Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1–2 hepatic encephalopathy

Loguercio, C.; Abbiati, R.; Rinaldi, Mario; Romano, Adriana; Blanco, C. Del Vecchio; Coltortí, M

doi:10.1016/0168-8278(95)80309-2

Cited by 105 publications

(55 citation statements)

References 18 publications

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“…The use of probiotics was proposed as a potential alternative treatment for HE, based on previous experimental and clinical studies. 21,22,[33][34][35] In this study, we showed that oral and rectal administration of L. plantarum, a species used in probiotic formulations, decreased both blood and fecal ammonia levels in rodent models of HA. In addition, we showed for the first time that this probiotic increased survival in a murine model of fulminant hepatic failure when compared to lactulose treatment.…”

Section: Discussionmentioning

confidence: 95%

Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents

et al. 2008

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Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia. In this study, we aimed to modulate hyperammonemia in three rodent models by administration of wild-type Lactobacillus plantarum, a genetically engineered ammonia hyperconsuming strain, and a strain deficient for the ammonia transporter. Wild-type and metabolically engineered L. plantarum strains were administered in ornithine transcarbamoylase-deficient Sparse-fur mice, a model of constitutive hyperammonemia, in a carbon tetrachloride rat model of chronic liver insufficiency and in a thioacetamide-induced acute liver failure mice model. Constitutive hyperammonemia in Sparse-fur mice and hyperammonemia in a rat model of chronic hepatic insufficiency were efficiently decreased by Lactobacillus administration. In a murine thioacetamide-induced model of acute liver failure, administration of probiotics significantly increased survival and decreased blood and fecal ammonia. The ammonia hyperconsuming strain exhibited a beneficial effect at a lower dose than its wild-type counterpart. Improved survival in the acute liver failure mice model was associated with lower blood ammonia levels but also with a decrease of astrocyte swelling in the brain cortex. Modulation of ammonia was abolished after administration of the strain deficient in the ammonium transporter. Intestinal pH was clearly lowered for all strains and no changes in gut flora were observed. Conclusion: Hyperammonemia in constitutive model or after acute or chronic induced liver failure can be controlled by the administration of L. plantarum with a significant effect on survival. The mechanism involved in this ammonia decrease implicates direct ammonia consumption in the gut. (HEPATOLOGY 2008;48:1184-1192 H yperammonemia (HA) is a well-known complication of acute and chronic liver diseases and plays a central role in the pathogenesis of hepatic encephalopathy (HE). [1][2][3][4][5] This neurological dysfunction results, at least in part, from an increase in plasma ammonia level and the severity of the symptoms correlates with blood ammonia level. 6-9 Animal models used in studying hyperammonemic disorders are multiple: fulminant hepatic failure, 10 chronic liver failure, 11 or urea cycle deficiency. 12 Ammonia is produced by many tissues but its major external source results from deaminase and urease activities of the gut flora. Although its absorption occurs through the intestinal epithelium, ammonia is carried by the portal vein into the liver where it is metabolized into urea. 13 Classical treatments of HE, except through liver transplantation and liver replacement therapies, consist in decreasing the ammonia production of urease-positive bacteria by antibiotics or decreasing the ammonia absorption into the gut by acidifying the colon content with nonabsorbable sugars such as lactulose. 4,[13][14][1...

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Section: Discussionmentioning

confidence: 95%

Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents

et al. 2008

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“…Notably, patients who responded to treatment with Enterococcus faecium SF68 maintained clinical improvement during a 2-week period off-treatment, whereas encephalopathy status typically returned to baseline during drug-free periods in lactulose-treated patients. 37 Future studies of the effect of synbiotics and fermentable fiber alone on HE, using a more extensive battery of neuropsychological tests than we employed in this current report, should similarly assess the durability of clinical response following treatment withdrawal, along with the effects of longer durations of treatment.…”

Section: Discussionmentioning

confidence: 99%

Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis

Liu¹,

Duan²,

Ha³

et al. 2004

Hepatology

563

429

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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.

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“…Loguercio et al 36,37 showed that long-term administration of Enterococcus faecium (SF68) is at least as useful as lactulose for the chronic treatment of chronic HE. In a meta-analysis by McGee et al 38 …”

Section: Probioticsmentioning

confidence: 99%

Management of Overt Hepatic Encephalopathy

Sharma

2015

Journal of Clinical and Experimental Hepatology

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Hepatic encephalopathy (HE) is an important complication of cirrhosis with significant morbidity and mortality. Management of HE primarily involves avoidance of precipitating factors and administration of various ammonia-lowering therapies such as non-absorbable disaccharides, antimicrobial agents like rifaximin and L-ornithine L-aspartate. The non-absorbable disaccharides which include lactulose and lactitol are considered the first-line therapy for the treatment of HE and in primary and secondary prophylaxis of HE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects. Rifaximin is effective in treatment of HE and recent systemic reviews found it comparable to disaccharides and is effective in secondary prophylaxis of HE. H epatic encephalopathy (HE) is a complex neuropsychiatric syndrome, which may complicate acute, chronic liver failure or patients with portal-systemic shunting. It is characterized by changes in mental state including a wide range of neuropsychiatric symptoms ranging from minor signs of altered brain function to deep coma. 1,2 It is one of the commonest indications for admission in intensive care unit in patients with advanced cirrhosis. There were over 40 000 patients hospitalized in the United States alone for a primary diagnosis of HE, resulting in total charges of approximately $932 million. Data in other countries are lacking, hence it causes a huge burden financially to the patient and society. 3 The West Haven Criteria are most often used to grade HE, with scores ranging from I-IV (IV being coma). However, it is a challenge to diagnose patients with minimal hepatic encephalopathy (MHE) or grade 1 HE; so it might be practical to combine these entities and name them covert HE for clinical use and overt HE to patients with grade II to IV. 1,4,5 One of the major tenets of the pathophysiology of HE is hyperammonemia that results from an increased nitrogenous load from the gastrointestinal tract and reduced urea synthesis both due to portal-systemic shunting and decreased urea hepatic synthesis. Brain and skeletal muscle neither remove nor produce ammonium in normal conditions, but they are able to seize ammonium during hyperammonemia, releasing glutamine. Ammonia is produced both by bacterial degradation of amines, aminoacids, purines, and urea as well as enterocytic glutaminase activity that converts glutamine to glutamate and ammonia. 6,7 Astrocytes play an important role in the pathogenesis of HE with consequences for neuronal function. Astrocytes have the ability to eliminate ammonia by the synthesis of glutamine through amidation of glutamate by the enzyme glutamine synthetase Hyperammonemia leads to the accumulation of glutamine within astrocytes, which exerts an osmotic stress that causes astrocytes to take in water and swell. 8,9 This article reviewed the clinical impact, pathogenesis, and management of overt HE in patients with cirrhosis. Articles published between January 1960 and November 2013 were acquired through a MEDLINE search of different combi...

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Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1–2 hepatic encephalopathy

Cited by 105 publications

References 18 publications

Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents

Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents

Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis

Management of Overt Hepatic Encephalopathy

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