The role of nutrition in hepatic encephalopathy

PURPOSE OF REVIEW: Protein-calorie malnutrition may be observed in all clinical stages of liver disease. Nutritional management in these patients is imperative. It is crucial that protein intake is not restricted ad hoc. Administration of vegetable proteins for patients who cannot tolerate standard proteins and, if necessary, branched-chain amino acid-enriched formulae can be an option to these patients. This issue, however, remains controversial. RECENT FINDINGS: This study is an update on the nutritional management of hepatic encephalopathy based on several studies of the last decades, involving dietary protein intake and branched-chain amino acid supplementation. SUMMARY: Malnutrition is a common complication of liver disease and it adversely affects patient outcome. Inadequate dietary protein intake has a very deleterious effect on hepatic encephalopathy, nutritional status, and clinical outcome in these patients and must be avoided. The administration of branched-chain amino acids stimulates hepatic protein synthesis, reduces postinjury catabolism and therefore improves nutritional status. Conflicting results in various different trials, however, exist, and this issue remains unclear.     

Role of branched-chain amino acids in liver disease: the evidence for and against

PURPOSE OF REVIEW: There is ample evidence that patients with liver disease have an ongoing energy and protein catabolism. Nutritional management in these patients must receive high priority. The administration of branched-chain amino acids to patients with liver disease has been a controversial subject. This review is an update on the data available from various studies involving branched-chain amino acids supplementation in patients with chronic liver disease and associated complications. RECENT FINDINGS: This review summarizes the results of nutritional interventions involving branched-chain amino acids supplementation carried out in different centres around the world. It is interesting to note that no toxic effects of branched-chain amino acids supplementation have been reported in any of these trials. SUMMARY: Administration of branched-chain amino acids stimulates hepatic protein synthesis in patients with chronic liver disease and this could contribute significantly to improving their nutritional status, and result in a better quality of life. The beneficial role of branched-chain amino acids supplementation in patients with chronic hepatic encephalopathy has been clearly documented in some studies but the exact mechanism of action is still not clear.     

Nutrition and alcoholic liver disease

While the rate of malnutrition is relatively modest in alcoholic patients without alcoholic liver disease, the rate of malnutrition is virtually 100% in patients with alcoholic hepatitis and/or alcoholic cirrhosis. The reasons for malnutrition in the alcoholic hepatitis patient include various factors such as anorexia, poor diet, malabsorption, and altered metabolic state. When the patient is hospitalized, the malnutrition frequently worsens because of fasting for tests, continued anorexia, and complications such as gastrointestinal bleeding. Patients with severe acute hepatitis appear to be both hypermetabolic and hypercatabolic, whereas data are much more conflicting concerning patients with more stable liver disease. Most studies suggest that patients with alcoholic liver disease require at least 60 g of protein per day to maintain positive nitrogen balance. Consistent alterations in plasma amino acid profiles occur in alcoholic liver disease, and specialized nutritional formulations have been devised to correct this amino acid profile with the intent of improving overall nutritional status, hepatic encephalopathy, and mortality. The effects of nutritional support (including use of specialized products) on outcome, on acute hepatic encephalopathy, and on chronic or latent portal systemic encephalopathy are reviewed.     

New support for branched-chain amino acid supplementation in advanced hepatic failure

Nutritional supplementation with branched-chain amino acids (BCAA) has been a topic of considerable debate for more than two decades. Several studies have demonstrated that supplementation with BCAA is associated with improvement of the catabolic state commonly seen in people with cirrhosis, whereas other studies have showed an improvement in portosystemic encephalopathy in patients with liver disease. Some studies have also shown there to be no benefit in BCAA supplementation in advanced cirrhosis. A recent large clinical trial showed that long-term BCAA supplementation may be useful in preventing progressive hepatic failure and improving liver function in some patients.     

Confusion and abnormal liver enzyme levels: problems with diagnosing hepatic encephalopathy

3 patients with liver failure developed hepatic encephalopathy. 2 patients, men aged 60 and 72 years, had chronic liver disease and presented with episodes of confusion. They recovered after being treated with lactulose. The third patient, a 37-year-old woman, became comatose shortly after the onset of acute liver failure due to acute autoimmune hepatitis. She died before a suitable donor liver became available. Hepatic encephalopathy is a syndrome of potential reversible neurological symptoms. Especially in the early stages of the condition, hepatic encephalopathy can be difficult to diagnose. Patients may present with mild cognitive impairment or episodes characterized by neurological symptoms. Hepatic encephalopathy is a clinical diagnosis. The pathophysiologic mechanism is only partly understood but toxicity of ammonia on the central nervous system seems to be of major importance. Raised ammonia concentrations or EEG findings consistent with metabolic encephalopathy may support but are not essential to the diagnosis. Episodes of hepatic encephalopathy are often elicited by an underlying disease such as infection or gastro-intestinal bleeding. It is important to recognize hepatic encephalopathy in its early stages because adequate treatment of the condition and any underlying disease reduces morbidity and mortality.     

Effect of oral amino acid supplementation on liver disease after jejunoileal bypass for morbid obesity.

Previous work in our laboratory and others suggests that protein malnutrition plays an important role in the pathogenesis of hepatic steatosis and dysfunction which characteristically appears after jejunoileal bypass for morbid obesity. Postoperative protein-calorie malnutrition is at least in part a consequence of diminished intestinal absorption of free amino acids. In an attempt to prevent liver disease, six morbidly obese patients were orally supplemented with essential amino acids for 4 months after surgery. Oral amino acid supplementation only partially influenced protein malnutrition and had no effect on deterioration of hepatic morphology and dysfunction. Although this mode of therapy appears to be ineffective in preventing postoperative liver abnormalities, other studies suggest that oral oligopeptide supplementation and parenteral administration of amino acids are beneficial. In addition to protein deificiency, other factors which may contribute to the development of liver disease are reviewed.     

A paleolithic diet is more satiating per calorie than a mediterranean-like diet in individuals with ischemic heart disease

Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure.     

Nutritional assessment in various stages of liver cirrhosis

OBJECTIVES: The aims of this study were to determine the prevalence of protein-calorie malnutrition, characteristics, and clinical importance of nutrition disorders in patients with liver cirrhosis according to severity of disease. METHODS: Nutrition assessments such as subjective global assessment, anthropometric and biochemical measurements, immunocompentency, thiamin and riboflavin status in 60 patients with cirrhosis (33 male and 27 female) were recorded between June 1999 and December 1999 at an outpatient clinic at Ramathibodi Hospital, Bangkok, Thailand. The origin of liver disease was alcohol related in 50% of patients. Child-Pugh criteria were used to establish the severity of liver disease. RESULTS: In terms of energy malnutrition, 13.3% of patients had ideal body weights below 90% and 11.7% had body mass indexes below 18.5 kg/m(2). Protein malnutrition (low albumin) and immunoincompetence (abnormal response to skin tests) were found much more frequently (45% and 22%) than energy malnutrition. Patients with alcoholic cirrhosis had ascites (P < 0.05) and hepatic encephalopathy (P < 0.001) more frequently and less triceps skinfold thickness than those with non-alcoholic cirrhosis. Subjective global assessment and serum proteins correlated with the degree of liver-function impairment, but immunologic tests correlated inversely in cirrhosis patients. Mean values for creatinine-height index, hemoglobin, cholesterol, and complement C4 showed significant decreases in severe liver failure (Child-Pugh class C) only in patients with alcoholic cirrhosis (P < 0.05). Malnutrition was correlated with the clinical severity of liver disease. CONCLUSIONS: The study showed that protein-energy malnutrition is a common complication of liver cirrhosis. Nutritional disorders appeared to be related to the degree of liver injury and the etiology of nutritional disorders. Nutritional disorders were more severe with alcoholic cirrhosis than with non-alcoholic cirrhosis.     

Amino Acid Profile in Malnourished Patients with Liver Cirrhosis and Its Modification with Oral Nutritional Supplements: Implications on Minimal Hepatic Encephalopathy

Low plasma levels of branched chain amino acids (BCAA) in liver cirrhosis are associated with hepatic encephalopathy (HE). We aimed to identify a metabolic signature of minimal hepatic encephalopathy (MHE) in malnourished cirrhotic patients and evaluate its modification with oral nutritional supplements (ONS) enriched with ß-Hydroxy-ß-methylbutyrate (HMB), a derivative of the BCAA leucine. Post hoc analysis was conducted on a double-blind placebo-controlled trial of 43 individuals with cirrhosis and malnutrition, who were randomized to receive, for 12 weeks, oral supplementation twice a day with either 220 mL of Ensure^® Plus Advance (HMB group, n = 22) or with 220 mL of Ensure^® Plus High Protein (HP group, n = 21). MHE evaluation was by psychometric hepatic encephalopathy score (PHES). Compared to the HP group, an HMB-specific treatment effect led to a larger increase in Val, Leu, Phe, Trp and BCAA fasting plasma levels. Both treatments increased Fischer’s ratio and urea without an increase in Gln or ammonia fasting plasma levels. MHE was associated with a reduced total plasma amino acid concentration, a reduced BCAA and Fischer´s ratio, and an increased Gln/Glu ratio. HMB-enriched ONS increased Fischer´s ratio without varying Gln or ammonia plasma levels in liver cirrhosis and malnutrition, a protective amino acid profile that can help prevent MHE.     

Protein intake in renal and hepatic disease

The kidney and the liver play a central role in protein metabolism. Synthesis of albumin and other proteins occurs mainly in the liver, whereas protein breakdown and excretion are handled through an intricate interaction between these two organ systems. Thus, disease states of either the liver and/or the kidney invariably result in clinically relevant disturbances of protein metabolism. Conversely, metabolic processes regulated by these two organs are directly affected by dietary protein intake. Of particular importance in this respect is the maintenance of acid/base homeostasis. Finally, both the amount and composition of ingested proteins have a direct impact on renal function, especially in a state of diseased kidneys. Consequently, dietary protein intake is of paramount importance in patients with chronic nephropathy and renal insufficiency. Limitation of ingested protein, particularly from animal sources, is crucial in order to slow the progression of chronic kidney disease and impaired renal function. In contrast, patients with chronic renal failure undergoing renal replacement therapy by hemodialysis or peritoneal dialysis, have an increased protein demand. The syndrome of "protein-energy malnutrition" is a relevant factor for morbidity and mortality in this population and requires early detection and vigorous treatment. Protein intake in patients with cirrhosis of the liver should not be diminished as has been earlier suggested but rather increased to 1.0 - 1.2 g/kg body weight/day, in order to prevent protein malnutrition. Moderate restriction depending on protein tolerance (0.5 - 1.2 g/kg body weight/day), with the possible addition of branched chain amino acids (BCAA), has been recommended only in patients with advanced hepatic encephalopathy. Proteins of plant origin are theoretically superior to animal proteins.     

Three targets of branched-chain amino acid supplementation in the treatment of liver disease

The article explains the pathogenesis of disturbances in branched-chain amino acid (BCAA; valine, leucine, and isoleucine) and protein metabolism in various forms of hepatic injury and it is suggested that the main cause of decrease in plasma BCAA concentration in liver cirrhosis is hyperammonemia. Three possible targets of BCAA supplementation in hepatic disease are suggested: (1) hepatic encephalopathy, (2) liver regeneration, and (3) hepatic cachexia. The BCAA may ameliorate hepatic encephalopathy by promoting ammonia detoxification, correction of the plasma amino acid imbalance, and by reduced brain influx of aromatic amino acids. The influence of BCAA supplementation on hepatic encephalopathy could be more effective in chronic hepatic injury with hyperammonemia and low concentrations of BCAA in blood than in acute hepatic illness, where hyperaminoacidemia frequently develops. The favorable effect of BCAA on liver regeneration and nutritional state of the body is related to their stimulatory effect on protein synthesis, secretion of hepatocyte growth factor, glutamine production and inhibitory effect on proteolysis. Presumably the beneficial effect of BCAA on hepatic cachexia is significant in compensated liver disease with decreased plasma BCAA concentrations, whereas it is less pronounced in hepatic diseases with inflammatory complications and enhanced protein turnover. It is concluded that specific benefits associated with BCAA supplementation depend significantly on the type of liver disease and on the presence of inflammatory reaction. An important task for clinical research is to identify groups of patients for whom BCAA treatment can significantly improve the health-related quality of life and the prognosis of hepatic disease.     

Correlation between electroencephalogram, hepatic encephalopathy grade, and biochemical indices in beagles with portacaval anastomosis

The EEG, grades of hepatic encephalopathy, and biochemical indices of 16 beagles with portacaval anastomosis were recorded throughout their lives and correlations between these parameters were investigated. The degree of deterioration of some biochemical indices, such as the ammonia concentration, glutamate oxaloacetate transaminase and alkaline phosphatase activities in the plasma, and percentage loss of body weight showed a progressive increase parallel to the severity of the hepatic encephalopathy (HE) grade (grading scale O-IV), but other biochemical indices such as the concentrations of aromatic or branched-chain amino acids, the molar ratio of branched-chain to aromatic amino acids, or the total protein concentration in the plasma did not show such relationship. The SW ratio, an index of the incidence of slow-waves in the EEG, was calculated from frequency distribution histograms which were obtained by frequency analyses of EEG recordings. A slight but significant correlation was found between the SW ratio and the plasma ammonia concentration. In addition, the SW ratio consistently increased with increase in the HE grade, although the SW ratio in HE grade IV was below the normal range for beagles. These results show that only the ammonia concentration in the plasma correlates with deterioration of the HE grade and of the SW ratio, suggesting that changes in ammonia concentration in the plasma should be of diagnostic value in assessing changes in mental state and the EEG in patients with liver cirrhosis. The importance of ammonia in pathogenesis of HE is stressed.     

Nutritional support after liver transplantation: a randomized prospective study

Nutritional support in patients with advanced cirrhosis is difficult due to protein, fluid and salt restrictions. Successful liver transplantation should improve nutrient tolerance. We randomly assigned 28 hypoalbuminemic cirrhotic patients to receive, immediately after liver transplantation, one of three regimens: group 1, no nutritional support (n = 10); group 2, total parenteral nutrition (TPN) (35 kcal/kg/day) with standard amino acids (1.5 g/kg/day) (n = 8); or group 3, isocaloric isonitrogenous TPN with added branched-chain amino acids (n = 10). Therapy was continued for 7 days posttransplant. Jaundice resolution was unaffected by nutritional support. Nitrogen balance favored both TPN groups. Branched-chain amino acid (BCAA) aromatic amino acid ratios were highest in group 3. Coma scores and serum ammonia levels were similar in all groups. Both TPN groups achieved respirator independence earlier; this difference was not statistically significant. Group 1 patients stayed longest in ICU; the difference was statistically significant. TPN with either standard or BCAA- enriched amino acids is tolerated well immediately after successful liver transplant. Positive nitrogen balance is achieved; large protein loads do not worsen encephalopathy. Nutritional support may improve respiratory muscle function, allowing earlier weaning from ventilatory support. A shortened length of ICU stay justifies the expense of TPN.     

General and specialized parenteral amino acid formulations for nutrition support

Advances in the understanding of amino acid metabolism and of the interaction of amino acids with skeletal muscle, liver, brain, and other tissues have led to refinements of parenteral amino acid solutions. Clinical situations may dictate the use of specific amino acid formulations. Branched-chain amino acid (BCAA) solutions may normalize aberrant amino acid profiles in patients with hepatic encephalopathy; however, controlled trials demonstrate little effect on clinical outcome, and the effectiveness in patients with acute liver failure or undergoing orthotopic liver transplantation is unproved. BCAA solutions have also been tried in septic and severely stressed patients with equivocal results. Renal failure has been treated with essential amino acid solutions, yet low-dose standard amino acid formulations are probably equally effective. Pediatric preparations have been tailored to "normalize" amino acid profiles to those of healthy term, breast-fed neonates. Recent studies suggest that premature infants receiving these formulations may achieve intrauterine growth rates, although the effect on long-term outcome is unknown. Glutamine may be essential for the preservation of intestinal mucosal structure and function; further study is indicated to determine the necessity of adding glutamine to parenteral amino acid solutions. Recently, amino acid infusions have been associated with enhanced ventilatory drive, possibly via stimulation of central ventilatory mechanisms. A variety of other side effects have been documented, including acidosis, hyperammonemia, hypercalciuria, and possibly bone disease and hepatotoxicity. Further understanding of the metabolism of intravenous infusion of amino acids is necessary to provide optimal nutritional protein support. Because full information regarding the complex effects of intravenous substrates is lacking, special amino acid formulations must be used with caution.     

Protein consumption and hepatic encephalopathy in alcoholic hepatitis. VA Cooperative Study Group #275.

Patients with alcoholic hepatitis frequently have moderate or severe malnutrition. Dietary protein intake may be restricted in these patients because of concurrent hepatic encephalopathy. To further evaluate the relationship between dietary protein intake and hepatic encephalopathy in alcoholic hepatitis, we evaluated prospectively gathered data from a study of 136 placebo-treated patients with moderate or severe alcoholic hepatitis conducted at eight Department of Veterans Affairs Medical Centers.

Physical examination, laboratory tests, and grade of hepatic encephalopathy were recorded at entry and every seventh day for the first 28 days of study. Average daily protein intake was calculated from dietary evaluation obtained by a registered dietitian at entry and again three times a week.

Sixty-three percent of patients had hepatic encephalopathy at entry. Hepatic encephalopathy decreased over time. Time dependent regression analysis found low protein intake, along with high blood urea nitrogen (BUN) and high serum creatinine, to be independently associated with worsening hepatic encephalopathy. Similar analysis found low BUN and less malnutrition at entry into the study to be independently associated with improved hepatic encephalopathy. Higher protein intake was associated with improved hepatic encephalopathy in univariate (p = 0.01), but not multivariate, analysis.

In patients with alcoholic hepatitis who can be treated with standard anti-encephalopathy medications (e.g., lactulose and neomycin), low protein intake is associated with worsening hepatic encephalopathy while a higher protein intake correlates with improvement in hepatic encephalopathy.     

A Comprehensive Review Evaluating the Impact of Protein Source (Vegetarian vs. Meat Based) in Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a common neurological consequence in patients with cirrhosis and has a healthcare burden of USD 5370 to 50,120 per patient annually. HE significantly hampers the quality of life and is a major cause of morbidity and mortality. Patients with cirrhosis are at a high risk for protein-calorie malnutrition due to altered metabolism. Current evidence has changed the old belief of protein restriction in patients with cirrhosis and now 1.2 to 1.5 g/kg/day protein intake is recommended. Case series and studies with small numbers of participants showed that a vegetarian protein diet decreases the symptoms of HE when compared to a meat-based diet, but the evidence is limited and requires further larger randomized controlled trials. However, vegetable or milk-based protein diets are good substitutes for patients averse to meat intake. Branch chain amino acids (BCAA) (leucine, isoleucine and valine) have also been shown to be effective in alleviating symptoms of HE and are recommended as an alternative therapy in patients with cirrhosis for the treatment of HE. In this review, we provide an overview of current literature evaluating the role of protein intake in the management of HE in cirrhosis.     

Conditional deficiencies of ornithine or arginine

Relative deficiencies of ornithine or arginine occur in the presence of excessive ammonia, excessive lysine, growth, pregnancy, trauma, or protein deficiency and malnutrition. Ammonia excess may occur in the presence of a normal liver when amino acid mixtures lacking ornithine, arginine, or citrulline are infused; when specific amino acids such as glycine are injected; when ammonium salts, urea, or urease are injected; or when the gastrointestinal tract contains an excess of protein, urea, or NH4+, as occurs after a gastrointestinal hemorrhage. In these states, ornithine is often rate-limiting for urea cycle function. Ornithine is also rate-limiting when ammonia excess occurs in the presence of hepatic failure. In three of the inherited urea cycle disorders, ornithine insufficiency and ammonia excess also occur. These disorders are citrullinemia, argininosuccinic aciduria, and argininemia. In the presence of excessive lysine the availability of arginine is reduced and the formation of ornithine is decreased in the liver; urea synthesis is reduced, but orotic acid synthesis is increased, and orotic aciduria results as carbamyl phosphate is directed toward the pyrimidine pathway. Hereditary lysinuric protein intolerance results in ornithine depletion, hyperammonemia, and orotic acid uria. Optimal growth in several species of animals requires 0.4-1.0% arginine in the diet. Diets deficient in arginine are associated with poor wound healing as well as stunted growth. The measurement of orotic acid excretion has been a convenient indicator of insufficiency of ornithine or arginine during growth or pregnancy in animals and should prove useful in assessing the requirement for arginine after trauma. Normal human pregnancy is associated with low-grade orotic aciduria. Protein deficiency and malnutrition increase the vulnerability of the animal or child to ammonia toxicity. This is presumably due to insufficient ornithine for normal urea cycle responsiveness.     

Conditional deficiencies of ornithine or arginine.

Relative deficiencies of ornithine or arginine occur in the presence of excessive ammonia, excessive lysine, growth, pregnancy, trauma, or protein deficiency and malnutrition. Ammonia excess may occur in the presence of a normal liver when amino acid mixtures lacking ornithine, arginine, or citrulline are infused; when specific amino acids such as glycine are injected; when ammonium salts, urea, or urease are injected; or when the gastrointestinal tract contains an excess of protein, urea, or NH4+, as occurs after a gastrointestinal hemorrhage. In these states, ornithine is often rate-limiting for urea cycle function. Ornithine is also rate-limiting when ammonia excess occurs in the presence of hepatic failure. In three of the inherited urea cycle disorders, ornithine insufficiency and ammonia excess also occur. These disorders are citrullinemia, argininosuccinic aciduria, and argininemia. In the presence of excessive lysine the availability of arginine is reduced and the formation of ornithine is decreased in the liver; urea synthesis is reduced, but orotic acid synthesis is increased, and orotic aciduria results as carbamyl phosphate is directed toward the pyrimidine pathway. Hereditary lysinuric protein intolerance results in ornithine depletion, hyperammonemia, and orotic acid uria. Optimal growth in several species of animals requires 0.4-1.0% arginine in the diet. Diets deficient in arginine are associated with poor wound healing as well as stunted growth. The measurement of orotic acid excretion has been a convenient indicator of insufficiency of ornithine or arginine during growth or pregnancy in animals and should prove useful in assessing the requirement for arginine after trauma. Normal human pregnancy is associated with low-grade orotic aciduria. Protein deficiency and malnutrition increase the vulnerability of the animal or child to ammonia toxicity. This is presumably due to insufficient ornithine for normal urea cycle responsiveness.     

Conséquences de l'insuffisance rénale aiguë sur les métabolismes

Acute renal failure (ARF) is associated with a number of metabolic disturbances. ARF does not seem by itself to cause significant alterations of energy expenditure. It induces insulino-resistance and an increase in hepatic gluconeogenesis, which contribute to glucose intolerance. Disturbances of protein metabolism lead to hypercatabolism due to underlying diseases and to renal failure. These abnormalities are linked to ARF-induced metabolic acidosis or to renal failure per se (secretion of catabolic hormones, decrease in muscle protein synthesis, decrease in amino acid production from the kidney, protein losses due to dialysis). Finally ARF is associated with disturbances of lipid metabolism: decrease in lipolytic activity, increase in triglyceridemia, hypocholesterolemia and alterations of lipoprotein profile.These metabolic disturbances can induce malnutrition, which may contribute to the high mortality of ARF. However, assessing the proper role of renal failure remains difficult, and requires further prospective studies using multivariate analysis.     

Role of nutrition in liver transplantation for end-stage chronic liver disease

Patients with end-stage liver disease often reveal significant protein-energy malnutrition, which may deteriorate after listing for transplantation. Since malnutrition affects post-transplant survival, precise assessment must be an integral part of pre- and post-surgical management. While there is wide agreement that aggressive treatment of nutritional deficiencies is required, strong scientific evidence supporting nutritional therapy is sparse. In practice, oral nutritional supplements are preferred over parenteral nutrition, but enteral tube feeding may be necessary to maintain adequate calorie intake. Protein restriction should be avoided and administration of branched-chain amino acids may help yield a sufficient protein supply. Specific problems such as micronutrient deficiency, fluid balance, cholestasis, encephalopathy, and comorbid conditions need attention in order to optimize patient outcome.