Surgery Today

, Volume 43, Issue 7, pp 720–726 | Cite as

Oral supplementation of branched-chain amino acids reduces early recurrence after hepatic resection in patients with hepatocellular carcinoma: a prospective study

  • Kengo Ichikawa
  • Takehiro OkabayashiEmail author
  • Hiromichi Maeda
  • Tsutomu Namikawa
  • Tatsuo Iiyama
  • Takeki Sugimoto
  • Michiya Kobayashi
  • Toshiki Mimura
  • Kazuhiro Hanazaki
Original Article



The long-term outcomes of branched-chain amino acids (BCAA) administration after hepatic resection in patients with hepatocellular carcinoma (HCC) remain unclear. This study assessed the effect of oral supplementation with BCAA on the development of liver tumorigenesis after hepatic resection in HCC patients.


Fifty-six patients were randomly assigned to receive either BCAA supplementation (Livact group, n = 26) or a conventional diet (Control group, n = 30). Twenty-six patients in the BCAA group were treated orally for 2 weeks before and 6 months after hepatic resection. Postoperative tumor recurrence was continuously evaluated in all patients by measuring various clinical parameters.


There was no significant difference in the overall survival rate between the two patient groups; however, the recurrence rate at 30 months after surgery was significantly better in the Livact group in comparison to the Control group. Interestingly, the tumor markers, such as AFP and PIVKA-II, significantly decreased at 36 months after liver resection in the Livact group in comparison to the Control group.


Oral supplementation of BCAA reduces early recurrence after hepatic resection in patients with HCC. This treatment regimen offers potential benefits for clinical use in such patients, even in cases with a well-preserved preoperative liver function.


Branched-chain amino acids Tumorigenesis Liver cancer Hepatectomy Nutrition 



Supported by the Ministry of Education, Culture, Sports, Science, and Technology, and the Kochi University Discretionary Fund.

Conflict of interest

All authors have no conflicts of interest to declare.


  1. 1.
    Ogata S, Belghiti J, Varma D, Sommacale D, Maeda A, Dondero F, et al. Two hundred liver hanging maneuvers for major hepatectomy: a single-center experience. Ann Surg. 2007;245:31–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Richter S, Kollmar O, Schuld J, Moussavian MR, Igna D. Chirurgische Arbeitsgemeinschaft OP-Technik und OP-Strukturen (CAOP) of the Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie. Randomized clinical trial of efficacy and costs of three dissection devices in liver resection. Br J Surg. 2009;96:593–601.PubMedCrossRefGoogle Scholar
  3. 3.
    Okabayashi T, Nishimori I, Sugimoto T, Maeda H, Dabanaka K, Onishi S, et al. Effects of branched-chain amino acids-enriched nutrient support for patients undergoing liver resection for hepatocellular carcinoma. J Gastroenterol Hepatol. 2008;23:1869–73.PubMedCrossRefGoogle Scholar
  4. 4.
    Okabayashi T, Nishimori I, Sugimoto T, Iwasaki S, Akisawa N, Maeda H, et al. The benefit of the supplementation of perioperative branched-chain amino acids in patients with surgical management for hepatocellular carcinoma: a preliminary study. Dig Dis Sci. 2008;53:204–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Okabayashi T, Nishimori I, Yamashita K, Sugimoto T, Namikawa T, Maeda H, et al. Preoperative oral supplementation with carbohydrate and branched-chain amino acid-enriched nutrient improves insulin resistance in patients undergoing a hepatectomy: a randomized clinical trial using an artificial pancreas. Amino Acids. 2010;38:901–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Hanazaki K, Kajikawa S, Shimozawa N, Mihara M, Shimada K, Hiraguri M, et al. Survival and recurrence after hepatic resection of 386 consecutive patients with hepatocellular carcinoma. J Am Coll Surg. 2000;191:381–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Yoshiji H, Noguchi R, Kitade M, Kaji K, Ikenaka Y, Namisaki T, et al. Branched-chain amino acids suppress insulin-resistance-based hepatocarcinogenesis in obese diabetic rats. J Gastroenterol. 2009;44:483–91.PubMedCrossRefGoogle Scholar
  8. 8.
    Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, for the Long-Term Survival Study (LOTUS) Group, et al. Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis. Hepatol Res. 2006;35:204–14.PubMedGoogle Scholar
  9. 9.
    Iwasa J, Shimizu M, Shiraki M, Shirakami Y, Sakai H, Terakura Y, et al. Dietary supplementation with branched-chain amino acids suppresses diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/KsJ-db/db mice. Cancer Sci. 2010;101:460–7.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 11.
    Fan ST, Mau Lo C, Poon RT, Yeung C, Leung Liu C, Yuen WK, et al. Continuous improvement of survival outcomes of resection of hepatocellular carcinoma: a 20-year experience. Ann Surg. 2011;253:745–58.PubMedCrossRefGoogle Scholar
  12. 12.
    Moriwaki H, Shiraki M, Fukushima H, Shimizu M, Iwasa J, Naiki T, et al. Long-term outcome of branched-chain amino acid treatment in patients with liver cirrhosis. Hepatol Res. 2008;38:S102–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Chun JM, Kwon HJ, Sohn J, Kim SG, Park JY, Bae HI, et al. Prognostic factors after early recurrence in patients who underwent curative resection for hepatocellular carcinoma. J Surg Oncol. 2011;103:148–51.PubMedCrossRefGoogle Scholar
  14. 14.
    Togo S, Tanaka K, Morioka D, Sugita M, Ueda M, Miura Y, et al. Usefulness of granular BCAA after hepatectomy for liver cancer complicated with liver cirrhosis. Nutrition. 2005;21:480–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Nishitani S, Takehana 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.PubMedCrossRefGoogle Scholar
  16. 16.
    Kawaguchi T, Taniguchi E, Itou M, Sumie S, Oriishi T, Matsuoka H, et al. Branched-chain amino acids improve insulin resistance in patients with hepatitis C virus-related liver disease: report of two cases. Liver Int. 2007;27:1287–92.PubMedGoogle Scholar
  17. 17.
    Giovannucci E, Michaud D. The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology. 2007;132:2208–25.PubMedCrossRefGoogle Scholar
  18. 18.
    Murata K, Moriyama M. Isoleucine, an essential amino acid, prevents liver metastases of colon cancer by antiangiogenesis. Cancer Res. 2007;67:3263–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Eikesdal HP, Sugimoto H, Birrane G, Maeshima Y, Cooke VG, Kieran M, et al. Identification of amino acids essential for the antiangiogenic activity of tumstatin and its use in combination antitumor activity. Proc Natl Acad Sci USA. 2008;105:15040–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Poon RT, Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, et al. Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database. Ann Surg. 2004;240:698–708.PubMedGoogle Scholar
  21. 21.
    Poon RT, Fan ST, Yu WC, Lam BK, Chan FY, Wong J. A prospective longitudinal study of quality of life after resection of hepatocellular carcinoma. Arch Surg. 2001;136:693–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, Italian BCAA Study Group, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology. 2003;124:1792–801.PubMedCrossRefGoogle Scholar
  23. 23.
    Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, Long-Term Survival Study Group, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol. 2005;3:705–13.PubMedCrossRefGoogle Scholar
  24. 24.
    Giovannini I, Chiarla C, Giuliante F, Vellone M, Ardito F, Nuzzo G. The relationship between albumin, other plasma proteins and variables, and age in the acute phase response after liver resection in man. Amino Acids. 2006;31:463–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2012

Authors and Affiliations

  • Kengo Ichikawa
    • 1
  • Takehiro Okabayashi
    • 1
    Email author
  • Hiromichi Maeda
    • 1
  • Tsutomu Namikawa
    • 1
  • Tatsuo Iiyama
    • 1
  • Takeki Sugimoto
    • 1
  • Michiya Kobayashi
    • 1
  • Toshiki Mimura
    • 1
  • Kazuhiro Hanazaki
    • 1
  1. 1.Regenerative Medicine Group, Department of Surgery, Center for Innovative and Translational MedicineKochi Medical SchoolNankokuJapan

Personalised recommendations