Protein calorie malnutrition (PCM) is a well-known complication of chronic liver disease (CLD). A major contribution to PCM in CLD is restriction of dietary protein intake. After many decades of injudicious reduction in dietary protein, cirrhotic patients are now prescribed appropriate amounts of protein. PCM in CLD is known to be associated with life-threatening complications. In the general approach to these patients, the initial and most important step for the clinician is to recognize the extent of malnutrition. Most patients tolerate a normal amount of dietary protein without developing hepatic encephalopathy (HE). Oral branched-chain amino acids (BCAAs) have a limited role in HE. Patients who exhibit dietary protein intolerance originally were thought to be best treated with BCAA formulations. Mixed evidence has been reported in multiple studies. In keeping with other reports, this article shows that in animal protein–intolerant patients, even those with advanced cirrhosis, vegetable protein–based diets are well tolerated. Another approach to management of apparent dietary intolerance is to optimize HE treatment with available medications. This article reviews the causes of HE, minimal HE, and PCM; examines nutrition requirements and assessment; and discusses treatment options for malnutrition in HE.
O’BrienAWilliamsR. Nutrition in end-stage liver disease: principles and practice. Gastroenterology. 2008;134:1729-1740.
2.
KalaitzakisEBjornssonE. Hepatic encephalopathy in patients with liver cirrhosis: is there a role of malnutrition. World J Gastroenterol. 2008;14:3438-3439.
3.
SeymourCAWhelanK. Dietary management of hepatic encephalopathy: too many myths persist. BMJ. 1999;318:1364-1365.
4.
NompleggiDJBonkovskyHL. Nutritional supplementation in chronic liver disease: an analytical review. Hepatology. 1994;19:518-533.
5.
CharltonM. Branched-chain amino acid supplements as therapy for liver disease. J Nutr. 2006;136:295S-298S.
6.
ShawcrossDJalanR. The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. Cell Mol Life Sci. 2005;62:2295-2304.
7.
ShawcrossDJalanR. Dispelling myths in the treatment of hepatic encephalopathy. Lancet. 2005;365:431-433.
8.
PanickarKSJayakumarARRaoKVNorenbergMD. Ammonia-induced activation of p53 in cultured astrocytes: role in cell swelling and glutamate uptake. Neurochem Int. 2009;55:98-105.
9.
BajajJSSaeianKChristensenKM. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am J Gastroenterol. 2008;103:1707-1715.
10.
BajajJSHafeezullahMFrancoJ. Inhibitory control test for the diagnosis of minimal hepatic encephalopathy. Gastroenterology. 2008;135:1591-1600.
11.
DhimanRKChawlaYK. Minimal hepatic encephalopathy: time to recognize and treat. Trop Gastroenterol. 2008;29:6-12.
12.
MerliMRiggioO. Dietary and nutritional indications in hepatic encephalopathy. Metab Brain Dis. 2009;24:211-221.
13.
GabuzdaGJShearL. Metabolism of dietary protein in hepatic cirrhosis: nutritional and clinical considerations. Am J Clin Nutr. 1970;23:479-487.
14.
PhillipsGBSchwartzRGabuzdaGJJrDavidsonCS. The syndrome of impending hepatic coma in patients with cirrhosis of the liver given certain nitrogenous substances. N Engl J Med. 1952;247:239-236.
15.
GheorgheLIacobRVadanRGheorgheC. Improvement of hepatic encephalopathy using a modified high-calorie high-protein diet. Rom J Gastroenterol. 2005;14:231-238.
16.
CardobaJLopez-HellinJPlanasM. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41:38-43.
17.
MullenKDDasarathyS. Protein restriction in hepatic encephalopathy necessary evil or illogical dogma?J Hepatol. 2004;41:147-148.
18.
WolfeRRMillerSL. The recommended dietary allowance of protein: a misunderstood concept. JAMA. 2008;299:2891-2893.
19.
HeymanJKWhitfieldCJBrockKE. Dietary protein intakes in patients with hepatic encephalopathy and cirrhosis: current practice in NSW and ACT. MJA. 2006;185:542-543.
20.
PlauthMMerliMKondrupJ; ESPEN Consensus Group. ESPEN guidelines for nutrition in liver disease and transplantation. Clin Nutr. 1997;16:43-55.
21.
McCulloughAJMullenKDSmanikEJTabbaaMSzauterK. Nutrition therapy and liver disease. Gastroenterol Clin North Am. 1989;18:619-641.
22.
KrenitskyJ. Nutrition for patients with hepatic failure. Practical Gastroenterol. 2003;6:23-42.
23.
CarvalhaLPariseER. Evaluation of nutritional status of non hospitalized patients with liver cirrhosis. Arq Gastroenterol. 2006;43:269-274.
24.
SelbergOBottcherJTuschGPichlmayrRHenkelEMüllerMJ. Identification of high and low-risk patients before liver transplantation: a prospective cohort study of nutritional and metabolic parameters in 150 patients. Hepatology. 1997;25:652-657.
25.
MorganTRMendenhallCL. Nutritional therapy for alcoholic hepatitis: are we there yet. Hepatology. 1992;16:845-848.
26.
SchulzGJCamposACCoelhoJC. The role of nutrition in hepatic encephalopathy. Curr Opin Clin Nutr Metab Care. 2008;11:275-280.
27.
SrivastavaNSinghNJoshiYK. Nutrition in the management of hepatic encephalopathy. Trop Gastroenterol. 2003;24:59-62.
28.
WahrenJDenisJDesurmontP. Is intravenous administration of branched chain amino acids effective in the treatment of hepatic encephalopathy? A multicenter study. Hepatology. 1983;3:475-480.
29.
MerliMRiggioO. Dietary and nutritional indications in hepatic encephalopathy. Metab Brain Dis. 2009;24:211-221.
30.
Olde DaminkSWJalanRDeutzNE. The kidney plays a major role in the hyperammonemia seen after simulated or actual GI bleeding in patients with cirrhosis. Hepatology. 2003;37:1277-1285.
31.
DudrickSJKavicSM. Hepatobiliary nutrition: history and future. J Hepatobiliary Pancreat Surg. 2002;9:459-68.
32.
BlackburnGLBistrianBRMainiBSSchlammHTSmithMF. Nutritional and metabolic assessment of the hospitalized patient. JPEN J Parenter Enteral Nutr. 1977;1:11-22.
33.
MendenhallCLToschTWeesnerRE. VA cooperative study on alcoholic hepatitis, II: prognostic significance of protein-calorie malnutrition. Am J Clin Nutr. 1986;43:213-218.
34.
PirlichMSelbergOBokerKSchwarzeMMüllerMJ. The creatinine approach to estimate skeletal muscle mass in patients with cirrhosis. Hepatology. 1996;24:1422-1427.
35.
PengSPlankLDMcCallJLGillandersLKMcIlroyKGaneEJ. Body composition, muscle function, and energy expenditure in patients with liver cirrhosis: a comprehensive study. Am J Clin Nutr. 2007;85:1257-1266.
36.
KondrupJJohansenNPlumLM. Incidence of nutritional risk and causes of inadequate nutritional care in hospitals. Clin Nutr. 2002;21:461-468.
37.
BianchiGPMarchesiniGZoliM. Oral BCAA supplementation in cirrhosis with chronic encephalopathy: effects on prolactin and estradiol levels. Hepatogastroenterology. 1992;39:443-446.
38.
BianchiGPMarchesiniGFabbriA. Vegetable versus animal protein diet in cirrhotic patients with chronic encephalopathy: a randomized cross-over comparison. J Intern Med. 1993;233:385-392.
39.
PlauthMRoskeAERomaniukP. Post-feeding hyperammonemia with transjugular intrahepatic portosystemic shunt and liver cirrhosis: role of small intestinal ammonia release and route of nutrient administration. Gut. 2000;46:849-855.
40.
van BerloCLHvan LeeuwenPAMSoetersPB. Porcine intestinal ammonia liberation. Influence of food intake, lactulose and neomycin treatment. J Hepatol. 1988;7:250-257.
41.
SugarbakerSPRevhaugAWilmoreDW. The role of the small intestine in ammonia production after gastric blood administration. Ann Surg. 1987;206:5-17.
42.
PlauthMRaibleAGraserTA. Lactulose or paromomycin do not affect ammonia generation in the isolated perfused rat small intestine. Z Gastroenterol. 1994;32:141-145.
43.
SwartGRZillikensMCvan VuureJK. Effect of a late evening meal on nitrogen balance in patients with cirrhosis of the liver. Br Med J. 1989;299:1202-1203.
44.
PlankLDGaneEJPengS. Nocturnal nutritional supplementation improves total body protein status of patients with liver cirrhosis: a randomized 12-month trial. Hepatology. 2008;48:557-566.
KeshavarzianAMeekJSuttonCEmeryVMHughesEAHodgsonHJ. Dietary protein supplementation from vegetable sources in the management of chronic portal systemic encephalopathy. Am J Gastroenterol. 1984;79:945-949.
47.
UribeMDibildoxMMalpicaS. Beneficial effect of vegetable protein diet supplemented with psyllium plantago in patients with hepatic encephalopathy and diabetes mellitus. Gastroenterology. 1985;88:901-907.
48.
PlauthMCabreECampilloB. ESPEN guidelines on parenteral nutrition: hepatology. Clin Nutr. 2009;28:436-444.
49.
WeberFLJrBagbyBSLicateLKelsenSG. Effects of branched-chain amino acids on nitrogen metabolism in patients with cirrhosis. Hepatology. 1990;11:942-950.
50.
MarchesiniGMarzocchiRNoiaMBianchiG. Branched-chain amino acid supplementation in patients with liver diseases. J Nutr. 2005;135(6 suppl):1596S-1601S.
51.
BieniaRRatcliffSBarbourGLKummerM. Malnutrition and hospital prognosis in the alcoholic patient. JPEN J Parenter Enteral Nutr. 1982;6:301-303.
52.
BlendisLMHarrisonJERussellDM. Effects of peritoneovenous shunting on body composition. Gastroenterology. 1986;90:127-134.
53.
NakayaYHaradaNKakuiS. Severe catabolic state after prolonged fasting in cirrhotic patients: effect of oral branched-chain amino-acid-enriched nutrient mixture. J Gastroenterol. 2002;37:531-536.
54.
MarchesiniGDioguardiFSBianchiGP. Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy: a randomized double-blind casein-controlled trial. The Italian Multicenter Study Group. J Hepatol. 1990;11:92-101.
55.
MutoYSatoSWatanabeA; Long-Term Survival Study Group. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol. 2005;3:705-713.
56.
HorstDGraceNDConnHO. Comparison of dietary protein with an oral, branched chain-enriched amino acid supplement in chronic portal-systemic encephalopathy: a randomized controlled trial. Hepatology. 1984;4:279-287.
57.
MoriwakiHShirakiMFukushimaH. Long-term outcome of branched-chain amino acid treatment in patients with liver cirrhosis. Hepatol Res. 2008;38(suppl I):S102-S106.
58.
MerliMRiggioO. Dietary and nutritional indications in hepatic encephalopathy. Metab Brain Dis. 2009;24:211-221.
59.
OhashiHSukegawaETakamiTYoshidaTMutoY. Effects of supplementation with branched-chain amino acids on protein-nutritional status in rats treated by carbon tetrachloride. Nippon Shokakibyo Gakkai Zasshi. 1989;86:1645-1653.
60.
WatanabeAWakabayashiHKuwabaraY. Nutrient-induced thermogenesis and protein-sparing effect by rapid infusion of a branched chain-enriched amino acid solution to cirrhotic patients. J Med. 1996;27:176-182.
61.
VilstrupHGluudCHardtF. Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy: a double-blind study of 65 patients with cirrhosis. J Hepatol. 1990;10:291-296.
62.
WatanabeAShiotaTOkitaMNagashimaH. Effect of a branched chain amino acid-enriched nutritional product on the pathophysiology of the liver and nutritional state of patients with liver cirrhosis. Acta Med Okayama. 1983;37:321-333.
63.
PlauthMEgbertsEHHamsterW. Long-term treatment of latent portosystemic encephalopathy with branched-chain amino acids: a double-blind placebo-controlled crossover study. J Hepatol. 1993;17:308-314.
64.
EgbertsEHSchomerusHHamsterWJurgensP. Branched chain amino acids in the treatment of latent portosystemic encephalopathy: a double-blind placebo-controlled crossover study. Gastroenterology. 1985;88:887-895.
65.
CerraFBMcMillenMAngelicoR. Cirrhosis, encephalopathy, and improved results with metabolic support. Surgery. 1983;94:612-619.
66.
SiegAWalkerSCzyganP. Branched-chain amino acid-enriched elemental diet in patients with cirrhosis of the liver: a double blind crossover trial. Z Gastroenterol. 1983;21:644-650.
67.
MichelHBoriesPAubinJP. 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;5:282-289.
68.
McGheeAHendersonJMMillikanWJJr. Comparison of the effects of hepatic-aid and a casein modular diet on encephalopathy, plasma amino acids, and nitrogen balance in cirrhotic patients. Ann Surg. 1983;197:288-293.
69.
MaddenAMBradburyWMorganMY. Taste perception in cirrhosis: its relationship to circulating micronutrients and food preferences. Hepatology. 1997;26:40-48.
70.
RabbaniPPrasadAS. Plasma ammonia and liver ornithine transcarbamoylase activity in zinc-deficient rats. Am J Physiol. 1978;235:E203-E206.
71.
MarchesiniGFabbriABianchiGBriziMZoliM. Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis. Hepatology. 1996;23:1084-1092.
