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S45
Nutritional support in the treatment of chronic hepatic encephalopathy. , 2011; 10 (Suppl.2): S45-S49
MODULE ?
Vol. 10 Suppl.2, 2011: S45-S49
Nutritional support in the
treatment of chronic hepatic encephalopathy
María del Pilar Milke García*
* Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. México, D.F., México.
ABSTRACT
The prevalence of under nutrition in cirrhotic patients is 61% and it usually progresses as the disease
becomes more advanced. The deterioration in the nutritional status and its associated metabolic derange-
ments has raised doubts about the benefits of severe and prolonged protein restriction as a treatment for
hepatic encephalopathy. However, the practice of dietary protein restriction for patients with liver
cirrhosis is deeply embedded among medical practitioners and dietitians. To date, no solid conclusions
may be drawn about the benefit of protein restriction. However, the negative effects of protein restric-
tion are clear, that is, increased protein catabolism, the release of amino acids from the muscle, and pos-
sible worsening of hepatic encephalopathy. In conclusion, chronic protein restriction causes progressive
and harmful protein depletion and must be avoided.
Key words. Nutrition. Hepatic encephalopathy. Protein metabolism. Protein restriction. Protein supplementation.
INTRODUCTION comes more advanced,2 reflecting the severity of the
disease. A prospective study on a large series of
Among the multiple functions of the liver, protein cirrhotic patients showed that severe malnutrition
metabolism is a mainstay for life support, as the li- –including depletion of lean body mass– is an inde-
ver synthesizes most of the body proteins from ami- pendent prognostic factor for the survival of pa-
no acids absorbed from the digestive tract. Protein tients with liver cirrhosis.3
degradation is also important, as it generates free Liver cirrhosis increases nutritional require-
amino acids, which may be transaminated or deami- ments and clearly increases morbidity and mortali-
nated, producing ammonia. This toxic metabolite is ty. Undernutrition may be explained by metabolic
effectively removed from the circulation by hepatic derangements that accompany liver damage and by
conversion to urea, which is then eliminated in the hypermetabolism, hypercatabolism, malabsorption
urine by the kidney. However, when liver function and decreased ingestion because of anorexia, early
is impaired, hyperammonemia ensues, increasing satiety and nausea/vomiting. The lack of accurate
the likelihood of developing hepatic encephalopathy. data on the effect of nutrition on the outcome of li-
Undernutrition –particularly protein-calorie mal- ver disease and on the possible benefits of not res-
nutrition– is highly prevalent in patients with liver tricting dietary protein intake (vide infra) may
cirrhosis; nevertheless, its occurrence varies widely, aggravate protein-calorie undernutrition in these
depending on the selection of nutritional assessment patients.
parameters. A recent study estimated that the preva-
1
lence of undernutrition in cirrhotic patients is 61%, GENERAL ASPECTS
and although it may not be related to the cause of
liver disease, it usually progresses as the disease be- Pathophysiology of hepatic encephalopathy is yet
the matter of discussion, and several theories have
been proposed. Among them, the ammonia theory is
Correspondence and reprint request: María del Pilar Milke García, PhD. 4
Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” most widely spread and best supported; other
E-mail: nutriclinica@hotmail.com theories implicate the ratio of branched-chain amino
Manuscript received: May 5, 2010. acids (BCAAs: Ile, Leu, Val) vs. aromatic amino acids
Manuscript accepted: May 6, 2010. (AAA; Phe, Tyr, Try), GABA, false neurotransmit-
S46
Milke GMP. , 2011; 10 (Suppl.2): S45-S49
15
ters, serotonin, mercaptans, phenols, short-chain progressive and harmful protein depletion, must be
fatty acids and, most recently, manganese. avoided.16-19
Ammonia may originate from dietary proteins or Protein restriction was first proposed on a theo-
20-22
the activity of intestinal urease or intestinal or retical basis and according to anecdotal cases,
renal glutaminase. Surprisingly, nearly 85% of total but as recently as 1989, Sherlock recommended as
23
blood ammonia may be generated by intestinal glu- little as 20 g of protein per day as a therapy for he-
tamine deamination, whereas as little as 10-15% patic encephalopathy. However, since these reports
may originate from the deamination of proteins by were published, the only randomized study conduc-
the gut macrobiota.5 Ammonia is undoubtedly toxic, ted found no difference in the development of hepa-
and must be removed from the bloodstream by hepa- tic encephalopathy between a protein-restricted diet
19
tic conversion to urea and elimination of urea by the and a normal diet. Although several meta-analyses
kidney, or even as nonconverted ammonia in urine. have been performed, no solid conclusions could be
The importance of muscle glutamine formation as a drawn about the benefit of protein restriction becau-
means of removing ammonia from the bloodstream se of great variation in study design and the consi-
has also been stressed recently, implying that skele- derable number of confounding factors that were
tal muscle plays a crucial role in ammonia detoxifi- not properly controlled for in the studies. However,
cation. However, the role of muscle glutamine the negative effects of protein restriction are clear,
formation in ammonia detoxification is mitigated to that is, increased protein degradation and possible
an extent by the reconversion of glutamine to gluta- worsening of hepatic encephalopathy,6 worsening of
mic acid and ammonia in the gut.6 Nonetheless, the nutritional status and increased mortality because
liver and muscle play central roles in ammonia de- of alcoholic liver disease. Therefore, dietary protein
toxification by converting it to urea (liver) and glu- restriction cannot be recommended at present. No-
5
tamine (liver and muscle). netheless, the practice of dietary protein restriction
Insulin resistance is a frequent finding in advan- for patients with liver cirrhosis is so deeply em-
7 15
ced liver disease. The inability of the diseased liver bedded among medical practitioners and dietitians
to produce glucose via glycogenolysis increases the that it may be years before it is abandoned.
utilization of alanine and glycerol, causing catabo- Patients with liver disease may differ in their tole-
lism of muscle and adipose tissue, respectively. Whe- rance to protein, depending on the dietary amino
reas the BCAA-to-AAA ratio is 3:1 or 4:1 in healthy acid profile and fiber content. Vegetable proteins are
individuals, patients with liver cirrhosis exhibit a ra- thought to be best tolerated, followed by proteins
8
tio of 1:1, possibly because muscle stores BCAAs or contained in dairy foods –mainly milk– which may
because BCAAs are used by the kidneys as substrates also contain lactose, a disaccharide that exerts a si-
9
for gluconeogenesis during insulin resistance. milar effect in lactose-intolerant people to that exer-
During the past decade, elucidation of the progre- ted by other nonabsorbable disaccharides used in
ssive deterioration in the nutritional status of pa- the treatment of hepatic encephalopathy, such as
tients with liver cirrhosis and its associated lactulose and lactitol.
metabolic derangements has raised doubts about the Vegetables are thought to be beneficial not only be-
benefits of severe and prolonged protein restriction cause of their high content of fiber, which promotes
10
as a treatment for hepatic encephalopathy because bacterial fermentation and decreases colonic transit
11
of a lack of scientific proof. Swart, et al. showed time, decreasing ammonia absorption from the gut,
that a protein-restricted diet supplying 40 g of pro- but also because of their high BCAA content, low Met
tein per day was unable to achieve positive nitrogen and Try contents, and the induction of gut microbio-
balance in cirrhotic patients and suggested that the ta which, in turn, increases fecal nitrogen excre-
12 15
protein requirement of these patients is elevated. tion. The effectiveness of a vegetarian diet was
Studies on malnourished cirrhotic patients reported proven by Bianchi24 and Uribe;25 however, no positive
26 27
that they retained nitrogen upon repletion feeding at effects were shown by Shaw or Chiarino. Never-
a rate greater than that considered normal, similar theless, also supporting the underlying rationale for
to that observed with repletion feeding of un- the use of vegetable proteins is the fact that dietary
13
derweight, healthy individuals, and that protein fiber contributes to the improvement of glycemic con-
repletion feeding induces a significant increase trol in these patients.28 However, as a diet containing
14
in protein synthesis. Therefore, chronic protein more than 40% vegetable protein causes bloating, fla-
restriction, which increases protein catabolism and tulence and early satiety, vegetarian diets are fre-
the release of amino acids from the muscle, causing quently poorly tolerated in the long term. To obtain a
S47
Nutritional support in the treatment of chronic hepatic encephalopathy. , 2011; 10 (Suppl.2): S45-S49
more palatable and varied dietary regimen, dairy are exceptions, and should be deprived of protein32
foods may be added; this high-protein diet is well tole- (Table 1).
rated and has proven to be beneficial in patients with The above evidence negates the longstanding be-
cirrhosis and hepatic encephalopathy.29 lief that protein intake can easily result in deterio-
The primary goal of the treatment of hepatic en- ration of hepatic encephalopathy. Rather, in a
cephalopathy is a reduction in blood ammonia level, double-blind randomized trial to compare oxandrolo-
which can be achieved by supplementation with ne and Hepatic Aid II® (BCAA) with a placebo in
AACR, ketoanalogues, L-ornithine L-aspartate (or patients with alcoholic hepatitis, Morgan demons-
its ketoanalogues) or zinc (an important coenzyme trated that a high protein intake improved mental
in the urea cycle). In 1973, Rudman measured the status and that a decrease in protein intake was as-
ammonia content of several food items and proposed sociated with deterioration in mental status.34
that the avoidance of food with high ammonia con- This study was the basis for an elegant, well-desig-
tent (blood, gelatin, brewer’s yeast, bacon) could re- ned study conducted by Córdoba19 that showed that
duce the risk of encephalopathy.30 a very low-protein diet increased protein breakdown
In 1997, the European Society of Parenteral and and did not have any major benefit in hepatic ence-
Enteral Nutrition (ESPEN) published a consensus phalopathy patients. These results support the
on specific guidelines for nutrition in liver disease hypothesis that long-term protein restriction may
31 35
and transplantation. These guidelines increased worsen the patient’s nutritional status.
the protein requirements of cirrhotic patients and The use of BCAAs, mainly as intravenous solu-
recommended a diet containing at least 1.2 g of pro- tions, for the treatment of hepatic encephalopathy
tein per kg body weight per day. Interestingly, they was established almost 25 years ago. Although a
also state that hepatic encephalopathy should not be meta-analysis by Naylor suggested that there might
a reason to limit the protein content of the diet to 1- be a trend in favor of a beneficial effect of BCAAs,
1.5 g of protein per kg body weight per day unless the conclusions of this study are debatable because
the protein restriction is very transient and is of differences in study designs, small numbers of pa-
36
applied in conjunction with BCAA-enriched amino tients and short observation periods. A Cochrane
acid solutions. Patients with liver disease should re- review then showed that patients supplemented with
ceive sufficient energy (35-40 Kcal/kg/d) to prevent BCAAs (either intravenous or oral) were more likely
the degradation of endogenous protein to provide to recover from hepatic encephalopathy than pa-
energy, and up to 1.6 of protein per kg body weight tients who received a standard solution and lactulo-
31,32 37
per day should be supplied. For patients with se or neomycin; however, survival was not affected
compensated liver cirrhosis, this goal can be achie- by BCAAs. Finally, a meta-analysis by Marchesini38
ved with a normal diet without restricting its carbo- demonstrated that BCAAs may reduce hospital ad-
hydrate, protein or fat content. In cases of missions and the duration of hospital stay, and a
uncompensated cirrhosis, supplementary BCAAs are meta-analysis by Muto39 showed that BCAAs signifi-
often recommended and prescribed.33 According to cantly improved a composite end-point and tended to
31
the ESPEN consensus report of 2006, low-grade reduce hepatic encephalopathy. Nonetheless, it is
hepatic encephalopathy (grades I and II) is not re- noteworthy that noncompliance with or rejection of
garded as a reason for dietary or protein restriction, BCAAs is a problem of palatability.15
indicating that malnutrition is certainly considered Cirrhotic patients exhibit an early onset of gluco-
40
a negative prognostic factor. However, patients with neogenesis after short-term fasting. This accelera-
severe hepatic encephalopathy (grades III and IV) ted metabolic reaction to starvation may underlie
Table 1. Clinical condition and intake.16
Clinical condition Non protein energy Protein or amino acids
(kcal/g/day) (g/kg/day)
Compensated cirrhosis 25-35 1.0-1.2
Complications Inadequate intake Malnutrition 35-40 1.5
Low-grade encephalopathy 25-35 Transient 1.0-1.5; if protein intolerant,
vegetable protein or BCAA supplement
High-grade encephalopathy 25-35 0.5-1.0, BCAA-enriched amino-acid solution
S48
Milke GMP. , 2011; 10 (Suppl.2): S45-S49
their increased protein requirements and muscle de- 5. Duarte RA, Estradas TJ, Torre A, Uribe M. Avances en la fi-
pletion. A late evening snack (especially one that siopatología de la encefalopatía hepática. Medicas Dis
contains a BCAA mixture) improves the catabolic 2007; 20: 195-202.
33 6. Olde DSWM, Jalan R, Redhead DN, Hayes PC, Deutz NEP,
state of patients with advanced liver cirrhosis. Soeters PB. Interorgan ammonia and amino acid metabo-
Yamauchi showed that this nocturnal supplement lism in metabolically stable patients with cirrhosis and a
decreases the rate of 3-methylhistidine production TIPSS. Hepatology 2002; 37: 1163-70.
by muscle and free fatty acid formation (reflective 7. Merli M, Erikson SSL, Hagenfeldt H, Wahren J. Splanchnic
and peripheral exchange of FFA in patients with liver cirr-
of muscle and adipose tissue degradation, respectively) hosis. J Hepatol 1986; 3: 348-5.
41 8. Fischer JE, Yoshimura N, Aguirre A, James JH, Cummings
and increases albumin production. MG, Abel RM, Deindoerfer F. Plasma amino acids in pa-
Although the uptake of BCAA supplementation tients with hepatic encephalopathy. Effects of amino acid
may be limited by noncompliance and its costs, there infusions. Am J Surg 1974; 127: 40-7.
is increasing evidence that these amino acids may 9. Soeters PB, Fischer JE. Insulin, glucagon and amino acid
assist intolerant patients to achieve the protein imbalance and hepatic encephalopathy. Lancet 1976; 2:
requirement and prevent endogenous protein 880-2.
breakdown; thus, it is a valuable tool in the manage- 10. Mullen KD, Dasarathy S. Protein restriction in hepatic en-
15 cephalopathy: necessary evil or illogical dogma? J Hepatol
ment of advanced liver disease. 2004; 41: 147-8.
11. Plauth M, Merli M, Kondrup J. Management of hepatic en-
CONCLUSION cephalopathy. N Eng J Med 1997; 337: 1921-2.
12. Swart GR, Van den Berg JWO, Wattimena JLD, Rietveld T,
Van Vuure JK, Frenkel M. Elevated protein requirements
Severe malnutrition is an independent prognos- in cirrhosis of the liver investigated by whole body pro-
tic factor for the survival of patients with cirrho- tein turnover studies. Clin Sci 1988; 75: 101-7.
sis. A low protein diet increased protein breakdown 13. Nielsen K, Kondrup J, Martinsen L, Dossing H, Larsson B,
and did not have any major benefit in hepatic ence- Stilling B, Jensen MG. Long-term oral refeeding of patients
with cirrhosis of the liver. Br J Nutr 1995; 74: 557-67.
phalopathy patients. Vegetable proteins are the 14. Kondrup J, Nielsen K, Juul A. Effect of long-term refeeding
best tolerated, followed by proteins contained in on protein metabolism in patients with cirrhosis of the li-
dairy foods. The protein requirements of compen- ver. Br J Nutr 1997; 77: 197-211.
sated cirrhotic patients consist on a diet contai- 15.Merli M, Riggio O. Dietary and nutritional indications in
hepatic encephalopathy. Metab Brain Dis 2009; 24:
ning at least 1.2 g of protein per kg body weight 211-21.
per day. Hepatic encephalopathy should not be a 16. Plauth M, Merli M, Kondrup J, Weimann A, Ferenti P, Muller
reason to limit the protein content of the diet, and MJ. ESPEN guidelines for nutrition in liver disease and
the requirements are 1-1.5 g of protein per kg body transplantation. Clin Nutr 1997; 16: 43-5.
17. Mizock BA. Nutritional support in hepatic encephalopathy.
weight per day. Patients with severe hepatic ence- Nutrition 1999; 15: 220-8.
phalopathy (grades III and IV) are exceptions; they 18. Blei AT, Córdoba J. Hepatic encephalopathy. Am J Gas-
may probably benefit of transient protein restric- troenterol 2001; 96: 1968-75.
tion and should receive 0.5-1 g per kg body weight 19. Córdoba J, López-Hellin J, Planas M, Sabin P, Sanpedro F,
Castro F, et al. Normal protein diet for episodic hepatic
per day in conjunction with BCAA-enriched amino encephalopathy: results of a randomized study. J Hepatol
acid solutions. In conclusion, protein restriction in 2004; 41: 38-43.
patients with cirrhosis worsens nutritional status 20. Hahn M, Massen O, Nencki M. Die Eck’s Fistel zwischen der
and hepatic encephalopathy and therefore should unteren Holvene und der Pfortader und ihre Folgen fur
den Organismus. Arch Exper Patol Pharmakol 1883; 13:
be avoided. 161–210.
21. Balo J, Korpassy B. The encephalitis of the dog with Eck
REFERENCES fistula fed on meat. Arch Pathol 1932; 13: 80-7.
22. Sherlock S, Summerskill WHJ, White LP, Phear EA. Portal-
1. Guex E, Cheseaux M, Bertrand PC, Piquet MA, Bouvry S, systemic encephalopathy. Neurological complications of li-
Pilon N, et al. Prevalence of undernutrition in 143 patients ver disease. Lancet 1954; 267: 454-7.
before liver transplantation. The Lausanne experience 23.Sherlock S. Hepatic encephalopathy. In: Diseases of the
between 1997 and 2005. Rev Med Suisse 2008; 4: 927-30. liver and biliary system. Oxford, UK: Blackwell; 1989: p.
2. Italian Multicentre Cooperative Project on Nutrition in Li- 109-10.
ver Cirrhosis. Nutritional status in cirrhosis. J Hepatol 24. Bianchi GP, Marchesini G, Fabbri A, Rondelli A, Bugianesi E,
1994; 21: 317-25. Zoli M, Pisi E. Vegetable versus animal protein diet in cirr-
3. Merli M, Riggio O, Dally L. Policentrica Italiana Nutrizione hotic patients with chronic encephalopathy. A randomized
Cirrosi. Does malnutrition affect survival in cirrhosis? He- cross-over comparison. J Intern Med 1993; 233: 385-92.
patology 1995; 24: 1041-6. 25. Uribe M, Márquez MA, García RG, Ramos UMH, Vargas F,
4. Zeman FJ. Liver disease and alcoholism. In: Zeman FJ Villalobos A. Treatment of chronic portal-systemic ence-
(ed.). Clinical nutrition and dietetics. NY, USA: Macmillan; phalopathy with vegetable and animal protein diets. A con-
1991, p. 517-53. trolled crossover study. Dig Dis Sci 1982; 27: 1109–16.
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