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.

Beneficial health effects of low-digestible carbohydrate consumption.

Low-digestible carbohydrates represent a class of enzyme-resistant saccharides that have specific effects on the human gastrointestinal tract. in the small bowel, they affect nutrient digestion and absorption, glucose and lipid metabolism and protect against known risk factors of cardiovascular disease. In the colon they are mainly degraded by anaerobic bacteria in a process called fermentation. As a consequence, faecal nitrogen excretion is enhanced, which is used clinically to prevent or treat hepatic encephalopathy. Low-digestible carbohydrates are trophic to the epithelia of the ileum and colon, which helps to avoid bacterial translocation. Short-chain fatty acids are important fermentation products and are evaluated as new therapeutics in acute colitis. They are considered in the primary prevention of colorectal cancer. The bifidogenic effect of fructo-oligosaccharides merits further attention, Unfermented carbohydrates increase faecal bulk and play a role in the treatment of chronic functional constipation, symptomatic diverticulosis and, possibly, the irritable bowel syndrome. In conclusion, low-digestible carbohydrates may play a role in the maintenance of human digestive health. However, the strength of evidence differs between disease entities.

Effects of a branched-chain amino acid-enriched diet on chronic hepatic encephalopathy in dogs.

A decreased ratio of branched-chain amino acids (BCAA) to aromatic amino acids (AAA) is considered an important pathogenetic factor in hepatic encephalopathy (HE). A relationship between the deranged BCAA/AAA ratio and dopaminergic dysfunction through the formation of "false" neurotransmitters has been postulated. The intermediate lobe of the pituitary is more pronounced in dogs than in humans and because it is primarily under dopaminergic inhibitory influence, it may serve as an indicator of alterations in dopaminergic neurotransmission. We investigated the effects of a diet with a high BCAA/AAA ratio (HR) and an isonitrogenous diet with a low BCAA/AAA ratio (LR) on several physical and biochemical parameters including pituitary function in dogs with portocaval shunts and 40% hepatectomy and in sham-operated pair-fed controls, in a double-blind, randomized cross-over study. Portocaval-shunted dogs had hyperammonemia (33+/-3 microM (mean +/- SEM) before and 214+/-21 after surgery)) and signs of HE. Their BCAA/AAA ratio in plasma and CSF decreased from 4.3+/-0.3 and 2.3+/-0.3 before surgery to 1.3+/-0.1 and 0.5+/-0.1 after surgery, respectively. These parameters remained unaltered in the control dogs. The consumption of the LR diet was significantly higher than consumption of the HR diet. In the portocaval-shunted dogs, plasma ammonia concentration was higher on the HR diet than on the LR diet (344+/-52 v 246+/-45) and the HE grade was worse. The BCAA/AAA ratio remained abnormal in HE dogs during the feeding of both diets. The basal and haloperidol-stimulated release of alpha-melanotropin and cortisol in plasma were not significantly different between or within groups during any period. In contrast, urinary cortisol excretion was increased in the HE dogs after surgery (urinary cortisol:creatinine ratio (x10(-6)) 8.5+/-1.4 before and 30.4+/-8.9 after surgery). The basal plasma concentration of adrenocorticotropin in HE dogs was decreased after surgery (68.3+/-10.2 ng/L before and 40.8+/-4.4 after surgery). This indicates a non-pituitary-dependent hyperresponsiveness of the adrenals. We conclude from these results that chronic HE in dogs is not associated with an abnormal dopaminergic neurotransmission at least at the level of the pituitary, and that it is not the content of the dietary neutral amino acids but rather the total protein intake that may have a beneficial effect on HE.

[Intake of essential trace elements (selenium, copper and iron) in the nutrition of patients hospitalized with liver cirrhosis]. / Apports en oligo-éléments essentiels (sélénium, cuivre et fer) dans l'alimentation des cirrhotiques hospitalisés.

Dietary intake for three essential trace elements: selenium, copper and iron was studied in hospitalized patients receiving either ordinary meals or regimens adapted for liver cirrhosis. The aim of the study was to assess the effects of dietary manipulations: reduction in sodium intake for uncomplicated disease and protein restriction to 40 g per day in patients with hepatic encephalopathy. The meals proposed to these three groups were collected during fourteen days and daily intake for three elements was estimated by direct analysis of the assembled meals of the day. Dietary selenium was greatly affected by the restriction in protein intake contrary to copper and iron which were not significantly reduced. Moreover, overall daily trace element intake was rather low and clearly less than the most recent recommended allowances for these essential elements. Relationships between deficiency in some of these trace elements and worsening of the liver disease have been partly documented. They should encourage studies on the correction of dietary intake.

Lactic acid bacteria and human health.

Although claims for health and nutritional benefits have been made for lactic acid bacteria in fermented dairy products for nearly a century, the nutritional and therapeutic value of these organisms is still controversial. This article will review the scientific basis of these claims. There are numerous studies showing fermentation of food with lactobacilli increase the quantity, availability, digestibility, and assimilability of nutrients. The basis for this conclusion comes from direct measurements of vitamin synthesis and from increased feed efficiency when fermented products are fed to animals. There have been a number of studies showing that various fermented dairy products lower serum cholesterol levels in humans and animals. These studies are reviewed and the validity of these findings are assessed. A summary of the evidence indicating that lactase deficient individuals can eat yogurt and the mechanisms involved in this toleration is reviewed. The role of fermented dairy products in inhibiting tumor growth and chemically induced tumors in animals is discussed and the possible mechanisms involved in this protective effect are reviewed. Fermented dairy products and lypholized lactobacilli preparations have been shown to be useful in treating and preventing various intestinal infections including; salmonellosis, shigellosis and antibiotic induced diarrhea. In this context a specific lactobacillus designated GG has been shown to be useful in treating recurring diarrhea caused by a toxin produced by Clostridium difficile.

Dietoterapia em enfermidades hepáticas / Diet therapy in liver diseases

O fígado exerce papel fundamental na metabolizaçäo de vários nutrientes. Discute-se, inicialmente, aspectos do metabolismo de: hidratos de carbono, lípides, proteínas, vitaminas e minerais. O efeito das enfermidades hepáticas no estado nutricional e seus respectivos mecanismos säo apresentados. Dentro da terapêutica das hepatopatias o item "dieta" assume papel preponderante. Esta tem por finalidade a prevençäo e o restabelecimento de alteraçöes nutricionais do organismo como um todo e a recuperaçäo da funçäo normal das células hepáticas alteradas. Säo revisados aspectos dietoterápicos do tratamento de formas agudas e crônicas. Comenta-se em detalhe o mecanismo e as propostas terapêuticas em situaçöes de encefalopatia hepática. Desta forma, apresentam-se as modificaçöes da dieta normal como tratamento dirigido às alteraçöes específicas da funçäo metabólica do órgäo

Hepatopedal flow restoration in patients intolerant of total portal diversion.

This report describes an experience with operative restoration of hepatopedal portal blood flow in five patients intolerant of total splanchnic shunting. Portal flow was reestablished by takedown of the total shunt and construction of a selective, distal splenorenal shunt, or by isolation and arterialization of the hepatic limb of the shunted portal vein. In two patients, shunt revision was undertaken electively for chronic encephalopathy, which had been unresponsive to low-protein diet, intestinal antibiosis and oral lactulose. Eighteen and 48 months after operation, both patients have had no encephalopathy on an unrestricted protein intake, and work actively as homemakers. Needle liver biopsies showed enhanced mitotic activity in the early postoperative period, suggesting hepatocyte regeneration. In three patients, shunt conversion or arterialization was undertaken in desperate circumstances, characterized by liver failure (bilirubin greater than 10 mg/dl, albumin less than 2.5 g/dl, prothrombin time greater than 16 sec), coma, and respirator dependency. Although the patients showed immediate, marked improvement in mentation, all three died of intraabdominal hemorrhage in the first few postoperative days, in spite of maximum blood product support. Two conclusions can be drawn from this limited experience: (1) at a time of election, restoration of hepatopedal portal flow can be accomplished with considerable benefit in patients with side-to-side portacaval or hemodynamically equivalent shunts, and (2) similar procedures in patients with fulminant liver failure are unlikely to succeed.

Total parenteral nutrition with F080 in cirrhotics with subclinical encephalopathy.

It has been proposed that hepatic encephalopathy and malnutrition in cirrhosis can be reversed by infusion of a protein formula (F080) enriched with branched-chain amino acids (valine, leucine, isoleucine) and containing decreased amounts of aromatic amino acids (phenylalanine, tyrosine, tryptophan). This hypothesis was tested by measuring changes in encephalopathy status, plasma ammonia, amino acid profile, and liver function during seven metabolic balance studies in three patients with cirrhosis and subclinical encephalopathy given increasing amounts (20-100 g/d) of F080. The results showed the following: 1) positive nitrogen balance was achieved only with 80 and 100 g F080/day; 2) plasma ammonia fell during negative, but increased during positive nitrogen balance; 3) plasma tyrosine and cystine fell significantly (p less than 0.05) with all intakes of F080; 4) the abnormal branched-chain to aromatic amino acid ratio was reversed; 5) extracellular volume was expanded in all patients; 6) albumin, bilirubin, prothrombin time became abnormal; and 7) encephalopathy did not significantly change from baseline. It is concluded that, in this population, F080 is an inadequate nutritional formula when given as the sole protein source because it produces hypotyrosinemia and hypocystinemia. The marked changes in the ratio of branched-chain to aromatic amino acids are not accompanied by improvement in encephalopathy.

Comparison of the effects of Hepatic-Aid and a Casein modular diet on encephalopathy, plasma amino acids, and nitrogen balance in cirrhotic patients.

Hepatic-Aid is purported to ameliorate encephalopathy and promote positive nitrogen balance in protein-intolerant, cirrhotic patients by correcting their imbalanced amino acid profile. This study evaluated Hepatic-Acid by comparing a 50-g Casein diet with an identical diet with 20-g Casein/30-g Hepatic-Aid per day in a cross-over study. Four patients with biopsy-proven stable cirrhosis, encephalopathy, and under-nutrition were studied. Each study period included three days of equilibration and eight days of metabolic balance, with the following measured at baseline and on balance days 5 and 8: routine biochemistry, fasting ammonia, psychometric tests, EEG, and plasma amino acid profiles. There was no significant change in clinical status, routine biochemistry, fasting ammonia, psychometrics or EEG between the two study periods. Mean (+/-SD) nitrogen balance on the Casein diet at 1.5 +/- 1.5 g/day was not significantly different from that on the Hepatic-Aid diet at 1.5 +/- 1.2 g/day. Plasma amino acid profiles showed a significant fall (p less than 0.05) in fasting and intraprandial tyrosine (tyr) and phenylalanine (phe) on Hepatic-Aid, but only intraprandial leucine (leu), isoleucine (ile), and valine (val) were significantly increased (p less than 0.05) on Hepatic-Aid. The ratio leu + ile + val to tyr + phe was significantly increased (p less than 0.05) on Hepatic-Aid. It is concluded that Hepatic-Aid, as given in this study, maintains N balance similar to Casein, alters the amino acid profile towards normal, but does not ameliorate encephalopathy.

Effect of dietary protein manipulation in subclinical portal-systemic encephalopathy.

Eight stable cirrhotic patients with mild or subclinical portal-systemic encephalopathy (PSE) were studied after shunt surgery when they were off all antiencephalopathic therapy. Equal amounts of mixed proteins were alternated with animal or vegetable protein in a crossover protocol under metabolic conditions for five consecutive, one week periods. The different dietary periods were not associated with either a change in the neurological impairment score or the Trailmaking Tests, which showed a learning effect. The peak frequencies of the computer analysed EEG (CAEEG) were lower during the animal (6.58 +/- 0.42 Hz) than the vegetable (7.10 +/- 0.44 Hz) diet (p 0.01). Neither arterial ammonia levels nor plasma amino acid ratios changed with the diets, whereas urinary 3-methyl-histidine excretion increased during the animal diet. During the vegetable diet the apparent nitrogen balance tended to be more positive than during either the mixed or animal diets associated with decrease in the urinary nitrogen excretion. The peak frequency of the CAEEG is the most sensitive test to monitor methods of treatment in portal-systemic encephalopathy. A vegetable protein diet, rather than overall protein restriction, should be considered in the management of this disorder, particularly when the nutritional state is poor.