Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma.
OBJECTIVE
No chemopreventive agent has been approved against hepatocellular carcinoma (HCC) yet. Since neovascularization plays a pivotal role in HCC, an angiostatic agent is considered as one of the promising approaches. The aim of this study was to elucidate the combined effect of the clinically used vitamin K(2) (VK) and angiotensin-converting enzyme inhibitor (ACE-I) on cumulative recurrence after curative treatment on a total of 87 patients, especially in consideration of neovascularization.


METHODS
VK (menatetrenone; 45 mg/day) and/or ACE-I (perindopril; 4 mg/day) were administered for 36-48 months after curative therapy for HCC. The cumulative recurrence and several indices were analyzed.


RESULTS
A 48-month follow-up revealed that the combination treatment with VK and ACE-I markedly inhibited the cumulative recurrence of HCC in association with suppression of the serum level of the vascular endothelial growth factor (VEGF); a central angiogenic factor. The serum level of lectin-reactive alpha-fetoprotein was also suppressed almost in parallel with VEGF. These beneficial effects were not observed with single treatment using VK or ACE-I.


CONCLUSIONS
The combination treatment of VK and ACE-I may suppress the cumulative recurrence of HCC after the curative therapy, at least partly through suppression of the VEGF-mediated neovascularization.
Yoshiji
Hitoshi
H
Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8522, Japan. yoshijih@naramed-u.ac.jp
Noguchi
Ryuichi
R
Toyohara
Masahisa
M
Ikenaka
Yasuhide
Y
Kitade
Mitsuteru
M
Kaji
Kosuke
K
Yamazaki
Masaharu
M
Yamao
Junichi
J
Mitoro
Akira
A
Sawai
Masayoshi
M
Yoshida
Motoyuki
M
Fujimoto
Masao
M
Tsujimoto
Tatsuhiro
T
Kawaratani
Hideto
H
Uemura
Masahito
M
Fukui
Hiroshi
H
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000628:therapy; D017115:Catheter Ablation; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000098:blood supply / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D020913:Perindopril / Q000008:administration & dosage*; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D024482:Vitamin K 2 / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000806:Angiotensin-Converting Enzyme Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D024482:Vitamin K 2; C030814:menatetrenone; D020913:Perindopril