Branched-chain amino acids for people with hepatic encephalopathy

Cochrane Database of Systematic Reviews

Volumn 2017, Issue 5, 2017, Pages

  Gluud, Lise Lotte ^a   Dam, Gitte ^b   Les, Iñigo ^c   Marchesini, Giulio ^d   Borre, Mette ^b   Aagaard, Niels Kristian ^b   Vilstrup, Hendrik ^b  

^a HVIDOVRE HOSPITAL   (Denmark)

^b AARHUS UNIVERSITY HOSPITAL   (Denmark)

^c HOSPITAL TXAGORRITXU   (Spain)

^d UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALBUMIN; BRANCHED CHAIN AMINO ACID; LACTULOSE; NEOMYCIN;

ALBUMIN BLOOD LEVEL; DIARRHEA; DISEASE SEVERITY; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; HEPATIC ENCEPHALOPATHY; HUMAN; MORTALITY RATE; NAUSEA AND VOMITING; NITROGEN BALANCE; NUTRITIONAL STATUS; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK ASSESSMENT; RISK REDUCTION; SENSITIVITY ANALYSIS; SYSTEMATIC REVIEW; TREATMENT DURATION; TREATMENT OUTCOME; FEMALE; INTRAVENOUS DRUG ADMINISTRATION; MALE; META ANALYSIS; MORTALITY; NAUSEA; ORAL DRUG ADMINISTRATION; STATISTICAL BIAS;

ADMINISTRATION, ORAL; AMINO ACIDS, BRANCHED-CHAIN; BIAS (EPIDEMIOLOGY); DIARRHEA; FEMALE; HEPATIC ENCEPHALOPATHY; HUMANS; INJECTIONS, INTRAVENOUS; MALE; NAUSEA; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 85019616092     PISSN: None     EISSN: 1469493X     Source Type: Journal    
DOI: 10.1002/14651858.CD001939.pub4     Document Type: Review

References (114)

1. 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. Journal of Hepatology 1985;1:141-51. 2672562
2. Calvey H, Davis M, Williams R. Prospective study of nasogastric feeding via East Grinstead or Viomedex tubes compared with oral dietary supplementation in patients with cirrhosis. Clinical Nutrition 1984;3:63-6. 2672563
3. Williams R, Calvey H, Davis M. Controlled trial of nutritional supplementation in acute alcoholic hepatitis. In: Holm EKH editor(s). Metabolism and Nutrition in Liver Disease. Lancaster, UK: MTP Press, Ltd, 1985:361-8. 2672564
4. Cerra FB. Disease-specific amino acid infusion (F080) in hepatic encephalopathy: a prospective, randomized, double-blind, controlled trial [personal communication]. Correspondence with authors September 2002. 2672569
5. Cerra FB, Cheung NK, Fischer JE, Kaplowitz N, Schiff E-R, Dienstag JL, et al. Disease-specific amino acid infusion (F080) in hepatic encephalopathy: a prospective, randomized, double-blind, controlled trial. JPEN. Journal of Parenteral and Enteral Nutrition 1985;9:288-95. 2672566
6. Cerra FB, Cheung NK, Fischer JE, Kaplowitz N, Schiff ER, Dienstag JL, et al. A multicenter trial of branched chain enriched amino acid infusion (F080) in hepatic encephalopathy (HE). Hepatology (Baltimore, Md.) 1982;2:699. 2672567
7. Cerra FB, McMillen M, Angelico R, Cline B, Lyons J, Faulkenbach L, et al. Cirrhosis, encephalopathy, and improved results with metabolic support. Surgery 1983;94:612-9. 2672568
8. Egberts EH, Hamster W, Schomeerus H, Jürgens P. Effect of branched chain amino acids on latent porto-systemic-encephalopathy (PSE). JPEN. Journal of Parenteral and Enteral Nutrition 1981;5:5. 2672571
9. Egberts EH, Schomeerus H, Hamster W, Jürgens P. Effective treatment of latens porto-systemic encephalopathy with oral branched chain amino acids. In: Capocaccia L, Fischer JE, Rossi-Fanelli F editor(s). Hepatic Encephalopathy in Chronic Liver Failure. New York: Plenum Press, 1984:351-7. 2672572
10. Egberts EH, Schomerus H, Hamster W, Jurgens P. Branched chain amino acids in the treatment of latent portosystemic encephalopathy. A double-blind placebo-controlled crossover study. Gastroenterology 1985;88:887-95. 2672574
11. Egberts EH, Schomerus H, Hamster W, Jürgens P. Branched-chain amino acids in the treatment of latent porto-systemic encephalopathy. A placebo-controlled double-blind cross-over study [Verzweigtkettige Aminosäuren bei der behandlung der latenten portosystemischen enzephalopathie. Eine placebokontrollierte doppelblind-cross-over-studie]. Zeitschrift für Ernährungswissenschaft 1986;25:9-28. 2672573
12. Hamster W, Egberts EH, Hamster H. Treatment with branched-chain amino acids and effect on psycho-physical capacity functions in latent porto-systemic encephalopathy [Behandlung mit verzweigtkettigen aminosäuren und ihre auswirkung auf psychophysische leistungsfunktionen bei latenter portosystemischer enzephalopathie]. Arzneimittelforschung 1982;32:901-2. 2672575
13. Fiaccadori F. Branched chain amino acid enriched solutions in the treatment of hepatic encephalopathy: a controlled trial. Italian Journal of Gastroenterology (additional information from author November 2012). 2672581
14. Fiaccadori F, Ghinelli F, Pedretti G. Branched chain amino acid enriched solutions in the treatment of hepatic encephalopathy: a controlled trial. Italian Journal of Gastroenterology 1985;17:5-10. 2672579
15. Fiaccadori F, Ghinelli F, Pedretti G, Mancia D. Mental state course and biochemical findings in HE treated by BCAA-enriched mixtures. In: Holm E, Kasper H editor(s). Metabolism and Nutrition in Liver Disease Freiburg 1984: Proceedings of the 41st Falk Symposium. Lancaster: MTP Press, 1985:281-5. 2672577
16. Fiaccadori F, Ghinelli F, Pedretti G, Pelosi G, Sacchini D, Zeneroli ML, et al. Branched chain amino acid enriched solutions in the treatment of hepatic encephalopathy: a controlled trial. In: Capocaccia L, Fischer JE, Rossi-Fanelli F editor(s). Hepatic Encephalopathy in Chronic Liver Failure. New York: Plenum Press, 1984:323-33. 2672578
17. Fiaccadori F, Ghinelli F, Pelosi G, Sacchini D, Vaona G, Zeneroli ML, et al. Selective amino acid solutions in hepatic encephalopathy treatment (a preliminary report). La Ricerca in Clinica e in Laboratorio 1980;10:411-22. [MEDLINE: 81102770]2672580
18. Hayashi S, Aoyagi Y, Fujiwara K, Oka H, Oda T. A randomized controlled trial of branched-chain amino acid (BCAA)-enriched elemental diet (ED-H) for hepatic encephalopathy. Journal of Gastroenterology and Hepatology 1991;6:191. 2672583
19. Horst D, Grace N, Conn HO, Schiff E, Schenker S, Viteri A, et al. A double-blind randomized comparison of dietary protein and an oral branched chain amino acid (BCAA) solution in cirrhotic patients with chronic portal-systemic encephalopathy (PSE) [IASL abstract]. Hepatology (Baltimore, Md.) 1982;2:184. 2672585
20. Horst D, Grace ND, Conn HO, Schiff E, Schenker S, Viteri A, et al. Comparison of dietary protein with an oral, branched chain-enriched amino acid supplement in chronic portal-systemic encephalopathy: a randomized controlled trial. Hepatology (Baltimore, Md.) 1984;4:279-87. 2672586
21. Hwang SJ, Chan CY, Wu JC, Lee SD, Huan YS, Tsai YT, et al. A randomized controlled trial for the evaluation of the efficacy of branched chain amino acid-enriched amino acid solution in the treatment of patients with hepatic encephalopathy. Chinese Journal of Gastroenterology 1988;5:185-92. 2672588
22. Les I, Doval E, Garcia-Martinez R, Planas M, Cardenas G, Gomez P, et al. Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: a randomized study. American Journal of Gastroenterology 2011;106:1081-8. 2672590
23. Bianchi GP, Marchesini G, Zoli M, Abbiati R, Ferrario E, Fabbri A, et al. Oral BCAA supplementation in cirrhosis with chronic encephalopathy: effects on prolactin and estradiol levels. Hepato-gastroenterology 1992;39:443-6. 2672592
24. Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology 2003;124:1792-801. 2672593
25. Marchesini G, Dioguardi FS, Bianchi GP, Zoli M, Bellati G, Roffi L, et al. Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy. A randomized double-blind casein controlled trial. The Italian Multicenter Study Group. Journal of Hepatology 1990;11:92-101. 2672594
26. Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology 2003;124:1980-2. 2672596
27. 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;5:282-9. 2672598
28. Michel H, Pomier-Layrargues G, Aubin JP, Bories P, Mirouze D, Bellet-Herman H. Treatment of hepatic encephalopathy by infusion of a modified amino acid solution: results of a controlled study in 47 cirrhotic patients. In: Capocaccia L, Fischer JE, Rossi-Fanelli F editor(s). Hepatic Encephalopathy in Chronic Liver Failure. New York: Plenum Press, 1984:301-10. 2672599
29. Michel H, Pomier-Layrargues G, Duhamel O, Lacombe B, Cuilleret G, Bellet-Hermann H. Intravenous infusion of ordinary and modified amino-acid solutions in the management of hepatic encephalopathy (controlled study, 30 patients). Gastroenterology 1980;79:1038. 2672600
30. Pomier-Layrargues G, Duhamel O, Lacombe B, Cuilleret G, Bellet H, Michel H. Intravenous infusion of ordinary and modified amino-acid solutions in the management of hepatic encephalopathy. Liver 1981;1:140. 2672601
31. Horie-Takashi I. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clinical Gastroenterology and Hepatology 2005; Vol. 3:705-13 (additional information and data received November 2011). 2672603
32. Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clinical Gastroenterology and Hepatology 2005;3:705-13. 2672604
33. Sato S, Watanabe A, Muto Y, Suzuki K, Kato A, Moriwaki H, et al. Clinical comparison of branched-chain amino acid (l-Leucine, l-Isoleucine, l-Valine) granules and oral nutrition for hepatic insufficiency in patients with decompensated liver cirrhosis (LIV-EN study). Hepatology Research 2005;31:232-40. 2672605
34. Plauth M, Egberts E-H, Hamster W, Török M, Müller P, Brand O, et al. Long-term treatment with branched-chain amino acids (BCA) improves the portosystemic encephalopathy (PSE) in ambulant patients. Results of a double blind, placebo controlled crossover study. Klinische Wochenschrift 1992;69:126. 2672607
35. Plauth M, Egberts EH, Hamster W, Török M, Müller PH, Brand O, et al. Long-term treatment of latent portosystemic encephalopathy with branched-chain amino acids. A double-blind placebo-crossover study. Journal of Hepatology 1993;17:308-14. 2672608
36. Riggio O, Cangiano C, Cascino A, Merli M, Stortoni M, Rossi-Fanelli F, et al. Long term dietary supplement with branched chain amino acids: a new approach in the prevention of hepatic encephalopathy: results of a controlled study in cirrhotics with porto-caval anastomosis. In: Associazione Italiana per Lo Studio del Fegato. Congress, editor(s). Hepatic Encephalopathy in Chronic Liver Failure. New York: Plenum Press, 1984:183-92. 2672610
37. Rossi-Fanelli F, Cangiano C, Capocaccia L, Cascino A, Ceci F, Muscaritoli M, et al. Use of branched chain amino acids for treating hepatic encephalopathy: clinical experiences. Gut 1986;27:111-5. 2672611
38. Rossi-Fanelli F, Cangiano C, Cascino A, Merli M, Riggio O, Stortoni M, et al. Branched-chain amino acids in the treatment of severe hepatic encephalopathy. In: Capocaccia L, Fischer JE, Rossi-Fanelli F editor(s). Hepatic Encephalopathy in Chronic Liver Failure. New York: Plenum Press, 1984:335-44. 2672612
39. Rossi-Fanelli F, Riggio O, Cangiano C, Cascino A, De Conciliis D, Merli M, et al. Branched-chain amino acids vs lactulose in the treatment of hepatic coma: a controlled study. Digestive Diseases and Sciences 1982;27:929-35. 2672613
40. Strauss E, Cartapatti Da Silva E, Lacet CM, Capacci MLL, Bernardini AP. Treatment of hepatic encephalopathy: a randomized clinical trial comparing a branched chain enriched amino acid solution to oral neomycin. Nutritional Support Services 1986;6:18-21. 2672615
41. Strauss E, Santos WR, Da Silva EC, Lacet CM, Capacci LL, Bernardini AP. A randomized controlled clinical trial for the evaluation of the efficacy of an enriched branched-chain amino-acid solution compared to neomycin in hepatic encephalopathy. Hepatology (Baltimore, Md.) 1983;3:862. 2672616
42. Gluud C, Dejgaard A, Hardt F, Kristensen M, Køhler O, Melgaard B, et al. Preliminary treatment results with balanced amino acid infusion to patients with hepatic encephalopathy. Scandinavian Journal of Gastroenterology 1983;18:19. 2672618
43. Vilstrup H, Gluud C, Hardt F, Kristensen M, Køhler O, Melgaard B, et al. Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy. A double-blind study of 65 patients with cirrhosis. Hepatology (Baltimore, Md.) 1990;10:291-6. 2672619
44. Vilstrup H, Gluud C, Hardt F, Kristensen M, Melgaard B, Køhler O, et al. Branched chain enriched amino acid nutrition does not change the outcome of hepatic coma in patients with cirrhosis of the liver. Journal of Hepatology 1985;1:S347. 2672620
45. Eriksson LS, Persson A, Wahren J. Branched-chain amino acids in the treatment of chronic hepatic encephalopathy. Gut 1982;23:801-6. 2672622
46. Hayashi M, Ikezawa K, Ono A, Okabayashi S, Hayashi Y, Shimizu S, et al. Evaluation of the effects of combination therapy with branched-chain amino acid and zinc supplements on nitrogen metabolism in liver cirrhosis. Hepatology Research 2007;37:615-19. 2672624
47. Malaguarnera M, Risino C, Cammalleri L, Malaguarnera L, Astuto M, Vecchio I, et al. Branched chain amino acids supplemented with L-acetylcarnitine versus BCAA treatment in hepatic coma: a randomized and controlled double blind study. European Journal of Gastroenterology & Hepatology 2009;21:762-70. 2672626
48. O'Keefe SJ, Ogden J, Dicker J. Enteral and parenteral branched chain amino acid-supplemented nutritional support in patients with encephalopathy due to alcoholic liver disease. JPEN. Journal of Parenteral and Enteral Nutrition 1987;11:447-53. 2672628
49. Wahren J, Denis J, Desurmont P, Eriksson LS, Escoffier JM, Gauthier AP, et al. Is intravenous administration of branched chain amino acids effective in the treatment of hepatic encephalopathy? A multicenter study. Hepatology (Baltimore, Md.) 1983;3:475-80. 2672630
50. Walker S, Gotz R, Czygan P, Stiehl A, Lanzinger G, Sieg A, et al. Oral keto analogs of branched-chain amino acids in hyperammonemia in patients with cirrhosis of the liver. A double-blind crossover study. Digestion 1982;24:105-11. 2672632
51. The effects of supplementation with synbiotics, branched chain amino acids on levels of hepatic encephalopathy in patients with cirrhosis. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12610001021066 (accessed 10 May 2017). 2672634
52. Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology (Baltimore, Md.) 2014;60:715-35.
53. American Association for the Study of Liver Diseases, European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. Journal of Hepatology 2014;61:642-59.
54. Amodio P, Campagna F, Olianas S, Iannizzi P, Mapelli D, Penzo M, et al. Detection of minimal hepatic encephalopathy: normalization and optimization of the Psychometric Hepatic Encephalopathy Score. A neuropsychological and quantified EEG study. Journal of Hepatology 2008;49(3):346-53. [PUBMED: 18602716]
55. Amodio P, Canesso F, Montagnese S. Dietary management of hepatic encephalopathy revisited. Current Opinion in Clinical Nutrition and Metabolic Care 2014;17(5):448-52. [PUBMED: 25025262]
56. Bajaj JS. Minimal encephalopathy matters in daily life. World Journal of Gastroenterology 2008;14(23):3609-15.
57. Bajaj JS. Review article: the modern management of hepatic encephalopathy. Alimentary Pharmacology & Therapeutics 2010;31(5):537-47. [PUBMED: 20002027]
58. Bajaj JS, Cordoba J, Mullen KD, Amodio P, Shawcross DL, Butterworth RF, et al. Review article: the design of clinical trials in hepatic encephalopathy - an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement. Alimentary Pharmacology & Therapeutics 2011;33(7):739-47. [PUBMED: 21306407]
59. Bak LK, Schousboe A, Waagepetersen HS. The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. Journal of Neurochemistry 2006;98:641-53.
60. Blei AT, Córdoba J, Practice Parameters Committee of the American College of Gastroenterology. Hepatic encephalopathy. American Journal of Gastroenterology 2001;96:1986-76.
61. Córdoba J, López-Hellín J, Planas M, Sabín P, Sanpedro F, Castro F, et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. Journal of Hepatology 2004;41:38-43.
62. Dam G, Keiding S, Munk OL, Ott P, Buhl M, Vilstrup H, et al. Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects. American Journal of Physiology. Gastrointestinal and Liver Physiology 2011;301(2):G269-77. [PUBMED: 21636533]
63. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical Research Ed.) 1997;315(7109):629-34. [PUBMED: 9310563]
64. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy - definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology (Baltimore, Md.) 2002;35(3):716-21. [PUBMED: 11870389]
65. Fichet J, Mercier E, Genée O, Garot D, Legras A, Dequin PF, et al. Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy. Journal of Critical Care 2009;24:364-70.
66. García-Martínez R, Córdoba J. Acute-on-chronic liver failure: the brain. Current Opinion in Critical Care 2011;17(2):177-83.
67. Gluud C. Branched-chain amino acids for hepatic encephalopathy?. Hepatology (Baltimore, Md.) 1991;13(4):812-3.
68. Gluud LL, Langholz E, Krag A. Meta-analysis: isosorbide-mononitrate alone or with either beta-blockers or endoscopic therapy for the management of oesophageal varices. Alimentary Pharmacology & Therapeutics 2010;32(7):859-71. [PUBMED: 20839387]
69. Gluud LL, Dam G, Borre M, Les I, Cordoba J, Marchesini G, et al. Oral branched-chain amino acids have a beneficial effect on manifestations of hepatic encephalopathy in a systematic review with meta-analyses of randomized controlled trials. Journal of Nutrition 2013;143:1263-8. [PUBMED: 23739310]
70. Gluud LL, Dam G, Borre M, Les I, Cordoba J, Marchesini G, et al. Lactulose, rifaximin or branched chain amino acids for hepatic encephalopathy: what is the evidence?. Metabolic Brain Disease 2013;28(2):221-5. [PUBMED: 23275147]
71. Gluud C, Nikolova D, Klingenberg SL, Alexakis N, Als-Nielsen B, Colli A, et al. Cochrane Hepato-Biliary Group. About The Cochrane Collaboration (Cochrane Review Groups (CRGs)). 2017, Issue 4. Art. No.: LIVER.
72. Brozek J, Oxman A, Schünemann H. GRADEpro. Version 3.2 for Windows. Grade Working Group 2004-2007, 2008.
73. Guerit JM, Amantini A, Fischer C, Kaplan PW, Mecarelli O, Schnitzler A, et al. Neurophysiological investigations of hepatic encephalopathy: ISHEN practice guidelines. Liver International 2009;29(6):789-96. [PUBMED: 19638107]
74. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ (Clinical Research Ed.) 2008;336(7650):924-6. [PUBMED: 18436948]
75. Harbord RM, Egger M, Sterne JA. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Statistics in Medicine 2006;25(20):3443-57. [PUBMED: 16345038]
76. Higgins JP, White IR, Wood AM. Imputation methods for missing outcome data in meta-analysis of clinical trials. Clinical Trials 2008;5:225-39.
77. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
78. Higgins JP, Whitehead A, Simmonds M. Sequential methods for random-effects meta-analysis. Statistics in Medicine 2011;30(9):903-21. [PUBMED: 21472757]
79. Holecek M. Three targets of branched-chain amino acid supplementation in the treatment of liver disease. Nutrition (Burbank, Los Angeles County, Calif.) 2010;26(5):482-90. [PUBMED: 20071143]
80. Holecek M, Kandar R, Sispera L, Kovarik M. Acute hyperammonemia activates branched-chain amino acid catabolism and decreases their extracellular concentrations: different sensitivity of red and white muscle. Amino Acids 2011;40(2):575-84. [PUBMED: 20614225]
81. Holecek M. Branched-chain amino acids and ammonia metabolism in liver disease: therapeutic implications. Nutrition (Burbank, Los Angeles County, Calif.) 2013;29(10):1186-91. [PUBMED: 23756281]
82. Holecek M. Evidence of a vicious cycle in glutamine synthesis and breakdown in pathogenesis of hepatic encephalopathy-therapeutic perspectives. Metabolic Brain Disease 2014;29(1):9-17. [PUBMED: 23996300]
83. International Conference on Harmonisation Expert Working Group. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Guideline for good clinical practice CFR & ICH Guidelines. Vol. 1, Philadelphia (PA): Barnett International/PAREXEL, 1997.
84. Kachaamy T, Bajaj JS. Diet and cognition in chronic liver disease. Current Opinion Gastroenterology 2011;27:174-9.
85. Kawaguchi T, Taniguchi E, Sata M. Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis. Nutrition in Clinical Practice 2013;28(5):580-8. [PUBMED: 23945292]
86. Kircheis G, Fleig WE, Gortelmeyer R, Grafe S, Haussinger D. Assessment of low-grade hepatic encephalopathy: a critical analysis. Journal of Hepatology 2007;47(5):642-50. [PUBMED: 17869373]
87. Koretz RL, Avenell A, Lipman TO. Nutritional support for liver disease. Cochrane Database of Systematic Reviews 2012, Issue 5. [DOI: 10.1002/14651858.CD008344.pub2; PUBMED: 22592729]
88. Lathyris DN, Trikalinos TA, Ioannidis JP. Evidence from crossover trials: empirical evaluation and comparison against parallel arm trials. International Journal of Epidemiology 2007;36(2):422-30. [PUBMED: 17301102]
89. Methodological Expectations of Cochrane Intervention Reviews (MECIR). www.editorial-unit.cochrane.org/mecir (accessed 25 August 2015).
90. Metcalfe EL, Avenell A, Fraser A. Branched-chain amino acid supplementation in adults with cirrhosis and porto-systemic encephalopathy: systematic review. Clinical Nutrition (Edinburgh, Scotland) 2014;33(6):958-65. [PUBMED: 24656171]
91. Mullen KD. Review of the final report of the 1998 Working Party on definition, nomenclature and diagnosis of hepatic encephalopathy. Alimentary Pharmacology & Therapeutics 2007;25(Suppl 1):11-6. [PUBMED: 17295847]
92. Naylor CD, O'Rourke D, Detsky AS, Baker JP. Parenteral nutrition with branched-amino acids in hepatic encephalopathy. A meta-analysis. Gastroenterology 1989;97:1033-42.
93. Olde Damink SW, Jalan R, Redhead DN, Hayes PC, Deutz NE, Soeters PB. Interorgan ammonia and amino acid metabolism in metabolically stable patients with cirrhosis and a TIPSS. Hepatology (Baltimore, Md.) 2002;36(5):1163-71. [PUBMED: 12395326]
94. Rakoski MO, McCammon RJ, Piette JD, Iwashyna TJ, Marrero JA, Lok AS, et al. Burden of cirrhosis on older Americans and their families: analysis of the health and retirement study. Hepatology (Baltimore, Md.) 2012;55(1):184-91. [PUBMED: 21858847]
95. Randolph C, Hilsabeck R, Kato A, Kharbanda P, Li YY, Mapelli D, et al. Neuropsychological assessment of hepatic encephalopathy: ISHEN practice guidelines. Liver International 2009;29(5):629-35. [PUBMED: 19302444]
96. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
97. Roman E, Torrades MT, Nadal MJ, Cardenas G, Nieto JC, Vidal S, et al. Randomized pilot study: effects of an exercise programme and leucine supplementation in patients with cirrhosis. Digestive Diseases and Sciences 2014;59(8):1966-75. [PUBMED: 24599772]
98. Royle P, Milne R. Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches. International Journal of Technology Assessment in Health Care 2003;19(4):591-603.
99. Savovic J, Jones HE, Altman DG, Harris RJ, Juni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Annals of Internal Medicine 2012;157(6):429-38. [PUBMED: 22945832]
100. Stata Corp. Stata 13. Texas: Stata Corp, 2007.
101. Stepanova M, Mishra A, Venkatesan C, Younossi ZM. In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States from 2005 to 2009. Clinical Gastroenterology and Hepatology 2012;10(9):1034-41.e1. [PUBMED: 22642955]
102. Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C. User manual for Trial Sequential Analysis (TSA). ctu.dk/tsa/files/tsa_manual.pdf 2011 (accessed 23 April 2013).
103. Copenhagen Trial Unit. TSA - Trial Sequential Analysis. Version 0.9 Beta. Copenhagen: Copenhagen Trial Unit, 2011.
104. Tygstrup N, Vilstrup H. Effect of branched chain amino acids on the outcome of hepatic encephalopathy. Advances in Hepatic Encephalopathy and Urea Cycle Diseases. Basel: Karger, 1984:11-4.
105. Wein C, Koch H, Popp B, Oehler G, Schauder P. Minimal hepatic encephalopathy impairs fitness to drive. Hepatology (Baltimore, Md.) 2004;39:739-45.
106. Weir MC, Grimshaw JM, Mayhew A, Fergusson D. Decisions about lumping vs. splitting of the scope of systematic reviews of complex interventions are not well justified: a case study in systematic reviews of health care professional reminders. Journal of Clinical Epidemiology 2012;65(7):756-63. [PUBMED: 22498429]
107. Weissenborn K. Psychometric tests for diagnosing minimal hepatic encephalopathy. Metabolic Brain Disease 2013;28:227-9.
108. Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. Journal of Clinical Epidemiology 2008;61(1):64-75. [PUBMED: 18083463]
109. Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in a random-effects meta-analysis. BMC Medical Research Methodology 2009;9:86.
110. Wood L, Egger M, Gluud LL, Schulz KF, Juni P, Altman DG, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ (Clinical Research Ed.) 2008;336(7644):601-5. [PUBMED: 18316340]
111. Wright G, Jalan R. Management of hepatic encephalopathy in patients with cirrhosis. Best Practice & Research Clinical Gastroenterology 2007;21:95-110.
112. Als-Nielsen B, Koretz RL, Gluud LL, Gluud C. Branched-chain amino acids for hepatic encephalopathy. Cochrane Database of Systematic Reviews 2003, Issue 1. [DOI: 10.1002/14651858.CD001939]
113. Gluud LL, Dam G, Les I, Córdoba J, Marchesini G, Borre M, Aagaard NK, Vilstrup H. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database of Systematic Reviews 2015, Issue 2. [DOI: 10.1002/14651858.CD001939.pub2]
114. Gluud LL, Dam G, Les I, Córdoba J, Marchesini G, Borre M, et al. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database of Systematic Reviews 2015, Issue 9. [DOI: 10.1002/14651858.CD001939.pub3]