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 5 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 3 year) was ! 20, and T2DM was present. T2DM caused a 1.70-fold enhancement in the development of malignancies other than HCC. Conclusion: 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. (HEPATOLOGY 2013;57:964-973)

Cost-Outcome Description of PEG-IFN-α2b+RBV for Hepatitis C: Results Based on the Interferon Database

“…Utilities are described by Quality Adjusted Life Year (QALY). QALYs and transition probabilities are similar to previous HCV treatment economic evaluation studies in Japan [15][16][17][18][19][20][21][22] (Tables 1, 2). The simulation was performed using the Tree Age Pro Healthcare 2016 v2.1 (Tree Age Software, Inc., Williamstown, MA, U.S.A.) for a period of 10 years with no discount rate.…”

“…The simulation was performed using the Tree Age Pro Healthcare 2016 v2.1 (Tree Age Software, Inc., Williamstown, MA, U.S.A.) for a period of 10 years with no discount rate. 15) CH to HCC 0.016 Nakamura et al 15) comp-LC to decomp-LC 0.021 Imazeki et al 16) comp-LC to HCC 0.043 Hayashida et al 17) decomp-LC to HCC 0.083 Nakamura et al 15) decomp-LC to death 0.153 Nakamura et al 15) HCC to death 0.200 Nakamura et al 15) comp-LC SVR to HCC 0.018 Arase et al 18) CH/comp-LC to SVR 0.080 Broglio et al 19) …”

A single-amino-acid mutation in hepatitis C virus NS5A disrupts physical and functional interaction with the transcription factor HNF-1α

“…Clinical and experimental studies suggest that HCV is an additional risk factor for the development of diabetes (Mason et al, 1999;Mehta et al, 2003;Negro, 2011;Negro & Alaei, 2009). Moreover, type 2 diabetes increases the risk for the development of HCC in HCV-infected patients (Arase et al, 2013;Lai et al, 2012;Wang et al, 2012).…”

APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing

“…Nevertheless, SVR patients remain at risk of HCC development, especially those with old age, high baseline gamma-glutamyltransferase levels, advanced liver fibrosis or comorbidity such as diabetes [206][207][208]. High APRI 6 months after the end of treatment [209] and high posttreatment ALT or AFP levels [210] were independent factors significantly associated with HCC development.…”