title: Effect of type 2 diabetes on risk for malignancies includes hepatocellular carcinoma in chronic hepatitis C.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatology and Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan. es9y-ars@asahi-net.or.jp
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saito
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007372:Interferons / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000453:epidemiology; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D007372:Interferons