Diabetes Enhances Hepatocarcinogenesis in Noncirrhotic, Interferon-treated Hepatitis C Patients

American Journal of Medicine
Volume 123, Issue 10, Pages 951-956.e1 (October 2010)

Yusuke Kawamura, MD, Yasuji Arase, MD, Kenji Ikeda, MD, Miharu Hirakawa, MD, Tetsuya Hosaka, MD, Masahiro Kobayashi, MD, Satoshi Saitoh, MD, Hiromi Yatsuji, MD, Hitomi Sezaki, MD, Norio Akuta, MD, Fumitaka Suzuki, MD, Yoshiyuki Suzuki, MD, Hiromitsu Kumada, MD

Abstract

Background
This retrospective cohort study assessed the impact of diabetes mellitus on hepatocarcinogenesis and determined the predictors of hepatocarcinogenesis in noncirrhotic, interferon-treated patients with hepatitis C virus infection.

Methods
A total of 2058 hepatitis C virus-positive, noncirrhotic patients treated with interferon were enrolled. The median follow-up period was 6.7 years. The primary end point was the onset of hepatocellular carcinoma. The cumulative rate of new hepatocellular carcinoma cases was computed by the Kaplan–Meier method and Cox proportional hazard analysis according to diabetic state and response to interferon therapy.

Results
The cumulative rates of hepatocellular carcinoma in diabetic patients (3.2% at 4 years, 8.5% at 8 years, and 24.4% at 12 years) were significantly higher than those of nondiabetic patients (1.3% at 4 years, 2.2% at 8 years, and 5.6% at 12 years, P<.001). In patients with a sustained virologic response, diabetes had no significant effect on the rate of hepatocarcinogenesis. In contrast, the rate in patients with a nonsustained virologic response was significantly higher in diabetic than in nondiabetic patients. Multivariate analysis identified lack of sustained virologic response (hazard ratio [HR] 7.28; 95% confidence interval [CI], 3.28-16.15; P<.001) and diabetes as independent risk factors for hepatocarcinogenesis (HR 2.00; 95% CI, 1.05-3.84; P=.036).

Conclusions
Our results highlight the enhancing effect of diabetes mellitus on hepatocarcinogenesis in noncirrhotic, interferon-treated patients with hepatitis C virus. The sustained virologic response induced by interferon therapy eliminates the influence of diabetes and markedly reduces the rate of hepatocarcinogenesis in such patients.

Keywords: Diabetes, Hepatocellular carcinoma, Interferon, Sustained virologic response

Department of Hepatology, Toranomon Hospital, Tokyo, Japan

Requests for reprints should be addressed to Yusuke Kawamura, MD, Department of Hepatology, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo 105-8470, Japan

Funding: Okinaka Memorial Institute for Medical Research and Japanese Ministry of Health, Labour and Welfare.

Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript.


Authorship: All authors had access to the data and played a role in writing this manuscript.

PII: S0002-9343(10)00468-7
doi:10.1016/j.amjmed.2010.05.013
© 2010 Elsevier Inc. All rights reserved

Source