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

[Guest guest]

http://www.amjmed.com/article/PIIS0002934310004687/abstract?rss=yes

THE AMERICAN JOURNAL OF MEDICINE

Volume 123, Issue 10, Pages 951-956.e1 (October 2010)

Diabetes Enhances Hepatocarcinogenesis in Noncirrhotic, Interferon-treated

Hepatitis C Patients

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

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

---

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.

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.