Skip to main content

Advertisement

SpringerLink
Log in

Importance of branched-chain amino acids in patients with liver cirrhosis and advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The aim of this retrospective cohort study was to clarify the effect of a branched-chain amino acids (BCAA) on the liver function and the prognosis of Child-Pugh class (C-P) A and B liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) undergoing hepatic arterial infusion chemotherapy (HAIC).

Methods

Ninety-two adult Japanese patients with LC and aHCC underwent HAIC. They were in C-P A or B, and they showed multiple partial responses or stable disease. We excluded 11 patients classified as C-P C and 47 patients who showed no response. The patients were divided into an HAIC group receiving HAIC alone (n = 43) and a BCAA group treated with HAIC plus BCAA (n = 49). HAIC was delivered via the proper hepatic artery. The BCAA group also received oral administration of BCAA.

Results

In the BCAA group, serum albumin increased significantly after HAIC, while there were no significant changes in serum total bilirubin, serum aminotransferases, prothrombin time, ascites, and hepatic encephalopathy. The C-P score decreased significantly after HAIC compared with before HAIC in C-P B patients, although there was no significant change in C-P A patients. Survival of the BCAA group was significantly longer than that of the HAIC group, with the median survival time being 426 versus 272 days for C-P B patients, although there was no significant difference for C-P A patients.

Conclusions

Branched-chain amino acids might improve the survival and C-P score by increasing serum albumin in C-P B patients with aHCC receiving HAIC.

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
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Llover JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008) SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390

    Article  Google Scholar 

  2. Moreno-Aspitia A, Morton RF, Hillman DW, Lingle WL, Rowland KM Jr, Wiesenfeld M, Flynn PJ, Fitch TR, Perez EA (2009) Phase II trial of sorafenib in patients with metastatic breast cancer previously exposed to anthracyclines or taxanes: North Central Cancer Treatment Group and Mayo Clinic Trial N0336. J Clin Oncol 27:11–15

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  3. Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB (2006) Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24:4293–4300 (PMID: 16908937)

    Article  PubMed  CAS  Google Scholar 

  4. Pinter M, Sieghart W, Graziadei I, Vogel W, Maieron A, Königsberg R, Weissmann A, Kornek G, Plank C, Peck-Radosavljevic M (2009) Sorafenib in unresectable hepatocellular carcinoma from mild to advanced stage liver cirrhosis. Oncologist 14:70–76

    Article  PubMed  Google Scholar 

  5. Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Nakashima O, Kojiro M, Makuuchi M (2010) Management of hepatocellular carcinoma in Japan: consensus-based clinical practice guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis 29:339–364

    Article  Google Scholar 

  6. Toyoda H, Nakano S, Kumada T, Takeda I, Sugiyama K, Osada T, Kirishima S, Suga T, Takahashi M (1995) The efficacy of continuous local arterial infusion of 5-fluorouracil and cisplatin through an implanted reservoir for severe advanced hepatocellular carcinoma. Oncology 52:295–299

    Article  PubMed  CAS  Google Scholar 

  7. Murata K, Shiraki K, Kawakita T, Yamamoto N, Okano H, Nakamura M, Sakai T, Deguchi M, Ohmori S, Nakano T (2003) Low-dose chemotherapy of cisplatin and 5-fluorouracil or doxorubicin via implanted fusion port for unresectable hepatocellular carcinoma. Anticancer Res 23:1719–1722

    PubMed  CAS  Google Scholar 

  8. Okuda K, Tanaka M, Shibata J, Ando E, Ogata T, Kinoshita H, Eriguchi N, Aoyagi S, Takikawa K (1999) Hepatic arterial infusion chemotherapy with continuous low dose administration of cisplatin and 5-fluorouracil for multiple recurrence of hepatocellular carcinoma after surgical treatment. Oncol Rep 6:587–591

    PubMed  CAS  Google Scholar 

  9. Nagai H, Sumino Y (2008) Therapeutic strategy of advanced hepatocellular carcinoma by using combined intra-arterial chemotherapy. Recent Pat Anticancer Drug Discov 3:220–226

    Article  PubMed  CAS  Google Scholar 

  10. Nagai H, Kanayama M, Higami K, Momiyama K, Ikoma A, Okano N, Matsumaru K, Watanabe M, Ishii K, Sumino Y, Miki K (2007) Twenty-four hour intra-arterial infusion of 5-fluorouracil, cisplatin, and leucovorin is more effective than 6-hour infusion for advanced hepatocellular carcinoma. World J Gastroenterol 13:280–284

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Moriwaki H, Miwa Y, Tajika M, Kato M, Fukushima H, Shiraki M (2004) Branched-chain amino acids as a protein- and energy-source in liver cirrhosis. Biochem Biophys Res Commun 313:405–409

    Article  PubMed  CAS  Google Scholar 

  12. Kondrup J, Muller MJ (1997) Energy and protein requirements of patients with chronic liver disease. J Hepatol 27:239–247

    Article  PubMed  CAS  Google Scholar 

  13. Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, Rossi Fanelli F, Abbiati R (2003) Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology 124:1729–1801 (PMID: 12806613)

    Article  Google Scholar 

  14. Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, Kato M, Nakamura T, Higuchi K, Nishiguchi S, Kumada H (2005) Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol 3:705–713

    Article  PubMed  CAS  Google Scholar 

  15. Charlton M (2006) Branched-chain amino acid enriched supplements as therapy for liver disease. J Nutr 136:295S–298S

    PubMed  CAS  Google Scholar 

  16. Hayashi S, Chung H, Kudo M, Ishikawa E, Takita M, Ueda T, Kitani S, Inoue T, Yada N, Hagiwara S, Minami Y, Ueshima K (2011) Oral branched-chain amino acid granules reduce the incidence of hepatocellular carcinoma and improve event-free survival in patients with liver cirrhosis. Dig Dis 29:326–332

    Article  Google Scholar 

  17. Harima Y, Yamasaki T, Hamabe S, Saeki I, Okita K, Terai S, Sakaida I (2010) Effects of a late evening snack using branched-chain amino acid-enriched nutrients in patients undergoing hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma. Hepatol Res 40:574–584

    Article  PubMed  CAS  Google Scholar 

  18. Iwamiya T, Sawada S, Ohta Y (1994) Repeated arterial infusion chemotherapy for inoperable hepatocellular carcinoma using an implantable drug delivery system. Cancer Chemother Pharmacol 33:S134–S138

    Article  PubMed  Google Scholar 

  19. Yamasaki T, Kurokawa F, Shirahashi H et al (2002) Novel arterial infusion chemotherapy using cisplatin, 5-fluorouracil, and leucovorin for patients with advanced hepatocellular carcinoma. Hepatol Res 23:7–17

    Article  PubMed  CAS  Google Scholar 

  20. Italian Multicentre Cooperative Project on Nutrition in Liver Cirrhosis (1994) Nutritional status in cirrhosis. J Hepatol 21:317–325

    Article  Google Scholar 

  21. Swart GR, Zillikens MC, van Vuure JK, van den Berg JW (1989) Effect of a late evening meal on nitrogen balance in patients with cirrhosis of the liver. BMJ 299:1202–1203

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Zillikens MC, van den Berg JW, Wattimena JL, Rietveld T, Swart GR (1993) Nocturnal oral glucose supplementation. The effects on protein metabolism in cirrhotic patients and in healthy controls. J Hepatol 17:377–383

    Article  PubMed  CAS  Google Scholar 

  23. Miwa Y, Shiraki M, Kato M, Tajika M, Mohri H, Murakami N, Kato T, Ohnishi H, Morioku T, Muto Y, Moriwaki H (2000) Improvement of fuel metabolism by nocturnal energy supplementation in patients with liver cirrhosis. Hepatol Res 18:184–189

    Article  PubMed  Google Scholar 

  24. Nakaya Y, Okita K, Suzuki K, Moriwaki H, Kato A, Miwa Y, Shiraishi K, Okuda H, Onji M, Kanazawa H, Tsubouchi H, Kato S, Kaito M, Watanabe A, Habu D, Ito S, Ishikawa T, Kawamura N, Arakawa Y, Hepatic Nutritional Therapy (HNT) Study Group (2007) BCAA-enriched snack improves nutritional state of cirrhosis. Nutrition 23:113–120

    Article  PubMed  CAS  Google Scholar 

  25. Okamoto M, Sakaida I, Tsuchiya M, Suzuki C, Okita K (2003) Effect of late evening snack on the blood glucose level and energy metabolism in patients with liver cirrhosis. Hepatol Res 27:45–50

    Article  PubMed  Google Scholar 

  26. Sakaida I, Tsuchiya M, Okamoto M, Okita K (2004) Late evening snack and the change of blood glucose level in patients with liver cirrhosis. Hepatol Res 30S:67–72

    Article  PubMed  Google Scholar 

  27. Tsuchiya M, Sakaida I, Okamoto M, Okita K (2005) The effect of a late evening snack in patients with liver cirrhosis. Hepatol Res 31:95–103

    Article  PubMed  Google Scholar 

  28. Lam VW, Poon RT (2008) Role of branched-chain amino acids in management of cirrhosis and hepatocellular carcinoma. Hepatol Res 38:107–115

    Article  Google Scholar 

  29. Poon RT, Yu W, Fan S, Wong J (2004) Long-term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial. Aliment Pharmacol Ther 19:779–788

    Article  PubMed  CAS  Google Scholar 

  30. Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, Kato M, Nakamura T, Higuchi K, Nishiguchi S, Kumada H, Long-Term Survival Study Group (2005) Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol 3:705–713

    Article  PubMed  CAS  Google Scholar 

  31. Yoshida T, Muto Y, Moriwaki H, Yamato M (1989) Effect of long-term oral supplementation with branched-chain amino acid granules on the prognosis of liver cirrhosis. Gastroenterol Jpn 24:692–698

    PubMed  CAS  Google Scholar 

  32. Ijichi C, Matsumura T, Tsuji T, Eto Y (2003) Branched-chain amino acids promote albumin synthesis in rat primary hepatocytes through the mTOR signal transduction system. Biochem Biophys Res Commun 303:59–64

    Article  PubMed  CAS  Google Scholar 

  33. Matsumura T, Morinaga Y, Fujitani S, Takehara K, Nishitani S, Sonaka I (2005) Oral administration of branched-chain amino acids activates the mTOR signal in cirrhotic rat liver. Hepatol Res 33:27–32

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), Faculty of Medicine, School of Medicine, Toho University, 6-11-1, Omorinishi, Ota-ku, Tokyo, 143-8541, Japan

    Takenori Kanekawa, Hidenari Nagai, Masahiro Kanayama & Yasukiyo Sumino

Authors
  1. Takenori Kanekawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hidenari Nagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masahiro Kanayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasukiyo Sumino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hidenari Nagai.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kanekawa, T., Nagai, H., Kanayama, M. et al. Importance of branched-chain amino acids in patients with liver cirrhosis and advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy. Cancer Chemother Pharmacol 74, 899–909 (2014). https://doi.org/10.1007/s00280-014-2564-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-014-2564-z

Keywords

Search

Navigation