Combination of branched-chain amino acids and angiotensin-converting enzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: A randomized control trial

  • Authors:
    • Hitoshi Yoshiji
    • Ryuichi Noguchi
    • Yasuhide Ikenaka
    • Kosuke Kaji
    • Yosuke Aihara
    • Masaharu Yamazaki
    • Junichi Yamao
    • Masahisa Toyohara
    • Akira Mitoro
    • Masayoshi Sawai
    • Motoyuki Yoshida
    • Chie Morioka
    • Masao Fujimoto
    • Masahito Uemura
    • Hiroshi Fukui
  • View Affiliations

  • Published online on: August 24, 2011     https://doi.org/10.3892/or.2011.1433
  • Pages: 1547-1553
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Abstract

Insulin resistance (IR) is reportedly involved in the progression of hepatocellular carcinoma (HCC). Since neovascularization plays an important role in hepatocarcinogenesis and IR, an angiostatic therapy may be considered as one of the promising approaches for chemoprevention against HCC. The aim of the current study was to examine the combination effect of a clinically used branched-chain amino acid (BCAA) and an angiotensin-converting enzyme inhibitor (ACE-I), both reportedly possess anti-angiogenic and IR-improving activities, on the cumulative recurrence after curative therapy. BCAA granules (Livact; 12 g/day) and/or ACE-I (perindopril; 4 mg/day) were administered after the curative therapy for HCC, and several indices were analyzed. A 48-month follow-up revealed that the combination treatment with BCAA and ACE-I markedly inhibited the cumulative recurrence of HCC under IR conditions, whereas neither single treatment exerted a significant inhibition. The soluble form of the vascular endothelial growth factor (VEGF; a central angiogenic factor) receptor-2 (sVEGFR2) was significantly decreased only three months after the treatment without recurrence. We also observed that IR, determined by the homeostasis model assessment (HOMA-IR), was significantly improved by this regimen, indicating that an inhibitory effect was achieved, at least partly, by coordinated effects of anti-angiogenesis and IR improvement. In conclusion, since both BCAA and ACE-I are widely used in clinical practice with safety, this combination therapy may represent a potential new strategy for chemoprevention against IR-based HCC recurrence in the future. Moreover, sVEGFR2 may become a useful clinical predictive marker of this combination treatment.

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November 2011
Volume 26 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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APA
Yoshiji, H., Noguchi, R., Ikenaka, Y., Kaji, K., Aihara, Y., Yamazaki, M. ... Fukui, H. (2011). Combination of branched-chain amino acids and angiotensin-converting enzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: A randomized control trial. Oncology Reports, 26, 1547-1553. https://doi.org/10.3892/or.2011.1433
MLA
Yoshiji, H., Noguchi, R., Ikenaka, Y., Kaji, K., Aihara, Y., Yamazaki, M., Yamao, J., Toyohara, M., Mitoro, A., Sawai, M., Yoshida, M., Morioka, C., Fujimoto, M., Uemura, M., Fukui, H."Combination of branched-chain amino acids and angiotensin-converting enzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: A randomized control trial". Oncology Reports 26.6 (2011): 1547-1553.
Chicago
Yoshiji, H., Noguchi, R., Ikenaka, Y., Kaji, K., Aihara, Y., Yamazaki, M., Yamao, J., Toyohara, M., Mitoro, A., Sawai, M., Yoshida, M., Morioka, C., Fujimoto, M., Uemura, M., Fukui, H."Combination of branched-chain amino acids and angiotensin-converting enzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: A randomized control trial". Oncology Reports 26, no. 6 (2011): 1547-1553. https://doi.org/10.3892/or.2011.1433