Efficacy of Zinc Supplement in Minimal hepatic Encephalopathy: A prospective, Randomized Controlled Study (Zinc-MHE Trial).

BACKGROUND: Minimal hepatic encephalopathy (MHE) in patients with cirrhosis of the liver has a negative impact on the quality of daily life by impairing attention, memory and visuomotor coordination, and resulting in cognitive decline. Ammonia is thought to be part of the pathogenesis of hepatic encephalopathy. Zinc is an essential trace element, one of the cofactor enzymes that is essential for the conversion of ammonia to urea. AIM: To assess the effect of zinc supplementation on psychomotor performance in cirrhotic patients with MHE. METHODS: This prospective, randomized, controlled trial recruited 69 cirrhotic patients (age 18-75 years) diagnosed with MHE by neuropsychometric (NP) tests comprised of the number connection test part A (NCT-A), number connection test part B (NCT-B), serial dot test (SDT), line tracing test (LTT) and digit symbol test (DST). Eligible patients were randomly assigned (1:1) by a computer-based system block of four randomizations to receive 45 mg of elemental zinc or placebo for 12 weeks. The primary endpoint was the absolute change in NP tests from baseline to 12-weeks of zinc supplement compared with placebo. The assessment of changes of the health-related quality of life (HRQOL) using the Short Form survey-36 (SF-36) questionnaire, as well as biochemical parameters including serum ammonia, was also conducted in both groups. RESULTS: From January to December 2020, 125 eligible cirrhotic patients were diagnosed with liver cirrhosis, of whom 69 (55%) had MHE and were randomly assigned to treatment: 35 patients were assigned to receive 45 mg of elemental zinc and the others 34 patients to receive placebo. Significant improvements in NP tests were established in the zinc supplement group when compared with the placebo group (NCT-A, p = 0.029; NCT-B, p = 0.008; SDT, p = 0.002; DST, p = <0.001). A significant improvement of HRQOL assessed by the SF-36 score was only seen in the zinc group (p<0.001). In the zinc supplement group, not only was an improvement in psychomotor performance reported, but quality of life was also improved, irrespective of baseline zinc level. CONCLUSION: Twelve weeks of zinc supplement in cirrhotic patients with MHE not only had a positive effect on psychomotor performance but also improved HRQOL irrespective to baseline zinc level.

Probiotics combined with rifaximin influence the neurometabolic changes in a rat model of type C HE.

Type C hepatic encephalopathy (HE) is a neuropsychiatric disease caused by chronic liver disease. Management of type C HE remains an important challenge because treatment options are limited. Both the antibiotic rifaximin and probiotics have been reported to reduce the symptoms of HE, but longitudinal studies assessing their effects on brain metabolism are lacking and the molecular mechanisms underpinning their effects are not fully understood. Therefore, we evaluated in detail the effects of these different treatments on the neurometabolic changes associated with type C HE using a multimodal approach including ultra-high field in vivo 1H MRS. We analyzed longitudinally the effect of rifaximin alone or in combination with the probiotic Vivomixx on the brain metabolic profile in the hippocampus and cerebellum of bile duct ligated (BDL) rats, an established model of type C HE. Overall, while rifaximin alone appeared to induce no significant effect on the neurometabolic profile of BDL rats, its association with the probiotic resulted in more attenuated neurometabolic alterations in BDL rats followed longitudinally (i.e. a smaller increase in Gln and milder decrease in Glu and Cr levels). Given that both rifaximin and some probiotics are used in the treatment of HE, the implications of these findings may be clinically relevant.

Dietary Interventions in Liver Cirrhosis.

Liver cirrhosis is associated with significant nutritional risks that often result in serious hepatic complications and poor survival rates. Diet is an important but underutilized aspect in the treatment modality of cirrhosis. Therefore, the aims of this review are to ascertain nutritional risks associated with its pathophysiology and to summarize existing evidence that support dietary recommendations for managing this patient population. Alterations in substrate utilization for energy production is a main feature of liver cirrhosis, resulting in increased catabolism of protein stores and a predisposition toward protein-energy malnutrition, even in the early stages of the disease. The body of evidence suggests that a high energy and protein (>1.2 g/kg body weight/d) diet consumed frequently and late in the evening is effective in improving nutritional status of these patients and has been associated with improved hospitalization and mortality rates. The use of branched-chain amino acid supplementation shows promise in reducing cirrhosis-related complications but are currently limited by adverse gastrointestinal symptoms and poor palatability. Furthermore exploration of dietary manipulation of branched-chain amino acid warrants further examination. Evidence is also accumulating that protein intake should not be restricted in patients with hepatic encephalopathy with earlier studies of protein restriction neglecting to account for the relative increase in fermentable fiber which would reduce the absorption of ammonia into the portal system in a way similar to supplementation with lactulose. Finally, a major finding of this review is the need to improve the quality and quantity of dietary intervention studies for patients with liver cirrhosis, particularly with the use of partial or whole dietary sources. In conclusion, dietary management of cirrhosis is not a one-size fits all approach but should be implemented earlier on in the treatment algorithm to improve the clinical prognosis of cirrhosis.

Medium-chain triglycerides supplement therapy with a low-carbohydrate formula can supply energy and enhance ammonia detoxification in the hepatocytes of patients with adult-onset type II citrullinemia.

Citrin, encoded by SLC25A13, constitutes the malate-aspartate shuttle, the main NADH-shuttle in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). Citrin deficiency is predicted to impair hepatic glycolysis and de novo lipogenesis, resulting in hepatic energy deficit. Secondary decrease in hepatic argininosuccinate synthetase (ASS1) expression has been considered a cause of hyperammonemia in CTLN2. We previously reported that medium-chain triglyceride (MCT) supplement therapy with a low-carbohydrate formula was effective in CTLN2 to prevent a relapse of hyperammonemic encephalopathy. We present the therapy for six CTLN2 patients. All the patients' general condition steadily improved and five patients with hyperammonemic encephalopathy recovered from unconsciousness in a few days. Before the treatment, plasma glutamine levels did not increase over the normal range and rather decreased to lower than the normal range in some patients. The treatment promptly decreased the blood ammonia level, which was accompanied by a decrease in plasma citrulline levels and an increase in plasma glutamine levels. These findings indicated that hyperammonemia was not only caused by the impairment of ureagenesis at ASS1 step, but was also associated with an impairment of glutamine synthetase (GS) ammonia-detoxification system in the hepatocytes. There was no decrease in the GS expressing hepatocytes. MCT supplement with a low-carbohydrate formula can supply the energy and/or substrates for ASS1 and GS, and enhance ammonia detoxification in hepatocytes. Histological improvement in the hepatic steatosis and ASS1-expression was also observed in a patient after long-term treatment.

Management of Hepatic Encephalopathy: A Primer.

OBJECTIVE: To review the management of hepatic encephalopathy (HE), including lifestyle modifying strategies and pharmacological interventions. DATA SOURCES: A literature search of PubMed through March 2016 was conducted utilizing the keywords hepatic encephalopathy, ammonia, and cirrhosis All published articles evaluating treatments for HE were considered. STUDY SELECTION AND DATA EXTRACTION: Available English-language data from reviews, abstracts, presentations, and clinical trials of the treatment of HE in humans were reviewed; relevant clinical data were selected and included. DATA SYNTHESIS: HE is a prevalent complication of portal hypertension and cirrhosis that results in altered mental status and neuropsychiatric impairment. Although the pathogenesis has not been elucidated, numerous treatment options exist. This review will explore the role of dietary interventions and supplements, including use of zinc, acetyl-l-carnitine, and probiotics, in the management of HE. Additionally, the use of various ammonia-lowering agents will be evaluated. The nonabsorbable disaccharides represent first-line therapies for the management and prophylaxis of HE; rifaximin use has been demonstrated to be effective for both treatment and prophylaxis of HE symptoms, with use relegated to those patients who fail to respond to or tolerate the nonabsorbable disaccharides. In light of toxicities associated with the use of neomycin and metronidazole, recent guidelines recommend both as alternatives for the treatment of HE, with the use of vancomycin discouraged. CONCLUSION: Although numerous treatment options are available, management of HE remains a clinical challenge. Additional research is needed to explore the pathogenesis and better understand the role of pharmacotherapy in managing this condition.

Probiotics in management of hepatic encephalopathy.

Gut microflora leads to production of ammonia and endotoxins which play important role in the pathogenesis of hepatic encephalopathy (HE). There is relationship between HE and absorption of nitrogenous substances from the intestines. Probiotics play a role in treatment of HE by causing alterations in gut flora by decreasing the counts of pathogen bacteria, intestinal mucosal acidification, decrease in production and absorption of ammonia, alterations in permeability of gut, decreased endotoxin levels and changes in production of short chain fatty acids. Role of gut microbiota using prebiotics, probiotics and synbiotics have been evaluated in the management of minimal hepatic encephalopathy (MHE), overt HE and prevention of HE. Many studies have shown efficacy of probiotics in reduction of blood ammonia levels, treatment of MHE and prevention of HE. However these trials have problems like inclusion of small number of patients, short treatment durations, variability in HE/MHE related outcomes utilized and high bias risk, errors of systematic and random types. Systematic reviews also have shown different results with one systematic review showing clinical benefits whereas another concluded that probiotics do not have any role in treatment of MHE or HE. Also practical questions on optimal dose, ideal combination of organisms, and duration of treatment and persistence of benefits on long term follow-up are still to be clarified. At present, there are no recommendations for use of probiotics in patients with HE.

What is new about diet in hepatic encephalopathy.

There is a relationship between hepatic encephalopathy (HE) protein malnutrition and muscle wasting. Muscle may play an alternative role in ammonia detoxification. Molecular mechanisms responsible for muscle depletion are under investigation. Specific nutrients may interact to reverse the molecular pathways involved in muscle wasting at an early stage. Training exercises have also been proposed to improve skeletal muscle mass. However, these data refer to small groups of patients. The amelioration of muscle mass may potentially help to prevent HE. The pathogenesis of HE is associated with modifications of the gut microbiota and diet is emerging to play a relevant role in the modulation of the gut milieu. Vegetarian and fibre-rich diets have been shown to induce beneficial changes on gut microbiota in healthy people, with reduction of Bacteroides spp., Enterobacteriaceae, and Clostridium cluster XIVa bacteria. By way of contrast, it has been suggested that a high-fat or protein diet may increase Firmicutes and reduce Bacteroidetes phylum. Milk-lysozyme and milk-oligosaccharides have also been proposed to induce a "healthy" microbiota. At present, no studies have been published describing the modification of the gut microbiota in cirrhotic patients with HE as a response to specific diets. New research is needed to evaluate the potentiality of foods in the modulation of gut microbiota in liver disease and HE.

Nutritional support for fulminant hepatitis / Soporte nutricional para la hepatitis fulminante

Introduction: fulminant hepatitis (FH) is associated with exacerbated hypercatabolism, hypoglycemia and hyperammonemia that are accompanied by the release of proinflammatory cytokines and catabolic hormones into the systemic circulation worsening patient’s clinical condition. Nutritional support is a crucial element for the recovery of these patients. Objectives: the aim of this review is to update Nutritional Support for Fulminant Hepatitis. Methods: the review was performed using electronic search on Medline-PubMed using Mesh-terms. Results and discussion: there are not many data available on nutritional support to fulminant hepatitis or acute liver failure. Strategies for initial nutritional intervention are focused on the control of the previously described FH metabolic derangements, and should be individualized according to the severity of patient’s clinical condition. Energy and protein can be provided in amounts of 25-40 kcal/kg/day and 0.8-1.2 g/kg/day, respectively. Enteral nutrition therapy is indicated for patients with advancing encephalopathy or for those who cannot be properly fed orally. Euglycemia must be achieved and protein intake can be based on BCAA formulae. Lipids can be administered as energy supplementation with caution. Adequate nutrition therapy can potentially reduce morbidity and mortality of FH patients (AU)

Introducción: la hepatitis fulminante se asocia a un exacerbado hipercatabolismo, la hipoglicemia y la hiperamonemia están acompañadas por la liberación de citocinas proinflamatorias y hormonas catabólicas en la circulación sistémica, empeorando la condición clínica del paciente. El apoyo nutricional es un elemento crucial para la recuperación de estos pacientes. Objetivos: el objetivo de esta revisión es actualizar el apoyo nutricional para la hepatitis fulminante. Métodos: la revisión se llevó a cabo mediante la búsqueda electrónica en Medline-PubMed, utilizando malla de términos. Resultados y discusión: no hay muchos datos disponibles sobre el apoyo nutricional para la hepatitis fulminante o fallo hepático agudo. Las estrategias de intervención nutricional inicial se centran en el control de los trastornos metabólicos de la hepatitis fulminante descritos anteriormente, que deben ser individualizadas de acuerdo a la gravedad de la situación clínica del paciente. Energía y proteína se pueden proporcionar en cantidades de 25-40 kcal/kg/día y 0,8-1,2 g /kg/día, respectivamente. La terapia nutricional enteral está indicada en pacientes con encefalopatía avanzada o para aquellos que no pueden ser adecuadamente alimentados por vía oral. Se debe obtener una euglicemia y la ingesta de proteínas puede estar basada en fórmulas de BCAA. Los lípidos se pueden administrar como suplemento energético con precaución. Una terapia nutricional adecuada puede potencialmente reducir la morbilidad y la mortalidad de los pacientes con hepatitis fulminante (AU)

Diets in Encephalopathy.

As many as 80% of patients with end-stage liver disease and hepatic encephalopathy have significant protein-calorie malnutrition. Because of the severe hypercatabolic state of cirrhosis, the provision of liberal amounts of carbohydrate (at least 35 to 40 kcal/kg per day), and between 1.2 and 1.6 g/kg of protein is necessary. Protein restriction is not recommended. Branched-chain amino acid supplementation and vegetable protein are associated with improved outcomes. Dietary supplementation with vitamins, minerals (with the notable exception of zinc) and probiotics should be decided on a case-by-case basis.

Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial.

BACKGROUND & AIMS: Little is known about whether probiotics can affect outcomes of patients with cirrhosis and hepatic encephalopathy (HE). We assessed the efficacy of a probiotic preparation in preventing the recurrence of HE (primary outcome) and reducing the number of hospitalizations and severity of liver disease in patients with cirrhosis. METHODS: We performed a double-blind trial at a tertiary care hospital in India. Patients with cirrhosis who had recovered from an episode of HE during the previous month were assigned randomly (using computer-generated allocation) to groups given a probiotic preparation (VSL#3, 9 × 10(11) bacteria; CD Pharma India Private Limited, New Delhi, India) (n = 66) or placebo (n = 64) daily for 6 months. RESULTS: There was a trend toward a reduction in the development of breakthrough HE among patients receiving the probiotic (34.8% in the probiotic group vs 51.6% in the placebo group; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.38-1.11; P = .12). Fewer patients in the probiotic group were hospitalized for HE (19.7% vs 42.2%, respectively; HR, 0.45; 95% CI, 0.23-0.87; P = .02) or for complications of cirrhosis (24.2%) than in the placebo group (45.3%) (HR, 0.52; 95% CI, 0.28-0.95; P = .034). Child-Turcotte-Pugh and model for end-stage liver disease scores improved significantly from baseline to 6 months in the probiotic group, but not in the placebo group. There were no adverse events related to VSL#3. CONCLUSIONS: Over a 6-month period, daily intake of VSL#3 significantly reduced the risk of hospitalization for HE, as well as Child-Turcotte-Pugh and model for end-stage liver disease scores, in patients with cirrhosis. ClinicalTrials.gov number: NCT01110447.

Dietary management of hepatic encephalopathy revisited.

PURPOSE OF REVIEW: The burden of hepatic encephalopathy on health services is increasing, and some degree of consensus in relation to drug therapy and prophylaxis has been reached. This review focuses on the role of nutritional interventions in the management of hepatic encephalopathy. RECENT FINDINGS: A number of relatively new pieces of evidence are emerging in relation to nutrition and hepatic encephalopathy as follows: first, reduction of protein intake is not useful for hepatic encephalopathy, but protein selection should be considered; second, oral supplementation with branched chain amino acids has a role not only for its nutritional effect in cirrhosis per se, but also for its effect in reducing the risk of recurrence of hepatic encephalopathy; third, alterations in gut microbiota develop in parallel with decompensation of cirrhosis, and modulation of gut microbiota may be effective for treating and preventing hepatic encephalopathy; fourth, prebiotics and probiotics are potentially useful in this aim, thus further research or trials on prebiotics and probiotics are required; fifth, micronutrient deficiency, which is common in end-stage liver disease, has adverse effects on the brain and may either directly cause encephalopathy per se, or interact with the mechanisms leading to hepatic encephalopathy. SUMMARY: Properly performed nutritional interventions are likely to be useful for patients with hepatic encephalopathy, but well conducted clinical trials are required. VIDEO ABSTRACT: http://links.lww.com/COCN/A7.

Evidence of a vicious cycle in glutamine synthesis and breakdown in pathogenesis of hepatic encephalopathy-therapeutic perspectives.

There is substantial clinical and experimental evidence that ammonia is a major factor in the pathogenesis of hepatic encephalopathy. In the article is demonstrated that in hepatocellular dysfunction, ammonia detoxification to glutamine (GLN) in skeletal muscle, brain, and likely the lungs, is activated. In addition to ammonia detoxification, enhanced GLN production may exert beneficial effects on the immune system and gut barrier function. However, enhanced GLN synthesis may exert adverse effects in the brain (swelling of astrocytes or altered neurotransmission) and stimulate catabolism of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in skeletal muscle. Furthermore, the majority of GLN produced is released to the blood and catabolized in enterocytes and the kidneys to ammonia, which due to liver injury escapes detoxification to urea and appears in peripheral blood. As only one molecule of ammonia is detoxified in GLN synthesis whereas two molecules may appear in GLN breakdown, these events can be seen as a vicious cycle in which enhanced ammonia concentration activates synthesis of GLN leading to its subsequent catabolism and increase in ammonia levels in the blood. These alterations may explain why therapies targeted to intestinal bacteria have only a limited effect on ammonia levels in patients with liver failure and indicate the needs of new therapeutic strategies focused on GLN metabolism. It is demonstrated that each of the various treatment options targeting only one the of the ammonia-lowering mechanisms that affect GLN metabolism, such as enhancing GLN synthesis (BCAA), suppressing ammonia production from GLN breakdown (glutaminase inhibitors and alpha-ketoglutarate), and promoting GLN elimination (phenylbutyrate) exerts substantial adverse effects that can be avoided if their combination is tailored to the specific needs of each patient.

Papel de la nutrición en la encefalopatía hepática: es tiempo de cambiar / Role of nutrition in hepatic encephalopathy: time to change

La presencia de desnutrición es frecuente en los pacientes con cirrosis hepática (CH), siendo un factor de riesgo que aumenta la mortalidad y la posibilidad de desarrollar descompensaciones clínicas. Es necesario conocer el grado de desnutrición de estos pacientes para valorar la indicación de una intervención nutricional y su eficacia, siendo la medida de la fuerza de prensión de la mano mediante dinamometría una prueba adecuada a tal fin. El desarrollo de Encefalopatía Hepática (EH) constituye una situación relevante en la historia natural de la CH que precisa una serie de medidas terapéuticas, incluida la intervención nutricional. Entre las medias nutricionales destaca un adecuado aporte energético diario (35-40 Kcl/Kg de peso) y proteico (1.2-1.5 gramos/Kg de peso), debiendo desechar la utilización de dietas hipoproteicas que solo pueden agravar la desnutrición sin presentar efectos beneficiosos sobre la EH. Por otro lado se recomiendan pequeñas ingestas distribuidas uniformemente a lo largo del día y la utilización de una colación nocturna con carbohidratos complejos, así como la promoción de una dieta rica en vegetales y fibra. Otras medidas como los aminoácidos de cadena ramificada o los probióticos no cuentan actualmente con la suficiente evidencia científica para su uso en la EH (AU)

Malnutrition is common in patients with liver cirrosis being a risk factor that increases mortality and the possibility of developing clinical decompensation. It´s important to know the degree of malnutrition in these patients to assess the indication of a nutritional intervention and its effectiveness. Hand grip dynamometer is a suitable test for this purpose. Development of Hepatic Encephalopathy is a relevant situation in the natural history of cirrhosis that requires a number of therapeutic measures, including nutritional intervention. It´s recommended to obtain an adequate daily energy intake (35-40 Kcl / Kg body weight) and protein intake (1.2-1.5 g / kg body weight) and must avoid hipoprotein diets which only aggravate malnutrition and they don´t have beneficial effects on EH. In the other hand, it’s recommended small intakes distributed throughout the day and the use of a late evening snack with complex carbohydrates, as well as the promotion of a diet rich in vegetables and fiber. The use of branched-chain amino acids or probiotics do not currently have sufficient scientific evidence for use in HE (AU)

The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus.

UNLABELLED: Nitrogen metabolism plays a major role in the development of hepatic encephalopathy (HE) in patients with cirrhosis. Modulation of this relationship is key to the management of HE, but is not the only nutritional issue that needs to be addressed. The assessment of nutritional status in patients with cirrhosis is problematic. In addition, there are significant sex-related differences in body composition and in the characteristics of tissue loss, which limit the usefulness of techniques based on measures of muscle mass and function in women. Techniques that combine subjective and objective variables provide reasonably accurate information and are recommended. Energy and nitrogen requirements in patients with HE are unlikely to differ substantially from those recommended in patients with cirrhosis per se viz. 35-45 kcal/g and 1.2-1.5g/kg protein daily. Small meals evenly distributed throughout the day and a late-night snack of complex carbohydrates will help minimize protein utilization. Compliance is, however, likely to be a problem. Diets rich in vegetables and dairy protein may be beneficial and are therefore recommended, but tolerance varies considerably in relation to the nature of the staple diet. Branched chain amino acid supplements may be of value in the occasional patient intolerant of dietary protein. Increasing dietary fiber may be of value, but the utility of probiotics is, as yet, unclear. Short-term multivitamin supplementation should be considered in patients admitted with decompensated cirrhosis. Hyponatremia may worsen HE; it should be prevented as far as possible and should always be corrected slowly. CONCLUSION: Effective management of these patients requires an integrated multidimensional approach. However, further research is needed to fill the gaps in the current evidence base to optimize the nutritional management of patients with cirrhosis and HE.

Importancia de la nutrición en enfermos con encefalopatía hepática / Importance of nutritional support in patients with hepatic encephalopathy

La desnutrición es una complicación frecuente que influye negativamente en el pronóstico del enfermo con cirrosis hepática. La disminución de la ingesta junto con la aparición de diversas alteraciones endocrino-metabólicas condicionan un estado hipercatabólico que precisa de un mayor aporte energético. Una de las complicaciones que puede aparecer en la fase de cirrosis descompensada es la encefalopatía hepática. El reconocido papel del amonio en la patogenia de la encefalopatía hepática ha condicionado durante muchos años una restricción en el aporte de proteínas de estos enfermos. Sin embargo, no existe evidencia de que una dieta baja en proteínas mejore el curso de la encefalopatía hepática y sí de que empeore el estado nutricional y favorezca la aparición de distintas complicaciones relacionadas con la desnutrición. En este trabajo, se revisa el uso de aminoácidos ramificados y de proteínas de diferente origen, probióticos y simbióticos, antioxidantes, L-Ornitina-L-Aspartato, acetil-L-carnitina en enfermos con encefalopatía hepática (AU)

Protein calorie malnutrition is frequently a complication in the chronic liver disease patient and is considered to be a negative prognostic factor. Anorexia and several other endocrine metabolic complications produce an hypermetabolic state that needs more caloric intake. Hepatic encephalopathy is one of the developments possible in patients with descompensated cirrhosis. The wellknown role of ammonia in the pathogenesis of hepatic encephalopathy has determined a restriction in dietary protein along many decades. Nevertheless, there is no evidence about a low protein diet being better in the outcome of hepatic encephalopathy, it worsens, moreover, the nutritional status and helps in the development of many nutritional related complications. This article reviews the use of oral branched-chain amino acids and proteins of different sources, probiotics, synbiotics, antioxidants, oral L-Ornithine L-Aspartate and acetyl-L-carnitine in patients with hepatic encephalopathy (AU)

Low-protein diets for hepatic encephalopathy debunked: let them eat steak.

Hepatic encephalopathy (HE) is an incompletely understood phenomenon and serves as a poor prognosis in patients with cirrhosis. Confusion from HE can affect the ability to eat adequately. Despite the prevalence of malnutrition in cirrhotic patients in the 1950s, it was reported that bouts of overt HE were controlled with low protein intake. This largely uncontrolled observation led to restriction of protein intake in cirrhotic patients with or without HE and was an accepted standard of care for many decades to follow. Published in 2004, the pivotal article "Normal Protein Diet for Episodic Hepatic Encephalopathy: Results of a Randomized Study" by Cordoba and colleagues was the first controlled study randomizing cirrhotic patients with HE to receive different amounts of dietary protein. At the completion of the study, the authors concluded that a normal-protein diet was safe and did not exacerbate HE. The Cordoba study suggests that low-protein diets should be abandoned. In light of this evidence, nutrition guidelines have proposed that protein restriction should be avoided in patients with HE as protein requirements are increased in cirrhosis. Despite the advice of experts in the field, it has been shown in recent years that some physicians still believe that protein restriction is needed in patients with HE. This belief has not been substantiated in controlled studies, and societal recommendations have changed. There is no real evidence documenting the advantages of protein restriction in HE. On the contrary, Cordoba and colleagues' article has shown that there are disadvantages to restricting protein in HE.

Diet and cognition in chronic liver disease.

PURPOSE OF REVIEW: The spectrum of neurocognitive impairment in cirrhosis spans a continuum of minimal hepatic encephalopathy (MHE) to overt hepatic encephalopathy (OHE), the pathophysiology of which remains incompletely understood. The current available evidence, however, suggests that nutrition plays an important role in its development and points to the fact that malnutrition increases the morbidity and mortality of patients with cirrhosis. This review incorporates recent findings published in the last 2 years within the evolution of evidence regarding the role dietary manipulation can play in the comprehensive management of patients with cirrhosis and cognitive dysfunction. RECENT FINDINGS: In patients with cirrhosis it is important to prevent starvation physiology which occurs after few hours of caloric deprivation as compared to 3 days in noncirrhotics. This can be accomplished by making sure that cirrhotic patients have daily breakfast and a late evening snack. In addition, probiotics and symbiotics are well tolerated and improve cognitive function in patients with MHE. SUMMARY: The long-time held belief that protein restriction is needed to improve encephalopathy has no scientific basis but remains widely practiced. Branched-chain amino acids supplement may be helpful in patients who continue to suffer from OHE despite treatment of precipitating events and pharmacologic treatment with lactulose and rifaximin. Preventing starvation physiology and supplementing the diet with prebiotics and symbiotics are helpful in patients with MHE.

Nutritional support in the treatment of chronic hepatic encephalopathy.

The prevalence of under nutrition in cirrhotic patients is 61% and it usually progresses as the disease becomes more advanced. The deterioration in the nutritional status and its associated metabolic derangements has raised doubts about the benefits of severe and prolonged protein restriction as a treatment for hepatic encephalopathy. However, the practice of dietary protein restriction for patients with liver cirrhosis is deeply embedded among medical practitioners and dietitians. To date, no solid conclusions may be drawn about the benefit of protein restriction. However, the negative effects of protein restriction are clear, that is, increased protein catabolism, the release of amino acids from the muscle, and possible worsening of hepatic encephalopathy. In conclusion, chronic protein restriction causes progressive and harmful protein depletion and must be avoided.