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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 11/2016

01-10-2016 | Hepatobiliary Tumors

A Randomized Clinical Trial of Preoperative Administration of Branched-Chain Amino Acids to Prevent Postoperative Ascites in Patients with Liver Resection for Hepatocellular Carcinoma

Authors: Yutaro Kikuchi, MD, Yukihiko Hiroshima, MD, PhD, Kenichi Matsuo, MD, PhD, Daisuke Kawaguchi, MD, Takashi Murakami, MD, Yasuhiro Yabushita, MD, Itaru Endo, MD, PhD, Masataka Taguri, PhD, Keiji Koda, MD, PhD, Kuniya Tanaka, MD, PhD

Published in: Annals of Surgical Oncology | Issue 11/2016

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Abstract

Background

Massive postoperative ascites remains a major threat that can lead to liver failure and other fatal complications, especially in patients with poor liver function. Branched-chain amino acid (BCAA) administration increases biosynthesis and secretion of albumin by hepatocytes and increases oncotic pressure by elevating blood albumin concentration, thereby decreasing peripheral edema, ascites, and pleural effusion.

Method

We randomly allocated consecutive patients undergoing major liver resection for hepatocellular carcinoma to either a group where oral BCAA administration was initiated 3 weeks before liver resection, or a non-BCAA group. The primary study endpoint was development of postoperative ascites.

Results

Overall, 39 patients were allocated to the BCAA group, while 38 were assigned to the non-BCAA group. No significant difference in the rate of refractory ascites, considered alone, was evident between the BCAA (5.1 %) and non-BCAA groups (13.2 %; p = 0.263). However, the occurrence of refractory ascites and/or pleural effusion was significantly less frequent in the BCAA group (5.1 %) than in the non-BCAA group (21.1 %; p = 0.047). Furthermore, the postoperative serum concentration of reduced-state albumin was greater immediately after liver resection in the BCAA group than in the non-BCAA group.

Conclusion

Preoperative administration of BCAA did not significantly improve prevention of refractory ascites, but significant effectiveness in preventing ascites, pleural effusion, or both, as well as improving metabolism of albumin, was demonstrated [University Hospital Medical Information Network (UMIN) reference number 000004244].
Literature
1.
Ishizawa T, Hasegawa K, Kokudo N, et al. Risk factors and management of ascites after liver resection to treat hepatocellular carcinoma. Arch Surg. 2009;144:46–51.CrossRefPubMed
2.
Marchesini G, Zoli M, Angiolini A, Dondi C, Bianchi FB, Pisi E. Muscle protein breakdown in liver cirrhosis and the role of altered carbohydrate metabolism. Hepatology. 1981;1:294–9.CrossRefPubMed
3.
Yoshida T, Muto Y, Moriwaki H, Yamato M. Effect of long-term oral supplementation with branched-chain amino acid granules on the prognosis of liver cirrhosis. Gastroenterol Jpn. 1989;24:692–8.PubMed
4.
Marchesini G, Dioguardi FS, Bianchi GP, 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. J Hepatol. 1990;11:92–101.CrossRefPubMed
5.
Marchesini G, Bianchi G, Merli M, et al. Italian BCAA Study Group. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology. 2003;124:1792–801.CrossRefPubMed
6.
Muto Y, Sato S, Watanabe A, et al.; 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;3:705–13.
7.
Charlton M. Branched-chain amino acid enriched supplements as therapy for liver disease. J Nutr. 2006; 136 Suppl. 1:295s–8s.PubMed
8.
Moriwaki H, Miwa Y, Tajika M, Kato M, Fukushima H, Shiraki M. Branched-chain amino acids as a protein- and energy-source in liver cirrhosis. Biochem Biophys Res Commun. 2004;313:405–9.CrossRefPubMed
9.
Togo S, Tanaka K, Morioka D, et al. Usefulness of granular BCAA after hepatectomy for liver cancer complicated with liver cirrhosis. Nutrition. 2005;21:480–6.CrossRefPubMed
10.
Okabayashi T, Iyoki M, Sugimoto T, Kobayashi M, Hanazaki K. Oral supplementation with carbohydrate- and branched-chain amino acid-enriched nutrients improves postoperative quality of life in patients undergoing hepatic resection. Amino Acids. 2011;40:1213–20.CrossRefPubMed
11.
Ishikawa Y, Yoshida H, Mamada Y, et al. Prospective randomized controlled study of short-term perioperative oral nutrition with branched chain amino acids in patients undergoing liver surgery. Hepatogastroenterology. 2010;57:583–90.PubMed
12.
Togo S, Tanaka K, Matsuo K, Nagano Y, Ueda M, Morioka D, et al. Duration of antimicrobial prophylaxis in patients undergoing hepatectomy: a prospective randomized controlled trial using flomoxef. J Antimicrob Chemother. 2007;59:964–70.CrossRefPubMed
13.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.CrossRefPubMedPubMedCentral
14.
Rahbari NN, Garden OJ, Padbury R, et al. Post-hepatectomy haemorrhage: a definition and grading by the International Study Group of Liver Surgery (ISGLS). HPB (Oxford). 2011;13:528–35.CrossRefPubMedPubMedCentral
15.
Koch M, Garden OJ, Padbury R, et al. Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery. 2011;149:680–8.CrossRefPubMed
16.
Rahbari NN, Garden OJ, Padbury R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149:713–24.CrossRefPubMed
17.
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864–74.CrossRef
18.
Onodera T, Goseki N, Kosaki G. Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients [in Japanese with English abstract]. Nippon Geka Gakkai Zasshi. 1984;85:1001–5.PubMed
19.
Sogami M, Era S, Nagaoka S, et al. HPLC-studies on nonmercapt-mercapt conversion of human serum albumin. Int J Pept Protein Res. 1985;25:398–402.CrossRefPubMed
20.
Fischer JE, Funovics JM, Aguirre A, James JH, Keane JM, Wesdorp RI. The role of plasma amino acids in hepatic encephalopathy. Surgery. 1975;78:276–90.PubMed
21.
Ijichi C, Matsumura T, Tsuji T, Eto Y. Branched-chain amino acids promote albumin synthesis in rat primary hepatocytes through the mTOR signal transduction system. Biochem Biophys Res Commun. 2003;303:59–64.CrossRefPubMed
22.
Nishitani S, Takehara K, Fujitani S, Sonaka I. Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2005;288:G1292–300.CrossRefPubMed
23.
She P, Reid TM, Bronson SK, Vary TC, Hajnal A, Lynch CJ, et al. Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab. 2007;6:181–94.CrossRefPubMedPubMedCentral
24.
Okuno M, Moriwaki H, Kato M, Muto Y, Kojima S. Changes in the ratio of branched-chain to aromatic amino acids affect the secretion of albumin in cultured rat hepatocytes. Biochem Biophys Res Commun. 1995;214:1045–50.CrossRefPubMed
25.
Elias-Miró M, Jiménez-Castro MB, Rodés J, Peralta C. Current knowledge on oxidative stress in hepatic ischemia/reperfusion. Free Radic Res. 2013;47:555–68.CrossRefPubMed
26.
Bruschi M, Candiano G, Santucci L, Ghiggeri GM. Oxidized albumin. The long way of a protein of uncertain function. Biochim Biophys Acta. 2013;1830:5473–9.CrossRefPubMed
27.
Fukushima H, Miwa Y, Shiraki M, et al. Oral branched-chain amino acid supplementation improves the oxidized/reduced albumin ratio in patients with liver cirrhosis. Hepatol Res. 2007;37:765–70.CrossRefPubMed
28.
Arroyo V, Ginès P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology. 1996;23:164–76.PubMed
29.
Ginès P, Cárdenas A, Arroyo V, Rodés J. Management of cirrhosis and ascites. N Engl J Med. 2004;350:1646–54.CrossRefPubMed
30.
31.
Kanematsu T, Takenaka K, Furuta T, Ezaki T, Sugimachi K, Inokuchi K. Acute portal hypertension associated with liver resection. Analysis of early postoperative death. Arch Surg. 1985;120:1303–5.CrossRefPubMed
32.
Lee SS, Hadengue A, Moreau R, Sayegh R, Hillon P, Lebrec D. Postprandial hemodynamic responses in patients with cirrhosis. Hepatology. 1988;8:647–51.CrossRefPubMed
33.
Gaiani S, Bolondi L, Li Bassi S, Santi V, Zironi G, Barbara L. Effect of meal on portal hemodynamics in healthy humans and in patients with chronic liver disease. Hepatology. 1989;9:815–9.CrossRefPubMed
34.
Fan ST, Ng IO, Poon RT, Lo CM, Liu CL, Wong J. Hepatectomy for hepatocellular carcinoma: the surgeon’s role in long-term survival. Arch Surg. 1999;134:1124–30.CrossRefPubMed
Metadata
Title
A Randomized Clinical Trial of Preoperative Administration of Branched-Chain Amino Acids to Prevent Postoperative Ascites in Patients with Liver Resection for Hepatocellular Carcinoma
Authors
Yutaro Kikuchi, MD
Yukihiko Hiroshima, MD, PhD
Kenichi Matsuo, MD, PhD
Daisuke Kawaguchi, MD
Takashi Murakami, MD
Yasuhiro Yabushita, MD
Itaru Endo, MD, PhD
Masataka Taguri, PhD
Keiji Koda, MD, PhD
Kuniya Tanaka, MD, PhD
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 11/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5348-3

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