agents like lactose and lactitol are effective and superior to tap-water enemas for the treatment of acute nitrogenous portal-systemic encephalopathy. Gut flora is related to the major complications of liver cirrhosis including hepatic encephalopathy, spontaneous bacterial peritonitis, and variceal bleeding. Prior studies have reported a beneficial effect of gut flora modification with probiotic bacteria in patients with minimal hepatic encephalopathy. We aimed to study the effect of probiotics on clinical and laboratory parameters of patients with compensated cirrhosis.
                A double-blind placebo-controlled study that included patients with liver cirrhosis and at least one major complication of cirrhosis in the past, clinical evidence of portal hypertension, or decreased hepatic synthetic function. Participants were randomly assigned to receive probiotic capsules containing Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium lactis, and Streptococcus thermophiles or placebo for a period of 6 mo.
                A total of 36 patients were available for final analysis (distributed equally between the probiotic and placebo groups). The administration of probiotics was not associated with significant differences in either clinical or laboratory parameters between the two groups. Because the lack of a beneficial effect may be related to the compensated liver disease of patients, we conducted a subanalysis of patients with baseline ammonia levels > 50 mmol/L. In this subgroup, the administration of probiotics appeared to significantly reduce the ammonia levels starting after 1 mo of treatment. However, this effect diminished and lost its significance following comparison to the placebo group.
                Our study did not show a significant beneficial effect of probiotic supplementation in patients with compensated liver cirrhosis. Nevertheless, it points toward a possible positive effect of probiotics in patients with above normal baseline ammonia levels. This issue requires further investigation in larger cohorts.
                Copyright Â© 2011 Elsevier Inc. All rights reserved. Non-insulin-dependent diabetes mellitus not responding to diet only in patients with non-alcoholic liver cirrhosis is characterized by high post-prandial hyperglycemia. The aim of this study was to evaluate the safety and efficacy of 24 weeks of treatment with 300 mg acarbose per day in 76 consecutive outpatients affected by type 2 diabetes and well-compensated liver cirrhosis. The study design was double-blind cross-over vs placebo. All patients tolerated both treatments well, and no significant variations in liver function tests were observed (< 5% vs pre-treatment). A significant reduction of several parameters was observed only after acarbose: fasting glycemia (19 +/- 6 vs 2 +/- 0.5%; p < 0.01), post-prandial glycemia (41 +/- 9 vs 3 +/- 0.6%; p < 0.01), mean glycemia (30 +/- 8 vs 14 +/- 5%; p < 0.01), daily glycemic variation (52 +/- 8 vs 8 +/- 1%; p < 0.01), HbA1c (16 +/- 1 vs 2 +/- 0.5; p < 0.05), incremental area of C-peptide after a standard meal (80 +/- 19 vs 200 +/- 36 ng/mL/300 min; p < 0.01). After acarbose a significant increase of intestinal voiding/week (98 vs 28%; p < 0.01) and a parallel reduction of blood ammonia levels (52 +/- 9 vs 9 +/- 5%; p < 0.01) were observed. Results clearly document the good tolerability and the absence of toxic effects of acarbose on the liver, due to a theoretic absence of both absorption by the gut and hepatic metabolism of the drug. In fact, acarbose increases peristaltic movement of the gut, stimulates the proliferation of saccharolytic bacteria and simultaneously reduces proteolytic bacterial proliferation, thus actively reducing blood ammonia levels. These unexpected effects of acarbose may be used to advantage for the treatment of type 2 diabetes mellitus in patients with well-compensated liver cirrhosis.
This systematic review questions the beneficial effects of nonabsorbable disaccharides and highlights that there is insufficient high-quality evidence to support this treatment. We found that antibiotics appeared to be superior to nonabsorbable disaccharides in improving hepatic encephalopathy, but it is unclear whether this difference in treatment effect is clinically important to patients. Nonabsorbable disaccharides should not serve as comparator in randomised trials on hepatic encephalopathy.