Hepatocellular carcinoma patients with increased oxidative stress levels are prone to recurrence after curative treatment: a prospective case series study using the d-ROM test

  • Yusuke Suzuki
  • Kenji Imai
  • Koji Takai
  • Tatsunori Hanai
  • Hideki Hayashi
  • Takafumi Naiki
  • Yoichi Nishigaki
  • Eiichi Tomita
  • Masahito ShimizuEmail author
  • Hisataka Moriwaki
Original Paper



Oxidative stress plays an important role in liver carcinogenesis. To determine the impact of oxidative stress on the recurrence of stage I/II hepatocellular carcinoma (HCC) after curative treatment, we conducted a prospective case series analysis.


This study included 45 consecutive patients with stage I/II HCC, who underwent curative treatment by surgical resection or radiofrequency ablation at Gifu Municipal Hospital from 2006 to 2007. In these 45 cases, recurrence-free survival was estimated using the Kaplan–Meier method. The factors contributing to HCC recurrence, including the serum levels of derivatives of reactive oxygen metabolites (d-ROM) as an index of oxidative stress, were subjected to univariate and multivariate analyses using the Cox proportional hazards model.


The serum levels of d-ROM (P = 0.0231), α-fetoprotein (AFP, P = 0.0274), and fasting plasma glucose (P = 0.0400) were significantly associated with HCC recurrence in the univariate analysis. Multivariate analysis showed that the serum levels of d-ROM (hazard ratio [HR] 1.0038, 95 % confidence interval [CI] 1.0002–1.0071, P = 0.0392) and AFP (HR 1.0002, 95 % CI 1.0000–1.0003, P = 0.0316) were independent predictors of HCC recurrence. Kaplan–Meier analysis showed that recurrence-free survival was low in patients with high serum d-ROM (≥570 Carr U, P = 0.0036) and serum AFP (≥40 ng/dL, P = 0.0185) levels.


The serum levels of d-ROM and AFP can be used for screening patients with a high risk for HCC recurrence. Patients who show increased levels of these factors require careful surveillance.


Hepatocellular carcinoma Oxidative stress d-ROM Carcinogenesis 



This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan (No. 22790638 to M. S. and No. 21590838 to H. M.) and by Grant-in-Aid for the 3rd Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

432_2013_1389_MOESM1_ESM.pptx (75 kb)
Supplementary material 1 (PPTX 75 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Yusuke Suzuki
    • 1
  • Kenji Imai
    • 2
  • Koji Takai
    • 2
  • Tatsunori Hanai
    • 2
  • Hideki Hayashi
    • 1
  • Takafumi Naiki
    • 2
  • Yoichi Nishigaki
    • 1
  • Eiichi Tomita
    • 1
  • Masahito Shimizu
    • 2
    Email author
  • Hisataka Moriwaki
    • 2
  1. 1.Department of GastroenterologyGifu Municipal HospitalGifuJapan
  2. 2.Department of MedicineGifu University Graduate School of MedicineGifuJapan

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