Skip to main content
SpringerLink
Log in

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

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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].

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  29. Ginès P, Cárdenas A, Arroyo V, Rodés J. Management of cirrhosis and ascites. N Engl J Med. 2004;350:1646–54.

    Article  PubMed  Google Scholar 

  30. Buerk CA, Putnam CW, Starzl TE. Major hepatic resection and portal pressure. Surg Gynecol Obstet. 1977;144:853–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This study was supported in part by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant numbers 26830081 to Yukihiko Hiroshima and 24592009 to Kuniya Tanaka.

Author information

Authors and Affiliations

  1. Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan

    Yutaro Kikuchi MD, Yukihiko Hiroshima MD, PhD, Kenichi Matsuo MD, PhD, Daisuke Kawaguchi MD, Takashi Murakami MD, Keiji Koda MD, PhD & Kuniya Tanaka MD, PhD

  2. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Yasuhiro Yabushita MD, Itaru Endo MD, PhD & Kuniya Tanaka MD, PhD

  3. Department of Biostatistics and Epidemiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Masataka Taguri PhD

Authors
  1. Yutaro Kikuchi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yukihiko Hiroshima MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenichi Matsuo MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daisuke Kawaguchi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takashi Murakami MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yasuhiro Yabushita MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Itaru Endo MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Masataka Taguri PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Keiji Koda MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kuniya Tanaka MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kuniya Tanaka MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kikuchi, Y., Hiroshima, Y., Matsuo, K. et al. A Randomized Clinical Trial of Preoperative Administration of Branched-Chain Amino Acids to Prevent Postoperative Ascites in Patients with Liver Resection for Hepatocellular Carcinoma. Ann Surg Oncol 23, 3727–3735 (2016). https://doi.org/10.1245/s10434-016-5348-3

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-016-5348-3

Keywords

Search

Navigation