Treatment of Chronic Portal-Systemic Encephalopathy With Lactulose

Müller, Jean-Baptiste; Guggenheim, Paul; Haemmerli, Urs Peter

doi:10.1016/s0140-6736(66)91573-x

Cited by 76 publications

(19 citation statements)

References 7 publications

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“…Lactulose can improve the life quality of people suffering from hepatic encephalopathy. This prebiotic also has preventive effects on hepatic encephalopathy [143,168,169,170]. Lactulose exerts its beneficial effects on hepatic encephalopathy through different pathways.…”

Section: Prebiotics Mechanisms For Health Maintenance and Protectimentioning

confidence: 99%

Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications

Davani-Davari

Negahdaripour

Karimzadeh

et al. 2019

Foods

1,023

536

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Prebiotics are a group of nutrients that are degraded by gut microbiota. Their relationship with human overall health has been an area of increasing interest in recent years. They can feed the intestinal microbiota, and their degradation products are short-chain fatty acids that are released into blood circulation, consequently, affecting not only the gastrointestinal tracts but also other distant organs. Fructo-oligosaccharides and galacto-oligosaccharides are the two important groups of prebiotics with beneficial effects on human health. Since low quantities of fructo-oligosaccharides and galacto-oligosaccharides naturally exist in foods, scientists are attempting to produce prebiotics on an industrial scale. Considering the health benefits of prebiotics and their safety, as well as their production and storage advantages compared to probiotics, they seem to be fascinating candidates for promoting human health condition as a replacement or in association with probiotics. This review discusses different aspects of prebiotics, including their crucial role in human well-being.

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Section: Prebiotics Mechanisms For Health Maintenance and Protectimentioning

confidence: 99%

Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications

Davani-Davari

Negahdaripour

Karimzadeh

et al. 2019

Foods

1,023

536

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“…Accordingly, direct elimination of ammonia from the gut via purgatory treatments and reduction of proteolytic bacterial flora, as well as reduction of inflammation secondary to gut translocation of bacterial by-products, form the mainstay of HE therapy. Nonabsorbable synthetic disaccharides, such as lactulose and lactitol, were first introduced in 1966 50 and constitute first-line therapy for HE. 1 Their mechanism of action is likely multifactorial.…”

Section: Article Highlightsmentioning

confidence: 99%

Refining the Ammonia Hypothesis

Tapper

Jiang

Patwardhan

2015

Mayo Clinic Proceedings

129

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Hepatic encephalopathy (HE) is one of the most important complications of cirrhosis and portal hypertension. Although the etiology is incompletely understood, it has been linked to ammonia directly and indirectly. Our goal is to review for the clinician the mechanisms behind hyperammonemia and the pathogenesis of HE to explain the rationale for its therapy. We reviewed articles collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic Reviews, and Google Scholar between October 1, 1948, and December 8, 2014, and by a manual search of citations within retrieved articles. Search terms included hepatic encephalopathy, ammonia hypothesis, brain and ammonia, liver failure and ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia, portosytemic shunt, ammonia and lactulose, rifaximin, zinc, and nutrition. Ammonia homeostatsis is a multiorgan process involving the liver, brain, kidneys, and muscle as well as the gastrointestinal tract. Indeed, hyperammonemia may be the first clue to poor functional reserves, malnutrition, and impending multiorgan dysfunction. Furthermore, the neuropathology of ammonia is critically linked to states of systemic inflammation and endotoxemia. Given the complex interplay among ammonia, inflammation, and other factors, ammonia levels have questionable utility in the staging of HE. The use of nonabsorbable disaccharides, antibiotics, and probiotics reduces gut ammoniagenesis and, in the case of antibiotics and probiotics, systemic inflammation. Nutritional support preserves urea cycle function and prevents wasting of skeletal muscle, a significant site of ammonia metabolism. Correction of hypokalemia, hypovolemia, and acidosis further assists in the reduction of ammonia production in the kidney. Finally, early and aggressive treatment of infection, avoidance of sedatives, and modification of portosystemic shunts are also helpful in reducing the neurocognitive effects of hyperammonemia. Refining the ammonia hypothesis to account for these other factors instructs a solid foundation for the effective treatment and prevention of hepatic encephalopathy.

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“…The result is acidification of colonic contents and variable diarrhea, depending upon lactulose dosage. In 1966 Bircher et al56 described the first use of lactulose to treat hepatic encephalopathy in CLD – the encephalopathy of two of three patients appeared to respond in an uncontrolled study. The stated rationale was the belief that a colonic acidic acid environment reduces the bacterial production of putative neuro toxins, one of which is ammonia.…”

Section: Mechanisms Of Action Of Lactulose and Rifaximinmentioning

confidence: 99%

<p>Use Of Quantitative Modelling To Elucidate The Roles Of The Liver, Gut, Kidney, And Muscle In Ammonia Homeostasis And How Lactulose And Rifaximin Alter This Homeostasis</p>

Levitt¹,

Levitt²

2019

IJGM

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Humans must eliminate approximately 1M of ammonia per day while maintaining the blood concentration of this potent neurotoxin at a concentration of only about 30 µM. The mechanisms producing such effective ammonia homeostasis are poorly understood by clinicians due to the multiple organs (liver, gut, kidney and muscle) involved in ammonia homeostasis. Based on literature values we present a novel, simplified description of normal and disordered ammonia and the potential mechanisms whereby the drugs used to treat hepatic encephalopathy, lactulose and rifaximin, lower the blood ammonia concentration. Concepts discussed include the following: 1) only about 44 mmol of ammonia/day (4.4% of total production) reaches the peripheral circulation due to the efficient linkage of amino deamination and the urea cycle in hepatic mitochondria; 2) the gut and kidney contribute roughly equally to delivery of this 44 mmol/day to systemic blood; 3) the bulk of gut ammonia production seemingly originates in the small bowel from bacterial deamination of urea by bacteria and mucosal deamination of circulating and ingested glutamine; 4) the apparent production of ammonia in the small bowel markedly exceeds that quantity that enters the portal blood, indicating that ammonia disposal mechanisms in the small bowel play a major role in ammonia homeostasis. With regard to the hyperammonemia of chronic liver disease: 1) shunting of portal blood around the liver, by itself, can account for commonly observed ammonia elevations; 2) severe portal hypertension causes an increased release of ammonia by the kidney; 3) high blood ammonia is associated with an unexplained massive increase in the muscle uptake of ammonia that could play an important role in limiting hyperammonemia; and 4) a major action of lactulose administration may be the enhancement of ammonia uptake by small bowel bacteria, while the mechanism of action of rifaximin is unclear.

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Treatment of Chronic Portal-Systemic Encephalopathy With Lactulose

Cited by 76 publications

References 7 publications

Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications

Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications

Refining the Ammonia Hypothesis

<p>Use Of Quantitative Modelling To Elucidate The Roles Of The Liver, Gut, Kidney, And Muscle In Ammonia Homeostasis And How Lactulose And Rifaximin Alter This Homeostasis</p>

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