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Insulin resistance (IR) is reportedly involved in the progression of hepatocellularcarcinoma (HCC). Since neovascularization plays an important role in hepatocarcinogenesisand IR, an angiostatic therapy may be considered as one of the promising approachesfor chemoprevention against HCC. The aim of the current study was to examine thecombination effect of a clinically used branched-chain amino acid (BCAA) and anangiotensin-converting enzyme inhibitor (ACE-I), both reportedly possess anti-angiogenicand 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 administeredafter the curative therapy for HCC, and several indices were analyzed. A 48-monthfollow-up revealed that the combination treatment with BCAA and ACE-I markedlyinhibited the cumulative recurrence of HCC under IR conditions, whereas neithersingle treatment exerted a significant inhibition. The soluble form of the vascularendothelial 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 effectwas achieved, at least partly, by coordinated effects of anti-angiogenesis andIR improvement. In conclusion, since both BCAA and ACE-I are widely used in clinicalpractice with safety, this combination therapy may represent a potential new strategyfor chemoprevention against IR-based HCC recurrence in the future. Moreover, sVEGFR2may become a useful clinical predictive marker of this combination treatment.

oncology reports

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