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Ger Med Sci. 2009; 7: Doc12.
Published online Nov 18, 2009. doi:  10.3205/000071
PMCID: PMC2795384
Hepatology – Guidelines on Parenteral Nutrition, Chapter 16
M. Plauth,1 T. Schuetz,2 and Working group for developing the guidelines for parenteral nutrition of The German Association for Nutritional Medicine
1Dept. of Internal Medicine, Municipal Clinic Dessau, Germany
2Medical Department, Division of Gastroenterology, Hepatology and Endocrinology, Charité Universitätsmedizin Berlin, Germany
Received January 14, 2009
Parenteral nutrition (PN) is indicated in alcoholic steatohepatitis (ASH) and in cirrhotic patients with moderate or severe malnutrition. PN should be started immediately when sufficientl oral or enteral feeding is not possible. ASH and cirrhosis patients who can be sufficiently fed either orally or enterally, but who have to abstain from food over a period of more than 12 hours (including nocturnal fasting) should receive basal glucose infusion (2–3 g/kg/d). Total PN is required if such fasting periods last longer than 72 h. PN in patients with higher-grade hepatic encephalopathy (HE); particularly in HE IV° with malfunction of swallowing and cough reflexes, and unprotected airways. Cirrhotic patients or patients after liver transplantation should receive early postoperative PN after surgery if they cannot be sufficiently rally or enterally nourished. No recommendation can be made on donor or organ conditioning by parenteral administration of glutamine and arginine, aiming at minimising ischemia/reperfusion damage. In acute liver failure artificial nutrition should be considered irrespective of the nutritional state and should be commenced when oral nutrition cannot be restarted within 5 to 7 days. Whenever feasible, enteral nutrition should be administered via a nasoduodenal feeding tube.
Keywords: non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, liver cirrhosis, hepatic encephalopathy, acute liver failure
Indication and time of PN in ASH
  • PN is indicated in ASH and should be immediately started in ASH patients with moderate or severe malnutrition, who cannot be sufficiently fed either orally or enterally (A).
  • ASH patients who can be sufficiently fed either orally or enterally, but who have to abstain from food (including nocturnal fasting) for more then 12 hours should receive basal glucose infusion (2–3 g/kg/d) (C). Total PN is required if fasting periods last longer than 72 h (C).
The nutritional state of the patient carries a prognostic significance in patients with ASH (III) [1], [2], [3]. Simple bedside methods like “subjective global assessment” or anthropometry are sufficient to identify at-risk patients, and are, therefore, recommended [4].
PN supplementation to ad lib oral nutrition was studied in seven controlled trials using conventional amino acid solutions. The parenteral intake provided approximately 200–3000 kcal/d, including 35–130 g amino acids per day, and the oral intake ranged from 13 to 39 kcal/kg/d [5], [6], [7], [8], [9], [10], [11], [12], [13]. No change in mortality was observed with this approach. This may be due to the inclusion of patients with low risk and only moderate disease severity. Adverse effects of increased nitrogen intake were not observed, although sensitive methods, able to detect minor degrees of hepatic encephalopathy, were not used. The majority of studies reported an improvement in visceral protein compartment (serum prealbumin, transferrin, total protein, total lymphocyte count), used as a measure of the nutritional state. An improvement in liver function (galactose elimination, serum bilirubin) was also described.
A late evening carbohydrate snack resulted in an improvement in protein metabolism in cirrhotic patients [14], [15], [16]. Therefore, it is recommended that in the event of a long fasting duration, patients should receive a basal glucose intake equal to the endogenous hepatic glucose production [14], [15], [16]. It is known that even an overnight fast in cirrhotic patients results in depletion of glycogen stores and metabolic conditions similar to that after prolonged starvation in normal individuals.
Energy intake
  • In practice, an energy requirement equal to 1.3 times the basal metabolic rate, calculated by means of a formula, can be safely assumed for patients with ASH (C).
According to an older study [17], ASH patients are not different from healthy persons with regards to the relationship between measured and predicted resting energy expenditure. ASH patients, however, show higher energy consumption when correlated to their reduced muscle mass (creatinine excretion in 24 h urine).
When hydration status is normal, the actual weight should be used as body weight for the calculation of the basal metabolic rate with the help of a formula [18]. In patients with ascites, the ideal weight according to the body height should be used for calculations.
Substrate intake with total PN
  • Carbohydrates should be provided exclusively by glucose and cover 50–60% of non-protein energy requirements (C).
  • Lipids should be provided using emulsions with a reduced content of polyunsaturated fatty acids compared to pure soybean oil emulsions and cover 40–50% of non-protein energy requirements (C).
  • The amino acid intake should amount to 1.2 g/kg/d in patients who are either not malnourished or moderately malnourished, and 1.5 g/kg/d in severely malnourished patients (C).
  • Water-soluble and fat-soluble vitamins as well as minerals and trace elements should be administered daily (cf. “Water, electrolytes, vitamins and trace elements” (C).
These recommendations are based on those for PN in liver cirrhosis, which is already present in many cases of ASH. There are no systematic trials on the quantity and the formulation of PN for ASH.
Both water-soluble and fat-soluble vitamins should be administered daily in a standard TPN dosage. If necessary, administration of pharmacological doses of vitamin B1, as a therapy/prophylaxis for Wernicke’s encephalopathy, or of vitamin K in cholestasis-related fat malabsorption or other vitamins may be additionally required to correct deficiencies. Trace elements should be administered daily in a standard total PN dose. A pragmatic recommendation is to routinely administer double the daily requirements of zinc (=2x10 mg/d).
This patient group is at great risk of developing refeeding syndrome (cf. “Complications and monitoring” because of their tendency to be chronically malnourished.
Indication and time of PN in cirrhosis
  • Immediate commencement of PN is indicated in cirrhotic patients with moderate or severe malnutrition, who cannot be sufficiently nourished either orally or enterally (C).
  • Cirrhosis patients, who can be sufficiently nourished either orally or enterally, but who have to abstain temporarily from food (including nocturnal fasting) over a 12 hour period, should receive a basal glucose infusion (2–3 g/kg/d). Total PN is required if this fast lasts longer than 72 h (C).
  • PN should be considered in patients with higher-grade hepatic encephalopathy (HE); particularly in HE IV° with malfunction of swallowing and cough reflexes, and unprotected airways (C).
  • Cirrhosis patients should receive early postoperative (additional) PN after surgery, notwithstanding the recommendations for other patients, if they cannot be sufficiently nourished either orally or enterally (A).
  • After liver transplantation, patients should receive early postoperative nutrition. PN is the option second to enteral nutrition (C).
  • No recommendation can be made on the question of donor or organ conditioning, with the aim of minimising ischemia/reperfusion damage, by parenteral administration of glutamine and arginine (C).
Numerous descriptive studies have shown higher rates of complications and mortality in cirrhotic patients with marked signs of protein malnutrition as well as a higher mortality rate when subjected to liver transplantation [19], [20], [21], [22], [23], [24], [25], [26].
Prevalence and severity of malnutrition are independent of the aetiology of liver disease [20], [27], [28], but correlate positively with the severity of the illness. The prevalence of PEM increases from 20% in stage A, by Child-Pugh criteria, to over 60% in stage C [27]. The daily food intake is of prognostic significance. Cirrhosis patients with a low, spontaneous energy intake showed the highest mortality in controlled studies investigating the efficiency of supplementary enteral nutrition [2], [29], [30], [31], [32]. There are no systematic trials on PN in cirrhotic patients without ASH.
Simple bedside methods like “Subjective Global Assessment” or anthropometry were able to sufficiently identify malnutrition, and the use of more complex score systems was not superior in this identification [4].
The recommendation of basal glucose intake to be equal to endogenous hepatic glucose production in the event of longer fasting is based on the findings that a late evening carbohydrate snack results in an improvement in protein metabolism of cirrhotic patients [14], [15], [16]. After an overnight fast, in cirrhotic patients, glycogen stores are depleted and metabolic conditions are similar to that after prolonged starvation in normal individuals.
Hepatic Encephalopathy (HE). In patients with hepatic encephalopathy, oral nutrition is often insufficient, even in low-grade encephalopathy (HE I°–II°) due to somnolence and psycho-motor dysfunction, such that enteral feeding is required to provide adequate nutrition. PN should be considered in patients with higher-grade encephalopathy (HE), particularly in HE IV°, when there is malfunctioning of swallowing and cough reflexes in the presence of unprotected airways. In clinical practice, enteral nutrition in patients with acute liver failure [33] and the results of the study by Keohane et al. on malnourished patients with liver cirrhosis and acute encephalopathy [34] demonstrate the feasibility of enteral nutrition in comatose cirrhotic patients. There are no published systematic comparisons between enteral and parenteral nutrition in patients with liver cirrhosis and encephalopathy.
In malnourished cirrhotic patients, the risk of post-operative complications, including mortality, is increased after abdominal operations [35].
After visceral surgery, cirrhotic patients have a lower rate of complications when postoperative nutritional therapy is given instead of just fluid and electrolytes [36], [37] (Ib).
Surgery and Transplantation. Postoperative nutrition of transplant patients confers the advantage of shorter time on mechanical ventilation and shorter stay in the intensive care unit compared to just fluid and electrolyte infusions [38] (Ib). In a direct comparison between parenteral and early enteral nutrition, both strategies were equally efficient with regards to the maintenance of nutritional state [39]. However, lower incidence of viral infections, and improved nitrogen retention were observed in patients who had been given early enteral nutrition, 12 hours after the transplantation [40].
At present, the value of donor or organ conditioning, by means of high doses of arginine intake, with the aim of minimising ischemia/reperfusion damage is uncertain.
Energy intake
  • The energy requirement of many patients with liver cirrhosis amounts to 1.3 times the basal metabolic rate, calculated by means of a formula (B).
Measured resting energy expenditure is higher than predicted by the Harris Benedict formula in up to 30–35% of cirrhotic patients (hypermetabolism), and below the predicted value in 18% of the patients [41], [42]. Cirrhotic patients can also have a hypermetabolic state [43], defined as measured basal metabolic rate versus value calculated from measured body cell mass by regression analysis.
In order to classify patients according to metabolic rate, indirect calorimetry is required. Therefore, up to now these findings remain without consequence in clinical practice. Furthermore, the few publications on total energy expenditure in patients with liver cirrhosis indicate that the 24h energy requirement of cirrhotic patients is 130% of the basal metabolic rate [44], [45]. Diet-induced thermogenesis [46], [47], [48] and energy requirements for physical activity in stable cirrhosis patients [49], [50], [51] also show no deviation from those in healthy patients. Obviously, an increased energy requirement in advanced illness is compensated for by diminished physical activity reflecting poor physical condition [32], [51].
When hydration status is normal, the actual weight should be used as body weight for the calculation of the basal metabolic rate according to a formula [18]. In patients with ascites, the ideal weight according to body height should be used for calculations.
Patients with liver transplantations have average energy requirements similar to the majority of patients with major abdominal surgery. In these patients too, an intake of non-protein energy of 1.3-fold the basal metabolic rate is generally sufficient [52], [53]. In a longitudinal study, postoperative hypermetabolism peaked 10 days after the transplantation at 124% of the predicted basal metabolic rate [54]. There was no difference between measured and predicted basal metabolic rate at 6–12 months post transplantation [54], [55]. Hyperalimentation should be avoided.
Substrate intake – general
  • If PN is used as the exclusive form of nutrition, all necessary macro- and micro-nutrients must be administered with PN (C).
  • Carbohydrate intake should exclusively be provided by glucose and cover 50–60% of non-protein energy requirements (cf. “Carbohydrates” (C).
  • Lipid should be provided by using emulsions with a reduced content of polyunsaturated fatty acids, as compared to pure soy bean oil emulsions, and cover 40–50% of non-protein energy requirements (C).
  • PN-related hyperglycaemia should be consequently avoided (A).
  • A reduction in carbohydrate intake to 2–3 g/kg/d and continuous insulin administration, if needed, should be carried out in case of hyperglycaemia (C).
Insulin resistance in liver cirrhosis. In the fasting state, substrate utilisation is characterised by an increased rate of lipid oxidation and frequent occurrence of insulin resistance, even in Child-Pugh stage A of the illness [41], [56], [57], [58]. Insulin resistance induces reduced glucose uptake and dysfunctional non-oxidative glucose utilisation with reduced glycogen synthesis in skeletal muscles during fasting, while glucose oxidation and lactate production return to normal after glucose administration [47], [59], [60]. Some 15–37% of cirrhotic patients develop overt diabetes indicating an unfavourable prognosis [61], [62].
There is growing evidence of a treatment advantage in various clinical conditions when euglycaemia is maintained. It seems justified to also recommend this strategy for patients with liver cirrhosis who are receiving PN (cf. “Carbohydrates” and “Intensive medicine”
In the early postoperative phase, a dysfunction of glucose metabolism associated with insulin resistance is often prevalent. In this situation, hyperglycaemia should be treated by reducing the glucose intake, because higher insulin doses do not improve glucose oxidation [63].
When tacrolimus is used for immunosuppression, its diabetogenic potential can be lowered by reducing the dose and aiming for trough levels of 3–8 ng/ml without undue risk of rejection [64].
Lipid tolerance and MCT/LCT. Only few data are available on the ideal composition of the main energy-supplying substrates, carbohydrates and lipids. Plasma clearance and oxidation of infused lipids is normal in cirrhotic patients [65], [66]. Glucose and lipids have been used as energy-supplying substrates in a caloric ratio of 40–50: 50–60 (G:L) in two trials [67], [68]. There are findings suggesting more favourable substrate and metabolite concentrations when infusing both glucose and lipid compared to glucose as the sole energy substrate [69]. Improved functioning of the reticulo-endothelial system was observed (cf. “Surgery and transplantation” when using MCT/LCT emulsions (with a lower content of polyunsaturated fatty acids as compared to pure soy bean oil emulsions) after liver transplantation.
Substrate intake – amino acids
  • Amino acids should be administered in a dose of 1.2 g/kg/d in compensated cirrhosis without severe malnutrition, and in a dose of 1.5 g/kg/d in decompensated cirrhosis with severe malnutrition (A).
  • A standard solution should be given in encephalopathy ≤ grade II and a liver-adapted complete solution should be given in encephalopathy grades III–IV. These solutions contain an increased amount of branched-chain amino acids (BCAA) and lower content of aromatic amino acids, methionine and tryptophan (A).
Compensated cirrhosis. For PN, these patients do not require an amino acid solution with a special “hepatic formula” composition. In clinical studies, the protein or amino acid intake in patients with liver cirrhosis and severe encephalopathy was between 0.6 and 1.2 g/kg/d [70]. In patients with alcoholic hepatitis or cirrhosis with or without low-grade encephalopathy, the intake was between 0.5 and 1.6 g/kg/d [5], [6], [7], [9], [10], [11], [12], [13], [29], [30] [31], [71]. An explicit and systematic determination of the protein requirement has, however, been carried out only in a few studies. In these studies, patients with stable cirrhosis were found to have an increased protein requirement of 1.2 g/kg/d in contrast to the value of 0.8 g/kg/d in healthy humans [32], [44], [72], [73].
Cirrhosis with encephalopathy. Liver-adapted amino acid solutions containing increased proportions of branched-chain (35–45%) and a reduced proportion of aromatic amino acids as well as a reduced proportion of methionine and tryptophan have been introduced for patients with liver diseases [74], [75], [76] (Table 1 (Tab. 1)). These solutions help to correct the amino acid imbalance existing in liver cirrhosis. “Coma solutions” are available in some countries, which contain either exclusively BCAAs, or other additional substances supposed to be effective in hepatic encephalopathy. The solutions are incomplete, and, therefore, should only be used to target the pharmacological correction of an amino acid imbalance and not as the exclusive nitrogen source for PN.
Table 1
Table 1
Parenteral amino acid solutions with an increased content of branched-chain amino acids available in Germany
The effectiveness of branched-chain amino acids in the treatment of hepatic encephalopathy has been tested in seven controlled studies [77], [78], [79], [80], [81]; the results of which are, however, contradictory. It is extremely difficult to detect a treatment effect on hepatic encephalopathy, when at the same time complications of cirrhosis are present like gastrointestinal bleeding, sepsis or renal failure, which dominate the clinical results. A meta-analysis of these studies shows a beneficial effect of the BCAA-enriched solutions with regards to mental state, but not with regards to survival [70]. In a Cochrane analysis, a subgroup of the seven randomised controlled studies was analysed, with a total of 397 patients with acute hepatic encephalopathy, who were treated with intravenously administered BCAAs in the intervention group [82]. The parenteral BCAA administration had a significant positive effect on the improvement of hepatic encephalopathy; the period of survival, however, remained unchanged.
Surgery and transplantation. After liver resection, oesophagus transection with splenectomy or splenorenal shunt in patients with liver cirrhosis, no increased encephalopathy rate was observed when a conventional amino acid solution (50 g/24 h) was used for postoperative nutrition instead of a BCAA-enriched amino acid solution (40 g/24 h) [37]. No difference was observed between a standard or a BCAA-enriched amino acid solution after liver transplantation either [38].
Transplanted patients exhibit a noteworthy nitrogen loss with a continuously negative nitrogen balance up to 28 days post surgery [52], [83], therefore protein or amino acid intake should be increased appropriately. A protein or amino acid intake of 1.0–1.5 g/kg-/d was mostly used in studies [24], [38]. The determination of postoperative urea-nitrogen excretion was helpful in ascertaining individual nitrogen requirements.
Conditioning of organ donors. Data mainly derived from experimental studies indicate that the balanced nutrition of a “brain-dead” liver donor with moderate amounts of carbohydrates, lipids (long-chain fatty acids and possibly fish oil) and amino acids is associated with an improved function of the transplanted organ [84]. The value of donor or organ preconditioning against ischemia/reperfusion damage e.g. by means of high doses of arginine is at present uncertain.
Water, electrolytes, vitamins, trace elements
Patients with liver cirrhosis have profound alterations in body composition with an increase in total body water already in Child-Pugh stage A [85]. This goes along with salt retention, which does not manifest in hypernatraemia. In contrast, potassium, magnesium, phosphate and other intracellular minerals are frequently depleted.
No recommendations on the requirements of micronutrients can be made on the basis of controlled studies. The administration of micronutrients has no effect on the nutritional state other than in the adjustment of a deficiency.
Supplementations of zinc and vitamin A might indirectly improve the food intake and nutritional state by improving dysgeusia [86], [87]. Zinc and selenium deficiencies were observed in alcoholic and non-alcoholic liver disease [88], [89], [90], [91]. A striking association between hepatic encephalopathy and zinc deficiency has been described in case reports [92], [93]. Oral zinc supplementation, however, has shown no effectiveness in subclinical encephalopathy in controlled studies [94], [95], [96]. Urea production capacity increased after oral zinc supply when the previously lowered plasma levels were normalised [97].
A deficiency in water-soluble vitamins is common in cirrhosis, especially of alcoholic origin [98], [99]. Deficits in fat-soluble vitamins are observed in cholestasis-related steatorrhoea, bile salt deficiency and in alcoholics [100], [101]. Supplementation with calcium and vitamin D is recommended for patients with osteopenia, although this did not result in any improvement in bone density in patients with primary biliary cirrhosis, with oestrogen substitution proving to be much more effective in female patients [100], [102].
In practice, liberal supplementation is recommended in the first two weeks of treatment as the laboratory diagnosis of a specific trace element or vitamin deficiency may be more expensive. Due to high prevalence of malnutrition in this group of patients, they are in danger of developing re-feeding syndrome (cf. “Complications and monitoring”
After transplantation, the often chronic hyponatraemia should be corrected carefully in order to avoid the risk of pontine myelinosis [103]. It is recommended to regularly check magnesium levels in order to determine cyclosporine- or tacrolimus-induced hypomagnesaemia [104].
Some, but not all study groups, reported the risk of postoperative hypophosphataemia and its possible connection with PN following right hemihepatectomy in a living donor [105], [106], [107].
Due to the massive loss of liver cell function, acute liver failure is a serious condition characterised by profound metabolic dysfunctions and almost invariably complicated by multi-organ failure. Depending on the interval till the onset of hepatic encephalopathy (HE), hyperacute (onset of jaundice till HE <8 days), acute (interval <29 days) and sub-acute liver failure (interval 29–72 days) are distinguished [108]. Prognosis is more favourable in hyperacute LF (liver failure) than in acute or subacute LF.
Despite the clinical significance of metabolic derangements like hypoglycaemia or hyperammonaemia and encephalopathy, there is only scarce animal-experiment or physiologically descriptive data, and no published clinical studies, on which a metabolic intervention like nutritional therapy could be based.
Indication and time of PN
  • In analogy to intensive care patients, in acute LF artificial nutrition should be considered irrespective of the nutritional state and should be commenced when oral nutrition cannot be restarted within 5 to 7 days (cf. “Intensive medicine”
  • Whenever possible, enteral nutrition should be administered via a nasoduodenal feeding tube (C).
In the treatment of acute liver failure, measures to stabilize the metabolism and vital functions and the treatment of brain oedema are of utmost importance. Nutritional therapy in this condition has two objectives:
  • ensuring the adequate provision of required energy, especially euglycaemia, by giving glucose, lipids, vitamins and trace elements, and
  • ensuring optimal rates of protein synthesis by providing an adequate intake of protein or amino acids.
Energy intake
  • In acute liver failure a hypermetabolic state can occur. The individual energy requirement should preferably, be determined measuring energy expenditure with indirect calorimetry, or be estimated with a formula (C).
Surprisingly few liver units seem to measure, or at least calculate, the energy expenditure of patients with acute liver failure [33] despite the well-known fact that hepatic energy expenditure amounts to 25% of the overall energy expenditure [109]. A survey of 33 hepatology units in Europe showed that the resting energy expenditure was measured by 12.5% of the centres by means of indirect calorimetry, and that 53% usually used the Harris-Benedict formula; the energy requirements were not recorded in a third of centres.
In patients with acute liver failure, indirect calorimetry showed an increase in resting energy expenditure, in two studies, by 18 or 30% in comparison with healthy controls [110], [111]. Obviously, patients with acute liver failure are different from other critically ill patients regarding energy expenditure (cf. “Intensive medicine”
Substrate intake
  • Sufficient glucose administration (2–3 g/kg/d) is mandatory for prophylaxis or treatment of hypoglycaemia (C). Glucose substitutes are of no proven benefit in acute LF. Moreover, xylitol, sorbitol and fructose have to be metabolised by the liver before they can be utilized.
  • Simultaneous infusion of glucose and lipid (0.8–1.2 g/kg/d) and offers benefits regarding insulin resistance and should be used.
  • Amino acid administration is not necessary in hyper-acute LF. Amino acids (0.8–1.2 g/kg/d in PN) or protein (0.8–1.2 g/kg/d in enteral nutrition) should be used in acute or sub-acute LF in order to support protein synthesis.
In LF clinically significant hypoglycaemia [112] occure and results from a loss of hepatic gluconeogenetic capacity, lack of glycogen and hyperinsulinism [113]. It is widely accepted to treat hypoglycaemia by infusing 1.5–2 g glucose/kg body weight [114], [115]. At the end of the 1990’s, the administration of glucose doses of 6 to 10 g per kg body weight per day was practised: a blood glucose level of under 10 mmol/l was aimed for by only 39% of centres [33]. Meanwhile, the landmark study by v. d. Berghe showing that euglycaemic metabolic control improved survival has likely been helpful in setting the standard also in acute liver failure [116].
As the progress of brain oedema mainly determines the prognosis of these patients, for pathophysiological reasons, strict blood glucose control may be particularly advantageous. Increased ischemia-related damage of neurons and glia cells [117], dysfunctional leukocyte function [118] or oxidative stress have been found to be associated with hyperglycaemia. The aministration of up to 4 IU/h insulin is recommended in order to adjust blood glucose levels and maintain euglycaemia (cf. “Carbohydrates” and “Intensive medicine”
The oxidation of fatty acids and ketogenesis are the main energy-providing processes for hepatocytes [119]. Thus, adequate lipid administration would be a plausible, therapeutic objective provided there is sufficient oxygen supply to the liver tissues. Some cases of acute liver failure are, however, caused by an impairment of hepatic beta-oxidation. In these specific cases, exogenous lipid, e.g. even administering Propofol as a sedative, cannot be metabolised and can become potentially harmful [120], [121]. Measurements of substrate turnover in a study showed that there was no fatty acid absorption, but a release of free fatty acids from the splanchnic area in patients with acute liver failure in comparison to septic patients [122].
There is no systematic data on the role of lipids as a nutrient. Exogenously administered lipids seem to be well tolerated by most patients [123], [124]. A survey of hepatology centres also showed that two-thirds of the centres administer parenteral lipids in patients with acute liver failure, mainly in the form of LCT/MCT emulsions [33].
Special attention should, however, be paid when giving lipids to patients with acute liver failure and microvesicular steatosis, in whom mitochondrial dysfunction is predominant.
Monitoring should be carried out as described in the chapter on “Complications and monitoring”
Amino acids
The plasma levels of amino acids are raised 3 to 4 fold in acute liver failure. The amino acid pattern is altered, and shows a relative decrease in branched-chain amino acids and a relative increase in tryptophan, aromatic and sulphurous amino acids [125], [126], [127]. More recent data shows that the splanchnic organs cannot take up amino acids in the event of liver failure while a net uptake of amino acids can be seen in healthy humans and even in septic patients [127].
Amino acid infusion was not used as often in the past for fear of aggravating existing hyperammonaemia and hyperaminoacidaemia, and causing brain oedema and encephalopathy. In the survey of hepatology centres, more than half of the centres indicated, however, that amino acids are infused [33]. A few centres use standard amino acid solutions, while the majority use incomplete solutions with branched-chain amino acids or complete solutions enriched with branched-chain amino acids in order to correct the altered amino acid pattern and optimise the nitrogen supply [74], [128], [129].
While pathophysiological considerations provide a rationale for the use of liver-adapted solutions with an increased proportion of branched-chain amino acids, no advantage could, however, be proven in comparison to standard solutions.
An adequate metabolic monitoring is necessary in order to ensure substrate supply, which is adjusted for substrate utilisation, and to prevent substrate overload. Strict control of the plasma glucose levels (target: 5–8 mmol/L), lactate (target: 5.0 mmol/L), triglycerides (target: <3.0 mmol/L) and ammonia (target: <100 µmol/L) are necessary for this purpose.
Patients with hypophosphataemia after acetaminophen-induced liver damage have a better prognosis. Severe hypophosphataemia, however, results in respiratory insufficiency and dysfunction of the nervous system and erythrocytes [130], and thus, serum phosphate levels should be controlled stringently and corrected in order to support liver regeneration.
This article is part of the publication of the Guidelines on Parenteral Nutrition from the German Society for Nutritional Medicine (overview and corresponding address under
English version edited by Sabine Verwied-Jorky, Rashmi Mittal and Berthold Koletzko, Univ. of Munich Medical Centre, Munich, Germany.
1. Mendenhall CL, Tosch T, Weesner RE, Garcia-Pont P, Goldberg SJ, Kiernan T, Seeff LB, Sorell M, Tamburro C, Zetterman R, et al. VA cooperative study on alcoholic hepatitis. II: Prognostic significance of protein-calorie malnutrition. Am J Clin Nutr. 1986;43(2):213–218. [PubMed]
2. Mendenhall CL, Moritz TE, Roselle GA, Morgan TR, Nemchausky BA, Tamburro CH, Schiff ER, McClain CJ, Marsano LS, Allen JI, et al. A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis: results of a Department of Veterans Affairs cooperative study. Hepatology. 1993;17(4):564–576. doi: 10.1002/hep.1840170407. Available from: [PubMed] [Cross Ref]
3. Mendenhall CL, Moritz TE, Roselle GA, Morgan TR, Nemchausky BA, Tamburro CH, Schiff ER, McClain CJ, Marsano LS, Allen JI, et al. Protein energy malnutrition in severe alcoholic hepatitis: diagnosis and response to treatment. The VA Cooperative Study Group #275. JPEN J Parenter Enteral Nutr. 1995;19(4):258–265. doi: 10.1177/0148607195019004258. Available from: [PubMed] [Cross Ref]
4. Plauth M, Merli M, Kondrup J, Weimann A, Ferenci P, Müller MJ. ESPEN Consensus Group. ESPEN guidelines for nutrition in liver disease and transplantation. Clin Nutr. 1997;16(2):43–55. doi: 10.1016/S0261-5614(97)80022-2. Available from: [PubMed] [Cross Ref]
5. Achord JL. A prospective randomized clinical trial of peripheral amino acid-glucose supplementation in acute alcoholic hepatitis. Am J Gastroenterol. 1987;82(9):871–875. [PubMed]
6. Bonkovsky HL, Fiellin DA, Smith GS, Slaker DP, Simon D, Galambos JT. A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. I. Short-term effects on liver function. Am J Gastroenterol. 1991;86(9):1200–1208. [PubMed]
7. Bonkovsky HL, Singh RH, Jafri IH, Fiellin DA, Smith GS, Simon D, Cotsonis GA, Slaker DP. A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. II. Short-term effects on nitrogen metabolism, metabolic balance, and nutrition. Am J Gastroenterol. 1991;86(9):1209–1218. [PubMed]
8. Calvey H, Davis M, Williams R. Controlled trial of nutritional supplementation, with and without branched chain amino acid enrichment, in treatment of acute alcoholic hepatitis. J Hepatol. 1985;1(2):141–151. doi: 10.1016/S0168-8278(85)80762-5. Available from: [PubMed] [Cross Ref]
9. Diehl AM, Boitnott JK, Herlong HF, Potter JJ, Van Duyn MA, Chandler E, Mezey E. Effect of parenteral amino acid supplementation in alcoholic hepatitis. Hepatology. 1985;5(1):57–63. doi: 10.1002/hep.1840050114. Available from: [PubMed] [Cross Ref]
10. Mezey E, Caballería J, Mitchell MC, Parés A, Herlong HF, Rodés J. Effect of parenteral amino acid supplementation on short-term and long-term outcomes in severe alcoholic hepatitis: a randomized controlled trial. Hepatology. 1991;14(6):1090–1096. doi: 10.1002/hep.1840140624. Available from: [PubMed] [Cross Ref]
11. Nasrallah SM, Galambos JT. Aminoacid therapy of alcoholic hepatitis. Lancet. 1980;2(8207):1276–1277. doi: 10.1016/S0140-6736(80)92338-7. Available from: [PubMed] [Cross Ref]
12. Naveau S, Pelletier G, Poynard T, Attali P, Poitrine A, Buffet C, Etienne JP, Chaput JC. A randomized clinical trial of supplementary parenteral nutrition in jaundiced alcoholic cirrhotic patients. Hepatology. 1986;6(2):270–274. doi: 10.1002/hep.1840060219. Available from: [PubMed] [Cross Ref]
13. Simon D, Galambos JT. A randomized controlled study of peripheral parenteral nutrition in moderate and severe alcoholic hepatitis. J Hepatol. 1988;7(2):200–207. doi: 10.1016/S0168-8278(88)80483-5. Available from: [PubMed] [Cross Ref]
14. Swart GR, Zillikens MC, van Vuure JK, van den Berg JW. Effect of a late evening meal on nitrogen balance in patients with cirrhosis of the liver. BMJ. 1989;299(6709):1202–1203. doi: 10.1136/bmj.299.6709.1202. Available from: [PMC free article] [PubMed] [Cross Ref]
15. Verboeket-van de Venne WP, Westerterp KR, van Hoek B, Swart GR. Energy expenditure and substrate metabolism in patients with cirrhosis of the liver: effects of the pattern of food intake. Gut. 1995;36(1):110–116. doi: 10.1136/gut.36.1.110. Available from: [PMC free article] [PubMed] [Cross Ref]
16. Zillikens MC, van den Berg JW, Wattimena JL, Rietveld T, Swart GR. Nocturnal oral glucose supplementation. The effects on protein metabolism in cirrhotic patients and in healthy controls. J Hepatol. 1993;17(3):377–383. doi: 10.1016/S0168-8278(05)80221-1. Available from: [PubMed] [Cross Ref]
17. John WJ, Phillips R, Ott L, Adams LJ, McClain CJ. Resting energy expenditure in patients with alcoholic hepatitis. JPEN J Parenter Enteral Nutr. 1989;13(2):124–127. doi: 10.1177/0148607189013002124. Available from: [PubMed] [Cross Ref]
18. Österreichische Arbeitsgemeinschaft für klinische Ernährung. Empfehlungen für die parenterale und enterale Ernährungstherapie des Erwachsenen – Version 2004. Wien: AKE; 2004.
19. Alberino F, Gatta A, Amodio P, Merkel C, Di Pascoli L, Boffo G, Caregaro L. Nutrition and survival in patients with liver cirrhosis. Nutrition. 2001;17(6):445–450. doi: 10.1016/S0899-9007(01)00521-4. Available from: [PubMed] [Cross Ref]
20. Caregaro L, Alberino F, Amodio P, Merkel C, Bolognesi M, Angeli P, Gatta A. Malnutrition in alcoholic and virus-related cirrhosis. Am J Clin Nutr. 1996;63(4):602–609. [PubMed]
21. Harrison J, McKiernan J, Neuberger JM. A prospective study on the effect of recipient nutritional status on outcome in liver transplantation. Transpl Int. 1997;10(5):369–374. doi: 10.1111/j.1432-2277.1997.tb00931.x. Available from: [PubMed] [Cross Ref]
22. Merli M, Riggio O, Dally L. Does malnutrition affect survival in cirrhosis? PINC (Policentrica Italiana Nutrizione Cirrosi) Hepatology. 1996;23(5):1041–1046. doi: 10.1002/hep.510230516. Available from: [PubMed] [Cross Ref]
23. Moukarzel AA, Najm I, Vargas J, McDiarmid SV, Busuttil RW, Ament ME. Effect of nutritional status on outcome of orthotopic liver transplantation in pediatric patients. Transplant Proc. 1990;22(4):1560–1563. [PubMed]
24. Pikul J, Sharpe MD, Lowndes R, Ghent CN. Degree of preoperative malnutrition is predictive of postoperative morbidity and mortality in liver transplant recipients. Transplantation. 1994;57(3):469–472. doi: 10.1097/00007890-199402150-00030. Available from: [PubMed] [Cross Ref]
25. Selberg O, Böttcher J, Pirlich M, Henkel E, Manns M, Müller M. Clinical significance and correlates of whole body potassium status in patients with liver cirrhosis. Hepatology Res. 1999;16(1):36–48. doi: 10.1016/S1386-6346(99)00036-4. Available from: [Cross Ref]
26. Selberg O, Böttcher J, Tusch G, Pichlmayr R, Henkel E, Müller MJ. Identification of high- and low-risk patients before liver transplantation: a prospective cohort study of nutritional and metabolic parameters in 150 patients. Hepatology. 1997;25(3):652–657. doi: 10.1002/hep.510250327. Available from: [PubMed] [Cross Ref]
27. Nutritional status in cirrhosis. Italian Multicentre Cooperative Project on Nutrition in Liver Cirrhosis. J Hepatol. 1994;21(3):317–325. doi: 10.1016/S0168-8278(05)80308-3. Available from: [PubMed] [Cross Ref]
28. Lautz HU, Selberg O, Körber J, Bürger M, Müller MJ. Protein-calorie malnutrition in liver cirrhosis. Clin Investig. 1992;70(6):478–486. doi: 10.1007/BF00210228. Available from: [PubMed] [Cross Ref]
29. Bunout D, Aicardi V, Hirsch S, Petermann M, Kelly M, Silva G, Garay P, Ugarte G, Iturriaga H. Nutritional support in hospitalized patients with alcoholic liver disease. Eur J Clin Nutr. 1989;43(9):615–621. [PubMed]
30. Cabre E, Gonzalez-Huix F, Abad-Lacruz A, Esteve M, Acero D, Fernandez-Bañares F, Xiol X, Gassull MA. Effect of total enteral nutrition on the short-term outcome of severely malnourished cirrhotics. A randomized controlled trial. Gastroenterology. 1990;98(3):715–720. [PubMed]
31. Kearns PJ, Young H, Garcia G, Blaschke T, O'Hanlon G, Rinki M, Sucher K, Gregory P. Accelerated improvement of alcoholic liver disease with enteral nutrition. Gastroenterology. 1992;102(1):200–205. [PubMed]
32. Kondrup J, Müller MJ. Energy and protein requirements of patients with chronic liver disease. J Hepatol. 1997;27(1):239–247. doi: 10.1016/S0168-8278(97)80308-X. Available from: [PubMed] [Cross Ref]
33. Schütz T, Bechstein WO, Neuhaus P, Lochs H, Plauth M. Clinical practice of nutrition in acute liver failure – a European survey. Clin Nutr. 2004;23(5):975–982. doi: 10.1016/j.clnu.2004.03.005. Available from: [PubMed] [Cross Ref]
34. Keohane PP, Attrill H, Grimble G, Spiller R, Frost P, Silk DB. Enteral nutrition in malnourished patients with hepatic cirrhosis and acute encephalopathy. JPEN J Parenter Enteral Nutr. 1983;7(4):346–350. doi: 10.1177/0148607183007004346. Available from: [PubMed] [Cross Ref]
35. Garrison RN, Cryer HM, Howard DA, Polk HC., Jr Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis. Ann Surg. 1984;199(6):648–655. doi: 10.1097/00000658-198406000-00003. Available from: [PubMed] [Cross Ref]
36. Fan ST, Lo CM, Lai EC, Chu KM, Liu CL, Wong J. Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma. N Engl J Med. 1994;331(23):1547–1552. doi: 10.1056/NEJM199412083312303. Available from: [PubMed] [Cross Ref]
37. Kanematsu T, Koyanagi N, Matsumata T, Kitano S, Takenaka K, Sugimachi K. Lack of preventive effect of branched-chain amino acid solution on postoperative hepatic encephalopathy in patients with cirrhosis: a randomized, prospective trial. Surgery. 1988;104(3):482–488. [PubMed]
38. Reilly J, Mehta R, Teperman L, Cemaj S, Tzakis A, Yanaga K, Ritter P, Rezak A, Makowka L. Nutritional support after liver transplantation: a randomized prospective study. JPEN J Parenter Enteral Nutr. 1990;14(4):386–391. doi: 10.1177/0148607190014004386. Available from: [PubMed] [Cross Ref]
39. Wicks C, Somasundaram S, Bjarnason I, Menzies IS, Routley D, Potter D, Tan KC, Williams R. Comparison of enteral feeding and total parenteral nutrition after liver transplantation. Lancet. 1994;344(8926):837–840. doi: 10.1016/S0140-6736(94)92824-X. Available from: [PubMed] [Cross Ref]
40. Hasse JM, Blue LS, Liepa GU, Goldstein RM, Jennings LW, Mor E, Husberg BS, Levy MF, Gonwa TA, Klintmalm GB. Early enteral nutrition support in patients undergoing liver transplantation. JPEN J Parenter Enteral Nutr. 1995;19(6):437–443. doi: 10.1177/0148607195019006437. Available from: [PubMed] [Cross Ref]
41. Müller MJ, Lautz HU, Plogmann B, Bürger M, Körber J, Schmidt FW. Energy expenditure and substrate oxidation in patients with cirrhosis: the impact of cause, clinical staging and nutritional state. Hepatology. 1992;15(5):782–794. doi: 10.1002/hep.1840150507. Available from: [PubMed] [Cross Ref]
42. Müller MJ, Böttcher J, Selberg O, Weselmann S, Böker KH, Schwarze M, von zur Mühlen A, Manns MP. Hypermetabolism in clinically stable patients with liver cirrhosis. Am J Clin Nutr. 1999;69(6):1194–1201. [PubMed]
43. Plauth M, Schütz T, Buckendahl DP, Kreymann G, Pirlich M, Grüngreiff S, Romaniuk P, Ertl S, Weiss ML, Lochs H. Weight gain after transjugular intrahepatic portosystemic shunt is associated with improvement in body composition in malnourished patients with cirrhosis and hypermetabolism. J Hepatol. 2004;40(2):228–233. doi: 10.1016/j.jhep.2003.10.011. Available from: [PubMed] [Cross Ref]
44. Nielsen K, Kondrup J, Martinsen L, Døssing H, Larsson B, Stilling B, Jensen MG. Long-term oral refeeding of patients with cirrhosis of the liver. Br J Nutr. 1995;74(4):557–567. doi: 10.1079/BJN19950158. Available from: [PubMed] [Cross Ref]
45. Nielsen K, Martinsen L, Dossing H, Stilling B, Kondrup J. Energy expenditure measured by the doubly labeled water method during hyperalimentation of patients with liver cirrhosis. J Hepatol. 1991;13(Suppl 2):S151.
46. Campillo B, Bories PN, Devanlay M, Sommer F, Wirquin E, Fouet P. The thermogenic and metabolic effects of food in liver cirrhosis: consequences on the storage of nutrients and the hormonal counterregulatory response. Metabolism. 1992;41(5):476–482. doi: 10.1016/0026-0495(92)90204-N. Available from: [PubMed] [Cross Ref]
47. Müller MJ, Willmann O, Rieger A, Fenk A, Selberg O, Lautz HU, Bürger M, Balks HJ, von zur Mühlen A, Schmidt FW. Mechanism of insulin resistance associated with liver cirrhosis. Gastroenterology. 1992;102(6):2033–2041. [PubMed]
48. Riggio O, Merli M, Romiti A, Pinto G, Fanella R, Attili AF, Capocaccia L. Early postprandial energy expenditure and macronutrient use after a mixed meal in cirrhotic patients. JPEN J Parenter Enteral Nutr. 1992;16(5):445–450. doi: 10.1177/0148607192016005445. Available from: [PubMed] [Cross Ref]
49. Campillo B, Fouet P, Bonnet JC, Atlan G. Submaximal oxygen consumption in liver cirrhosis. Evidence of severe functional aerobic impairment. J Hepatol. 1990;10(2):163–167. doi: 10.1016/0168-8278(90)90046-T. Available from: [PubMed] [Cross Ref]
50. DeLissio M, Goodyear LJ, Fuller S, Krawitt EL, Devlin JT. Effects of treadmill exercise on fuel metabolism in hepatic cirrhosis. J Appl Physiol. 1991;70(1):210–215. [PubMed]
51. Müller MJ, Dettmer A, Tettenborn M, Radoch E, Fichter J, Wagner TO, Balks HJ, von zur Mühlen A, Selberg O. Metabolic, endocrine, haemodynamic and pulmonary responses to different types of exercise in individuals with normal or reduced liver function. Eur J Appl Physiol Occup Physiol. 1996;74(3):246–257. doi: 10.1007/BF00377447. Available from: [PubMed] [Cross Ref]
52. Plevak DJ, DiCecco SR, Wiesner RH, Porayko MK, Wahlstrom HE, Janzow DJ, Hammel KD, O'Keefe SJ. Nutritional support for liver transplantation: identifying caloric and protein requirements. Mayo Clin Proc. 1994;69(3):225–230. [PubMed]
53. Weimann A, Kuse ER, Bechstein WO, Neuberger JM, Plauth M, Pichlmayr R. Perioperative parenteral and enteral nutrition for patients undergoing orthotopic liver transplantation. Results of a questionnaire from 16 European transplant units. Transpl Int. 1998;11(Suppl 1):S289–S291. [PubMed]
54. Plank LD, Metzger DJ, McCall JL, Barclay KL, Gane EJ, Streat SJ, Munn SR, Hill GL. Sequential changes in the metabolic response to orthotopic liver transplantation during the first year after surgery. Ann Surg. 2001;234(2):245–255. doi: 10.1097/00000658-200108000-00015. Available from: [PubMed] [Cross Ref]
55. Perseghin G, Mazzaferro V, Benedini S, Pulvirenti A, Coppa J, Regalia E, Luzi L. Resting energy expenditure in diabetic and nondiabetic patients with liver cirrhosis: relation with insulin sensitivity and effect of liver transplantation and immunosuppressive therapy. Am J Clin Nutr. 2002;76(3):541–548. [PubMed]
56. Merli M, Erikson S, Hagenfeldt H, Wahren J. Splanchnic and peripheral exchange of FFA in patients with liver cirrhosis. Hepatology. 1986;3(3):348–355. doi: 10.1016/S0168-8278(86)80488-3. Available from: [PubMed] [Cross Ref]
57. Merli M, Riggio O, Romiti A, Ariosto F, Mango L, Pinto G, Savioli M, Capocaccia L. Basal energy production rate and substrate use in stable cirrhotic patients. Hepatology. 1990;12(1):106–112. doi: 10.1002/hep.1840120117. Available from: [PubMed] [Cross Ref]
58. Owen OE, Trapp VE, Reichard GA, Jr, Mozzoli MA, Moctezuma J, Paul P, Skutches CL, Boden G. Nature and quantity of fuels consumed in patients with alcoholic cirrhosis. J Clin Invest. 1983;72(5):1821–1832. doi: 10.1172/JCI111142. Available from: [PMC free article] [PubMed] [Cross Ref]
59. Petrides AS, DeFronzo RA. Glucose and insulin metabolism in cirrhosis. J Hepatol. 1989;8(1):107–114. doi: 10.1016/0168-8278(89)90169-4. Available from: [PubMed] [Cross Ref]
60. Selberg O, Burchert W, vd Hoff J, Meyer GJ, Hundeshagen H, Radoch E, Balks HJ, Müller MJ. Insulin resistance in liver cirrhosis. Positron-emission tomography scan analysis of skeletal muscle glucose metabolism. J Clin Invest. 1993;91(5):1897–1902. doi: 10.1172/JCI116407. Available from: [PMC free article] [PubMed] [Cross Ref]
61. Bianchi G, Marchesini G, Zoli M, Bugianesi E, Fabbri A, Pisi E. Prognostic significance of diabetes in patients with cirrhosis. Hepatology. 1994;20(1 Pt 1):119–125. [PubMed]
62. Müller MJ, Pirlich M, Balks HJ, Selberg O. Glucose intolerance in liver cirrhosis: role of hepatic and non-hepatic influences. Eur J Clin Chem Clin Biochem. 1994;32(10):749–758. [PubMed]
63. Wolfe RR, Allsop JR, Burke JF. Glucose metabolism in man: responses to intravenous glucose infusion. Metabolism. 1979;28(3):210–220. doi: 10.1016/0026-0495(79)90066-0. Available from: [PubMed] [Cross Ref]
64. Golling M, Lehmann T, Senninger N, Herfarth C, Otto G. Tacrolimus reduction improves glucose metabolism and insulin secretion after liver transplantation. Transplant Proc. 1996;28(6):3180–3182. [PubMed]
65. Druml W, Fischer M, Pidlich J, Lenz K. Fat elimination in chronic hepatic failure: long-chain vs medium-chain triglycerides. Am J Clin Nutr. 1995;61(4):812–817. [PubMed]
66. Müller MJ, Rieger A, Willmann O, Lautz HU, Balks HJ, Von Zur Mühlen A, Canzler H, Schmidt FW. Metabolic responses to lipid infusions in patients with liver cirrhosis. Clin Nutr. 1992;11(4):193–206. doi: 10.1016/0261-5614(92)90028-O. Available from: [PubMed] [Cross Ref]
67. Michel H, Bories P, Aubin JP, Pomier-Layrargues G, Bauret P, Bellet-Herman H. Treatment of acute hepatic encephalopathy in cirrhotics with a branched-chain amino acids enriched versus a conventional amino acids mixture. A controlled study of 70 patients. Liver. 1985;5(5):282–289. [PubMed]
68. Wahren J, Denis J, Desurmont P, Eriksson LS, Escoffier JM, Gauthier AP, Hagenfeldt L, Michel H, Opolon P, Paris JC, Veyrac M. Is intravenous administration of branched chain amino acids effective in the treatment of hepatic encephalopathy? A multicenter study. Hepatology. 1983;3(4):475–480. [PubMed]
69. Holm E, Leweling H, Saeger H, Arnold V, Gladisch R. Exogenous lipids as a caloric support in hepatic failure. In: Francavilla A, Panella C, Di Leo A, van Thiel D, editors. Liver and hormones. New York: Raven Press; 1987. pp. 125–144.
70. Naylor CD, O'Rourke K, Detsky AS, Baker JP. Parenteral nutrition with branched-chain amino acids in hepatic encephalopathy. A meta-analysis. Gastroenterology. 1989;97(4):1033–1042. [PubMed]
71. Mendenhall C, Bongiovanni G, Goldberg S, Miller B, Moore J, Rouster S, Schneider D, Tamburro C, Tosch T, Weesner R. VA Cooperative Study on Alcoholic Hepatitis. III: Changes in protein-calorie malnutrition associated with 30 days of hospitalization with and without enteral nutritional therapy. JPEN J Parenter Enteral Nutr. 1985;9(5):590–596. doi: 10.1177/0148607185009005590. Available from: [PubMed] [Cross Ref]
72. Nielsen K, Kondrup J, Martinsen L, Stilling B, Wikman B. Nutritional assessment and adequacy of dietary intake in hospitalized patients with alcoholic liver cirrhosis. Br J Nutr. 1993;69(3):665–679. doi: 10.1079/BJN19930068. Available from: [PubMed] [Cross Ref]
73. Swart GR, van den Berg JW, van Vuure JK, Rietveld T, Wattimena DL, Frenkel M. Minimum protein requirements in liver cirrhosis determined by nitrogen balance measurements at three levels of protein intake. Clin Nutr. 1989;8(6):329–336. doi: 10.1016/0261-5614(89)90008-3. Available from: [PubMed] [Cross Ref]
74. Fischer JE, Rosen HM, Ebeid AM, James JH, Keane JM, Soeters PB. The effect of normalization of plasma amino acids on hepatic encephalopathy in man. Surgery. 1976;80(1):77–91. [PubMed]
75. Freund H, Dienstag J, Lehrich J, Yoshimura N, Bradford RR, Rosen H, Atamian S, Slemmer E, Holroyde J, Fischer JE. Infusion of branched-chain enriched amino acid solution in patients with hepatic encephalopathy. Ann Surg. 1982;196(2):209–220. doi: 10.1097/00000658-198208000-00015. Available from: [PubMed] [Cross Ref]
76. Holm E, Striebel JP, Meisinger E, Haux P, Langhans W, Becker HD. Amino-acid mixtures for parenteral feeding in liver insufficiency. [Amino- säurengemische zur parenteralen Ernährung bei Leberinsuffizienz]. Infusionsther Klin Ernahr. 1978;5(5):274–292. (Ger). [PubMed]
77. Cerra FB, Cheung NK, Fischer JE, Kaplowitz N, Schiff ER, Dienstag JL, Bower RH, Mabry CD, Leevy CM, Kiernan T. Disease-specific amino acid infusion (F080) in hepatic encephalopathy: a prospective, randomized, double-blind, controlled trial. JPEN J Parenter Enteral Nutr. 1985;9(3):288–295. doi: 10.1177/0148607185009003288. Available from: [PubMed] [Cross Ref]
78. Fiaccadori F, Ginelli F, Pedretti G, Pelosi G, Sacchini D, Zeneroli M. Branched-chain enriched amino acid solutions in the treatment of hepatic encephalopathy: A controlled trial. Ital J Gastroenterol. 1985;17:5–10.
79. Rossi-Fanelli F, Riggio O, Cangiano C, Cascino A, De Conciliis D, Merli M, Stortoni M, Giunchi G. Branched-chain amino acids vs lactulose in the treatment of hepatic coma: a controlled study. Dig Dis Sci. 1982;27(10):929–935. doi: 10.1007/BF01316578. Available from: [PubMed] [Cross Ref]
80. Strauss E, Dos Santos W, Da Silva E. Treatment of hepatic encephalopathy: a randomized clinical trial comparing a branched chain enriched amino acid solution to oral neomycin. Nutr Supp Services. 1986;6:18–21.
81. Vilstrup H, Gluud C, Hardt F, Kristensen M, Køhler O, Melgaard B, Dejgaard A, Hansen BA, Krintel JJ, Schütten HJ, et al. Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy. A double-blind study of 65 patients with cirrhosis. J Hepatol. 1990;10(3):291–296. doi: 10.1016/0168-8278(90)90135-E. Available from: [PubMed] [Cross Ref]
82. Als-Nielsen B, Koretz RL, Kjaergard LL, Gluud C. Branched-chain amino acids for hepatic encephalopathy. Cochrane Database Syst Rev. 2003;(2):CD001939. doi: 10.1002/14651858.CD001939. Available from: [PubMed] [Cross Ref]
83. Plank LD, McCall JL, Gane EJ, Rafique M, Gillanders LK, McIlroy K, Munn SR. Pre- and postoperative immunonutrition in patients undergoing liver transplantation: a pilot study of safety and efficacy. Clin Nutr. 2005;24(2):288–296. doi: 10.1016/j.clnu.2004.11.007. Available from: [PubMed] [Cross Ref]
84. Singer P, Cohen J, Cynober L. Effect of nutritional state of brain-dead organ donor on transplantation. Nutrition. 2001;17(11-12):948–952. doi: 10.1016/S0899-9007(01)00671-2. Available from: [PubMed] [Cross Ref]
85. Prijatmoko D, Strauss BJ, Lambert JR, Sievert W, Stroud DB, Wahlqvist ML, Katz B, Colman J, Jones P, Korman MG. Early detection of protein depletion in alcoholic cirrhosis: role of body composition analysis. Gastroenterology. 1993;105(6):1839–1845. [PubMed]
86. Garrett-Laster M, Russell RM, Jacques PF. Impairment of taste and olfaction in patients with cirrhosis: the role of vitamin A. Hum Nutr Clin Nutr. 1984;38(3):203–214. [PubMed]
87. Weismann K, Christensen E, Dreyer V. Zinc supplementation in alcoholic cirrhosis. A double-blind clinical trial. Acta Med Scand. 1979;205(5):361–366. [PubMed]
88. Aggett P. Severe Zinc defiency. In: Mills C, editor. Zinc in Human Biology. London: Springer; 1989. pp. 259–274.
89. Barry M, Keeling PW, Feely J. Tissue zinc status and drug elimination in patients with chronic liver disease. Clin Sci (Lond) 1990;78(6):547–549. [PubMed]
90. Halsted JA, Hackley B, Rudzki C, Smith JC., Jr Plasma zinc concentration in liver diseases. Comparison with normal controls and certain other chronic diseases. Gastroenterology. 1968;54(6):1098–1105. [PubMed]
91. Thuluvath PJ, Triger DR. Selenium in chronic liver disease. J Hepatol. 1992;14(2-3):176–182. doi: 10.1016/0168-8278(92)90155-I. Available from: [PubMed] [Cross Ref]
92. Grüngreiff K, Abicht K, Kluge M, Presser HJ, Franke D, Kleine FD, Klauck S, Diete U. Clinical studies on zinc in chronic liver diseases. Z Gastroenterol. 1988;26(8):409–415. [PubMed]
93. Van der Rijt CC, Schalm SW, Schat H, Foeken K, De Jong G. Overt hepatic encephalopathy precipitated by zinc deficiency. Gastroenterology. 1991;100(4):1114–1118. [PubMed]
94. Bresci G, Parisi G, Banti S. Management of hepatic encephalopathy with oral zinc supplementation: a long-term treatment. Eur J Med. 1993;2(7):414–416. [PubMed]
95. Reding P, Duchateau J, Bataille C. Oral zinc supplementation improves hepatic encephalopathy. Results of a randomised controlled trial. Lancet. 1984;2(8401):493–495. doi: 10.1016/S0140-6736(84)92567-4. Available from: [PubMed] [Cross Ref]
96. Riggio O, Ariosto F, Merli M, Caschera M, Zullo A, Balducci G, Ziparo V, Pedretti G, Fiaccadori F, Bottari E, et al. Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy. Results of a double-blind crossover trial. Dig Dis Sci. 1991;36(9):1204–1208. doi: 10.1007/BF01307509. Available from: [PubMed] [Cross Ref]
97. Marchesini G, Fabbri A, Bianchi G, Brizi M, Zoli M. Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis. Hepatology. 1996;23(5):1084–1092. doi: 10.1002/hep.510230523. Available from: [PubMed] [Cross Ref]
98. Mills PR, Shenkin A, Anthony RS, McLelland AS, Main AN, MacSween RN, Russell RI. Assessment of nutritional status and in vivo immune responses in alcoholic liver disease. Am J Clin Nutr. 1983;38(6):849–859. [PubMed]
99. Schenker S, Halff GA. Nutritional therapy in alcoholic liver disease. Semin Liver Dis. 1993;13(2):196–209. doi: 10.1055/s-2007-1007349. Available from: [PubMed] [Cross Ref]
100. Lieber CS. Alcohol, liver, and nutrition. J Am Coll Nutr. 1991;10(6):602–632. [PubMed]
101. Lindor KD. Management of osteopenia of liver disease with special emphasis on primary biliary cirrhosis. Semin Liver Dis. 1993;13(4):367–373. doi: 10.1055/s-2007-1007365. Available from: [PubMed] [Cross Ref]
102. Crippin JS, Jorgensen RA, Dickson ER, Lindor KD. Hepatic osteodystrophy in primary biliary cirrhosis: effects of medical treatment. Am J Gastroenterol. 1994;89(1):47–50. [PubMed]
103. Lundbom N, Laurila O, Laurila S. Central pontine myelinolysis after correction of chronic hyponatraemia. Lancet. 1993;342(8865):247–248. doi: 10.1016/0140-6736(93)92343-R. Available from: [PubMed] [Cross Ref]
104. McDiarmid SV, Colonna JO, 2nd, Shaked A, Ament ME, Busuttil RW. A comparison of renal function in cyclosporine- and FK-506-treated patients after primary orthotopic liver transplantation. Transplantation. 1993;56(4):847–853. doi: 10.1097/00007890-199310000-00014. Available from: [PubMed] [Cross Ref]
105. Pomposelli JJ, Pomfret EA, Burns DL, Lally A, Sorcini A, Gordon FD, Lewis WD, Jenkins R. Life-threatening hypophosphatemia after right hepatic lobectomy for live donor adult liver transplantation. Liver Transpl. 2001;7(7):637–642. doi: 10.1053/jlts.2001.26287. Available from: [PubMed] [Cross Ref]
106. Smyrniotis V, Kostopanagiotou G, Katsarelias D, Theodoraki K, Hondros K, Kouskouni E. Changes of serum phosphorus levels in hepatic resections and implications on patients' outcomes. Int Surg. 2003;88(2):100–104. [PubMed]
107. Tan HP, Madeb R, Kovach SJ, Orloff M, Mieles L, Johnson LA, Bozorgzadeh A, Marcos A. Hypophosphatemia after 95 right-lobe living-donor hepatectomies for liver transplantation is not a significant source of morbidity. Transplantation. 2003;76(7):1085–1088. doi: 10.1097/01.TP.0000085652.47821.8A. Available from: [PubMed] [Cross Ref]
108. O'Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet. 1993;342(8866):273–275. doi: 10.1016/0140-6736(93)91818-7. Available from: [PubMed] [Cross Ref]
109. Ganong W. Review of Medical Physiology. East Norwalk: Appleton & Lange; 1991.
110. Schneeweiss B, Pammer J, Ratheiser K, Schneider B, Madl C, Kramer L, Kranz A, Ferenci P, Druml W, Grimm G, et al. Energy metabolism in acute hepatic failure. Gastroenterology. 1993;105(5):1515–1521. [PubMed]
111. Walsh TS, Wigmore SJ, Hopton P, Richardson R, Lee A. Energy expenditure in acetaminophen-induced fulminant hepatic failure. Crit Care Med. 2000;28(3):649–654. doi: 10.1097/00003246-200003000-00008. Available from: [PubMed] [Cross Ref]
112. Samson R, Trey C, Timme A, Saunders S. Fulminating hepatitis with recurrent hypoglycemia and hemorrhage. Gastroenterology. 1967;53:291–300.
113. Vilstrup H, Iversen J, Tygstrup N. Glucoregulation in acute liver failure. Eur J Clin Invest. 1986;16(3):193–197. doi: 10.1111/j.1365-2362.1986.tb01328.x. Available from: [PubMed] [Cross Ref]
114. Bernuau J, Rueff B, Benhamou JP. Fulminant and subfulminant liver failure: definitions and causes. Semin Liver Dis. 1986;6(2):97–106. doi: 10.1055/s-2008-1040593. Available from: [PubMed] [Cross Ref]
115. O'Grady JG, Portmann B, Williams R. Fulminant hepatic failure. In: Schoff L, Schiff ER, editors. Diseases of the liver. Philadelphia: Lippincott; 1993. pp. 1077–1090.
116. Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345(19):1359–1367. doi: 10.1056/NEJMoa011300. Available from: [PubMed] [Cross Ref]
117. Lin B, Ginsberg MD, Busto R. Hyperglycemic exacerbation of neuronal damage following forebrain ischemia: microglial, astrocytic and endothelial alterations. Acta Neuropathol. 1998;96(6):610–620. doi: 10.1007/s004010050942. Available from: [PubMed] [Cross Ref]
118. Delamaire M, Maugendre D, Moreno M, Le Goff MC, Allannic H, Genetet B. Impaired leucocyte functions in diabetic patients. Diabet Med. 1997;14(1):29–34. doi: 10.1002/(SICI)1096-9136(199701)14:1<29::AID-DIA300>3.0.CO;2-V. Available from:<29::AID-DIA300>3.0.CO;2-V. [PubMed] [Cross Ref]
119. Ohyanagi H, Nomura H, Nishimatsu S, Usami M, Kasahara H. The liver and nutrient metabolism. In: Payne-James J, Grimble G, Silk D, editors. Artificial nutrition and support in clinical practice. London: Edward Arnold; 1995. pp. 59–71.
120. Mahler H, Pasi A, Kramer JM, Schulte P, Scoging AC, Bär W, Krähenbühl S. Fulminant liver failure in association with the emetic toxin of Bacillus cereus. N Engl J Med. 1997;336(16):1142–1148. doi: 10.1056/NEJM199704173361604. Available from: [PubMed] [Cross Ref]
121. Schafer DF, Sorrell MF. Power failure, liver failure. N Engl J Med. 1997;336(16):1173–1174. doi: 10.1056/NEJM199704173361609. Available from: [PubMed] [Cross Ref]
122. Clemmesen JO, Høy CE, Kondrup J, Ott P. Splanchnic metabolism of fuel substrates in acute liver failure. J Hepatol. 2000;33(6):941–948. doi: 10.1016/S0168-8278(00)80126-9. Available from: [PubMed] [Cross Ref]
123. Forbes A, Wicks C, Marshall W, Johnson P, Forsey P, Williams R. Nutritional support in fulminant hepatic failure: the safety of lipid solutions. Gut. 1987;28:1347–1349.
124. Kleinberger G. Parenteral nutrition in liver insufficiency. [Parenterale Ernährung bei Leberinsuffizienz]. Schweiz Med Wochenschr. 1986;116(17):545–549. (Ger). [PubMed]
125. Clemmesen JO, Kondrup J, Ott P. Splanchnic and leg exchange of amino acids and ammonia in acute liver failure. Gastroenterology. 2000;118(6):1131–1139. doi: 10.1016/S0016-5085(00)70366-0. Available from: [PubMed] [Cross Ref]
126. Record CO, Buxton B, Chase RA, Curzon G, Murray-Lyon IM, Williams R. Plasma and brain amino acids in fulminant hepatic failure and their relationship to hepatic encephalopathy. Eur J Clin Invest. 1976;6(5):387–394. doi: 10.1111/j.1365-2362.1976.tb00533.x. Available from: [PubMed] [Cross Ref]
127. Rosen HM, Yoshimura N, Hodgman JM, Fischer JE. Plasma amino acid patterns in hepatic encephalopathy of differing etiology. Gastroenterology. 1977;72(3):483–487. [PubMed]
128. Frydén A, Weiland O, Mårtensson J. Successful treatment of hepatic coma probably caused by acute infectious hepatitis with balanced solution of amino acids. Scand J Infect Dis. 1982;14(3):177–180. [PubMed]
129. Hensle T, Blackburn GL, O'Donnell T, McDermott WV., Jr Intravenous feeding in hepatic failure. Surg Forum. 1973;24:388–391. [PubMed]
130. Schmidt LE, Dalhoff K. Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity. Hepatology. 2002;36(3):659–665. doi: 10.1053/jhep.2002.35069. Available from: [PubMed] [Cross Ref]
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