Effect of type 2 diabetes on risk for malignancies includes hepatocellular carcinoma in chronic hepatitis C

Department of Health Management Center, Toranomon Hospital, Tokyo, Japan
Hepatology (Impact Factor: 11.06). 03/2013; 57(3). DOI: 10.1002/hep.26087
Source: PubMed


The aim of this retrospective cohort study was to assess the cumulative development incidence and predictive factors for malignancies after the termination of interferon (IFN) therapy in Japanese patients for hepatitis C virus (HCV). A total of 4,302 HCV-positive patients treated with IFN were enrolled. The mean observation period was 8.1 years. The primary outcome was the first onset of malignancies. Evaluation was performed using the Kaplan-Meier method and Cox proportional hazard analysis. A total of 606 patients developed malignancies: 393 developed hepatocellular carcinoma (HCC) and 213 developed malignancies other than HCC. The cumulative development rate of HCC was 4.3% at 5 years, 10.5% at 10 years, and 19.7% at 15 years. HCC occurred significantly (P<0.05) when the following characteristics were present: advanced histological staging, sustained virological response not achieved, male sex, advanced age of ≥50 years, total alcohol intake of ≥200 kg, and presence of type 2 diabetes (T2DM). T2DM caused a 1.73-fold enhancement in HCC development. In patients with T2DM, HCC decreased when patients had a mean hemoglobin A1c (HbA1c) level of <7.0% during follow-up (hazard ratio, 0.56; 95% confidence interval, 0.33-0.89; P=0.015). The cumulative development rate of malignancy other than HCC was 2.4% at 5 years, 5.1% at 10 years, and 9.8% at 15 years. Malignancies other than HCC occurred significantly when patients were of advanced age of ≤50 years, smoking index (package per day×year) was ≥20, and T2DM was present. T2DM caused a 1.70-fold enhancement in the development of malignancies other than HCC.

T2DM causes an approximately 1.7-fold enhancement in the development of HCC and malignancies other than HCC in HCV-positive patients treated with IFN. In T2DM patients, maintaining a mean HbA1c level of <7.0% reduces the development of HCC.

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    • "In addition, HCV is a major risk for hepatocellular carcinoma (HCC) [Hasan et al., 1990; Kew et al., 1990; Ikeda et al., 1993; Tsukuma et al., 1993; Arase et al., 2012]. In addition, several authors have reported that HCV clearance decreases the rate of fibrosis progression and the development of HCC in patients with chronic HCV infection [Kasahara et al., 1998; Yoshida et al., 2002; Arase et al., 2013]. On the other hand, hemorrhagic stroke is a medical emergency and can cause permanent neurological damage and death [Truelsen et al., 2003; Iso et al., 2007; Donnan et al., 2008]. "
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    ABSTRACT: The aim of this retrospective cohort study was to assess the cumulative incidence and predictive factors for intracerebral hemorrhagic stroke after the termination of interferon (IFN) therapy in Japanese patients with hepatitis C virus (HCV). A total of 4,649 HCV-positive patients treated with IFN were enrolled. The primary goal is the first onset of intracerebral hemorrhagic stroke. The mean observation period was 8.0 years. Evaluation was performed using the Kaplan-Meier method and the Cox proportional hazard model. A P-value of less than 0.05 was considered statistically significant. A total of 28 developed intracerebral hemorrhagic stroke. The cumulative incidence of intracerebral hemorrhagic stroke was 0.3% at 5 years, 0.8% at 10 years, and 1.7% at 15 years. Intracerebral hemorrhagic stroke occurred when patients had age increments of 10 years (hazard ratio: 2.77; 95% confidence interval (CI) 1.48-5.18; P = 0.001), hypertension (hazard ratio: 2.30; 95% CI 1.09-4.83; P = 0.021), liver cirrhosis (hazard ratio: 4.50; 95% CI 2.07-9.78; P < 0.001), and HCV non-clearance (hazard ratio: 3.22; 95% CI 1.22-8.53; P = 0.018). On the intracerebral hemorrhagic stroke based on the difference of liver fibrosis and efficacy of IFN therapy, HCV clearance reduced to 24.3% (1/4.11) compared to HCV non-clearance in cirrhotic patients (P = 0.040). In conclusion, HCV clearance reduced the development of intracerebral hemorrhagic stroke. In particular, HCV clearance reduced intracerebral hemorrhagic stroke to about one-fourth in cirrhotic patients. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
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    ABSTRACT: Description: The Centers for Disease Control and Prevention (CDC) and a group of governmental and private sector partners developed these evidence-based recommendations to increase the proportion of hepatitis C virus (HCV)-infected persons who know their status and are linked to appropriate care and treatment. The recommendations also address brief alcohol screening, as alcohol accelerates progression of liver disease among HCV-infected individuals. These recommendations augment CDC's 1998 and 1999 recommendations based on risk and medical indications and are not meant to replace those recommendations. Methods: These recommendations are based on systematic reviews of evidence published from 1995 through February 2012 in MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, Sociological Abstracts, and Database of Abstracts of Reviews of Effects. Selected studies included cross-sectional and cohort studies that addressed either prevalence of hepatitis C in the United States or clinical outcomes (for example, hepatocellular carcinoma and serious adverse events) among treated patients and systematic reviews of trials that assessed effectiveness of brief screening interventions for alcohol consumption. The Grading of Recommendations Assessment, Development, and Evaluation framework was used to assess quality of the evidence. RECOMMENDATION 1: Adults born during 1945-1965 should receive 1-time testing for HCV without prior ascertainment of HCV risk. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: All persons with identified HCV infection should receive a brief alcohol screening and intervention as clinically indicated, followed by referral to appropriate care and treatment services for HCV infection and related conditions (Grade: strong recommendation; moderate-quality evidence).
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