Probiotics for patients with compensated liver cirrhosis: a double-blind placebo-controlled study. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy. A randomised double-blind placebo-controlled trial with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 for maintenance of remission in ulcerative colitis. Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Neomycin-sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy. A controlled, double-blind clinical trial. Efficacy of Lactobacillus GG in aboriginal children with acute diarrhoeal disease: a randomised clinical trial. Enterococcus lactic acid bacteria strain SF68 and lactulose in hepatic encephalopathy: a controlled study.
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. Minimal hepatic encephalopathy (MHE), the preclinical stage of overt hepatic encephalopathy (OHE), is a significant condition affecting up to 60% of cirrhotics. All MHE therapies modify gut microflora, but consensus regarding MHE treatment and long-term adherence studies is lacking. The aim was to determine the effect of probiotic supplementation in the form of a food item, probiotic yogurt, on MHE reversal and adherence.
                Nonalcoholic MHE cirrhotics (defined by a standard psychometric battery) were randomized with unblinded allocation to receive probiotic yogurt (with proven culture stability) or no treatment (no Rx) for 60 days in a 2:1 ratio. Quality of life (short form [SF]-36), adherence, venous ammonia, model of end-stage liver disease (MELD) scores, and inflammatory markers (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6) were also measured. Outcomes were MHE reversal using blinded scoring, OHE development, and adherence.
                Twenty-five patients (17 yogurt, 8 no Rx; 84% Child class A) were enrolled. A significantly higher percentage of yogurt patients reversed MHE compared to no Rx patients (71%vs 0%, P= 0.003, intention-to-treat). Yogurt patients demonstrated a significant improvement in number connection test-A (NCT-A), block design test (BDT), and digit symbol test (DST) compared to baseline/no Rx group. Twenty-five percent of no Rx versus 0% of yogurt patients developed OHE during the trial. Eighty-eight percent of yogurt patients were adherent. No adverse effects or change in covariates were observed. All patients who completed the yogurt arm were agreeable to continue yogurt for 6 months if needed.
                This trial demonstrated a significant rate of MHE reversal and excellent adherence in cirrhotics after probiotic yogurt supplementation with potential for long-term adherence. Minimal hepatic encephalopathy (MHE) is associated with poor quality of life and increased work disability. Treatment with lactulose and probiotics has shown some benefit. We compared lactulose with probiotics and a combination of lactulose plus probiotics in the treatment of MHE.
                One hundred and ninety cirrhotic patients without overt encephalopathy [Child's A grade 71 patients (37.4%), Child's B grade 72 patients (37.9%), Child's C grade 47 patients (24.7%)] were evaluated by psychometry (number connection tests A and B or figure connection tests A and B) and P300 auditory event-related potential (P300ERP). MHE was diagnosed by abnormal psychometry and/or P300ERP. Patients were randomized to receive lactulose [group A (n=35): dose 30-60 ml/day], probiotics [group B (n=35): dose 1 capsule three times/day, each capsule contained Streptococcus faecalis 60 million, Clostridium butyricum 4 million, Bacillus mesentricus 2 million, lactic acid bacillus 100 million] and lactulose plus probiotics [group C (n=35)] for 1 month. Response was defined by normalization of the abnormal test parameters.
                MHE was diagnosed in 105 (55.2%) patients. Of the 105 patients, 75 (71%) had both abnormal psychometry and P300ERP, whereas 90 (86%) had abnormal psychometry alone, and 89 patients (85%) had abnormal P300ERP alone. Significant improvement was seen in abnormal psychometry tests (group A: n=31 vs. n=12, group B: n=29 vs. n=14, group C: n=30 vs. n=10), P300ERP (group A: 376.8+/-22.3 vs. 344.3+/-30.6 ms, group B: 385.4+/-28.5 vs. 355.5+/-27.9 ms, group C: 387.7+/-27.5 vs. 347.7+/-31.5 ms) and venous ammonia levels (group A: 102.3+/-63.1 vs. 69.3+/-33.3 micromol/l, group B: 108.2+/-37.5 vs. 75.7+/-33.0 micromol/l, group C: 96.3+/-27.7 vs. 68.7+/-28.4 micromol/l) in lactulose, probiotics and a combination of lactulose plus probiotics groups after treatment. Normalization of abnormal psychometry and P300ERP was seen in 54.8, 51.6 and 56.6% of patients treated with lactulose, probiotics and lactulose plus probiotics groups, respectively.
                A total of 55% of the patients with cirrhosis had MHE. Lactulose or probiotics or combinations of both are equally effective in the treatment of MHE. To investigate the clinical effect of treatment with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 (Probio-Tec AB-25) to maintain remission in patients with ulcerative colitis.
                Patients with left-sided ulcerative colitis in remission - including proctitis and at least one relapse within the last year were randomised (2:1) in a double-blind placebo-controlled study to Probio-Tec AB-25 or placebo for 52 weeks. The patients were evaluated clinically, endoscopically and histologically at entry and if relapsing. No other medication for ulcerative colitis than the study drug was allowed during the study. Primary endpoint was maintenance of clinical remission, secondary endpoints comparisons of days to relapse, and safety and tolerability of the study drug. The concentrations of the probiotic bacterial strains in stool were analysed in a subset of patients.
                Thirty-two patients were randomised. Twenty patients received Probio-Tec AB-25 and twelve patients received placebo. Five patients (25%) in the Probio-Tec AB-25 group and one patient (8%) in the placebo group maintained remission after 1 year of treatment (p=0.37). The median time to relapse was 125.5days (range 11-391 days) in the probiotic group and 104 days (range 28-369 days) in the placebo group respectively, (p=0.683). Probio-Tec AB-25 was overall well tolerated.
                In this small randomised placebo-controlled trial no significant clinical benefit of Probio-Tec AB-25 could be demonstrated in comparison with placebo for maintaining remission in patients with left-sided ulcerative colitis. A difference may be achieved in larger studies, but the clinical significance of this would be questionable. This study was registered in ClinicalTrial.gov (NCT00268164).
                Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence.
                In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285 +Lactobacillus casei LBC80R Bio-K+ CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days.
                Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1.
                The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308). 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. In a double-blind, randomized study the efficacy of lactulose was compared with neomycin-sorbitol in 45 episodes of acute nitrogenous portal-systemic encephalopathy (PSE) induced by dietary protein, azotemia, or gastrointestinal hemorrhage. All patients had underlying cirrhosis, and at the time of randomization had encephalopathy of at least grade 2 severity and arterial ammonia concentrations greater than 150 microgram/100 ml. Two thirds of the patients in each group returned to normal mental status and more than 80% in each group showed at least one grade improvement in mental state. In addition, there was equivalent improvement in asterixis, in the performance of the Number Connection Test, in the electroencephalographic pattern, and in arterial ammonia concentration. The principal difference between the two groups was a greater reduction in stool pH after lactulose therapy than after neomycin-sorbitol therapy. One patient randomized to neomycin-sorbitol had to be withdrawn from the study because of persistent vomiting related to the administration of the medication. Otherwise there were no complications attributable to therapy in either group. These data suggest that neomycin-sorbitol and lactulose are equally effective in the treatment of acute nitrogenous portal-systemic encephalopathy. The effectiveness of probiotic therapy for acute rotavirus infectious diarrhoea in an indigenous setting with bacterial/parasitic diarrhoea is unclear. In the present study, we assessed the efficacy of probiotics in Australian Aboriginal children in the Northern Territory admitted to hospital with diarrhoeal disease.
                A randomised double-blind placebo-controlled study was conducted in Aboriginal children (ages 4 months-2 years), admitted to hospital with acute diarrhoeal disease (>3 loose stools per day). Children received either oral Lactobacillus GG (5 x 10(9) colony-forming units 3 times per day for 3 days; n = 33) or placebo (n = 31). Small intestinal functional capacity was assessed by the noninvasive 13C-sucrose breath test on days 1 and 4.
                Both groups showed mean improvement in the sucrose breath test after 4 days; however, there was no difference (mean, 95% confidence interval) between probiotic (2.9 [cumulative percentage of dose recovered at 90 minutes]; 1.7-4.2) and placebo (3.7; 2.3-5.2) groups. Probiotics did not change the duration of diarrhoea, total diarrhoea stools, or diarrhoea score compared with placebo. There was a significant (P < 0.05) difference in diarrhoea frequency on day 2 between probiotics (3.3 [loose stools]; 2.5-4.3) and placebo (4.7; 3.8-5.7) groups.
                Lactobacillus GG did not appear to enhance short-term recovery following acute diarrhoeal illness in this setting. Forty cirrhotic patients with non-advanced hepatic encephalopathy were randomly allocated into groups which were given orally either two capsules three times daily of a preparation of Enterococcus lactic acid bacteria strain SF68 or 30 ml lactulose four times daily. The patients were evaluated over a 10-day course of treatment and for 10 days post-treatment. The Enterococcus SF68 preparation proved to be as effective as lactulose in lowering blood ammonia, and in improving mental state and psychometric performance. Moreover, the effects of Enterococcus SF68, contrary to that of lactulose, persisted longer after treatment withdrawal. Some patients reported diarrhoea and abdominal pain with lactulose. Lactulose is a standard therapy in the treatment of patients with hepatic encephalopathy. In this study, however, the use of the Enterococcus SF68 preparation was shown to offer advantages over lactulose in these patients.
The trials we located suffered from a high risk of systematic errors ('bias') and high risk of random errors ('play of chance'). While probiotics appear to reduce plasma ammonia concentration when compared with placebo or no intervention, we are unable to conclude that probiotics are efficacious in altering clinically relevant outcomes. Demonstration of unequivocal efficacy is needed before probiotics can be endorsed as effective therapy for hepatic encephalopathy. Further randomised clinical trials are needed.