Oral Branched-Chain Amino Acids Have a Beneficial Effect on Manifestations of Hepatic Encephalopathy in a Systematic Review with Meta-Analyses of Randomized Controlled Trials

Gluud, Lise Lotte; Dam, Gitte; Borre, Mette; Les, Íñigo; Córdoba, Juan; Marchesini, Giulio; Aagaard, Niels Kristian; Risum, Niels; Vilstrup, Hendrik

doi:10.3945/jn.113.174375

Cited by 100 publications

(81 citation statements)

References 35 publications

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“…The analysis revealed that BCAA supplementation had a beneficial effect on reducing HE manifestations. No difference was found regarding overall mortality, albumin, or nitrogen balance [81] . Both of these reviews examined BCAA in liver cirrhosis in general, but so far no reviews have specifically examined BCAA in older adults with cirrhosis.…”

Section: Branched Chain Amino Acid Supplementation In Older Adults Wimentioning

confidence: 72%

Protein Recommendations for Older Adults with Cirrhosis: A Review

Iiames

Logomarsino

2015

Journal of Gastroenterology and Hepatology Research

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Protein intake has a key role in liver cirrhosis in older adults. However, types and amounts of protein intake in cirrhosis have been controversial. The aim of this paper is to investigate the optimal protein intake for management of cirrhosis and prevention of hepatic encephalopathy in older adults. Protein restriction of 0.6 g/kg/d has traditionally been used as medical nutrition therapy in liver cirrhosis. However, recent evidence has shown that protein restrictions have many negative consequences for older adults with cirrhosis. Current research indicates protein intakes of 1.2-1.5 g/ kg/d in liver cirrhosis; however, many older adults do not consume this amount. Strategies to help increase protein intake and manage cirrhosis include ensuring adequate protein at every meal through either regular intake or supplementation, protein supplementation prior to bedtime or overnight, and supplementation with branchedchain amino acids. An emphasis on vegetable protein versus animal protein is probably not an advantageous treatment option because of lack of conclusive evidence regarding benefits and potential negative side effects. and progression of chronic liver disease and cirrhosis.There are several different factors that naturally occur in older adulthood that help contribute to the development of chronic liver disease and cirrhosis. After reaching maximum size in early adulthood, the liver steadily decreases in both size and the amount of blood flow it receives, leading to decreased function and efficiency over time [10] . Also, increased ammonia production and bacterial overgrowth are common in older adulthood, both of which are thought to play a key role in development of hepatic encephalopathy [11] . Older adults tend to have chronic constipation, intestinal dysmotility, and increased colonic transit time, which predisposes them to increased ammonia production [12] . Finally, older adulthood is associated with a higher incidence of diabetes, which is strongly correlated to progression of liver cirrhosis [13] . Pathogenesis of malnutrition in older adults with cirrhosisIt is estimated that 20% of patients with compensated cirrhosis and 60% of patients with decompensated cirrhosis have malnutrition [14] . In older adults, protein energy malnutrition is associated with high health care costs, increased frequency of infection and bedsores, increased morbidity and mortality, and poor physical functioning [4,5] . In canine trials, poor nutritional status has been shown to encourage the development of hepatic encephalopathy [15] . In addition, malnutrition in cirrhosis is positively associated with old age [14] . Multiple factors help contribute to the development of malnutrition in older adults with cirrhosis, including inadequate intake, altered absorption, sarcopenia, and altered metabolism. All causes must be explored and taken into consideration when developing treatment and prevention strategies.In older adults, food intake naturally decreases over time [16] , which promotes the development of malnutri...

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Section: Branched Chain Amino Acid Supplementation In Older Adults Wimentioning

confidence: 72%

Protein Recommendations for Older Adults with Cirrhosis: A Review

Iiames

Logomarsino

2015

Journal of Gastroenterology and Hepatology Research

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“…A meta-analysis of more recent trials has given some support to the use of BCAAs in reducing all manifestations of HE with the supposition that BCAAs boost ammonia uptake and metabolism within skeletal muscle. BCAAs have also been proposed as an aide in the transport of ammonia nitrogen directly out of neurons (Gluud et al 2013(Gluud et al , 2015. There is no role whatsoever in protein restriction in the management of acute or chronic HE.…”

Section: Therapeutic Strategies Targeting the Gut-liver-brain Axismentioning

confidence: 99%

Clinical science workshop: targeting the gut-liver-brain axis

et al. 2015

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A clinical science workshop was held at the ISHEN meeting in London on Friday 11th September 2014 with the aim of thrashing out how we might translate what we know about the central role of the gut-liver-brain axis into targets which we can use in the treatment of hepatic encephalopathy (HE). This review summarises the integral role that interorgan ammonia metabolism plays in the pathogenesis of HE with specific discussion of the roles that the small and large intestine, liver, brain, kidney and muscle assume in ammonia and glutamine metabolism. Most recently, the salivary and gut microbiome have been shown to underpin the pathophysiological changes which culminate in HE and patients with advanced cirrhosis present with enteric dysbiosis with small bowel bacterial overgrowth and translocation of bacteria and their products across a leaky gut epithelial barrier. Resident macrophages within the liver are able to sense bacterial degradation products initiating a pro-inflammatory response within the hepatic parenchyma and release of cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-8 into the systemic circulation. The endotoxemia and systemic inflammatory response that are generated predispose both to the development of infection as well as the manifestation of covert and overt HE. Co-morbidities such as diabetes and insulin resistance, which commonly accompany cirrhosis, may promote slow gut transit, promote bacterial overgrowth and increase glutaminase activity and may need to be acknowledged in HE risk stratification assessments and therapeutic regimens. Therapies are discussed which target ammonia production, utilisation or excretion at an individual organ level, or which reduce systemic inflammation and endotoxemia which are known to exacerbate the cerebral effects of ammonia in HE. The ideal therapeutic strategy would be to use an agent that can reduce hyperammonemia and reduce systemic inflammation or perhaps to adopt a combination of therapies that can address both.

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“…It concluded that, oral BCAA supplements improve manifestations of HE but have no effect on survival. 41 However its role in management of HE still needs more data to use in higher grade of HE.…”

Section: Branched Chain Amino Acidmentioning

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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Oral Branched-Chain Amino Acids Have a Beneficial Effect on Manifestations of Hepatic Encephalopathy in a Systematic Review with Meta-Analyses of Randomized Controlled Trials

Cited by 100 publications

References 35 publications

Protein Recommendations for Older Adults with Cirrhosis: A Review

Protein Recommendations for Older Adults with Cirrhosis: A Review

Clinical science workshop: targeting the gut-liver-brain axis

Management of Overt Hepatic Encephalopathy

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