Article

Impact of diabetes mellitus on incidence of hepatocellular carcinoma in chronic hepatitis C patients treated with interferon-based antiviral therapy

Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan.
International Journal of Cancer (Impact Factor: 5.01). 05/2011; 128(10):2344-52. DOI: 10.1002/ijc.25585
Source: PubMed

ABSTRACT There is strong evidence linking chronic hepatitis C virus (HCV) infection and Type 2 diabetes mellitus (DM). Recent studies have suggested that DM is associated with increased risk of developing hepatocellular carcinoma (HCC). The aim of our cohort study was to assess whether DM influence the incidence of HCC in chronic hepatitis C patients treated with interferon (IFN)-based antiviral therapy. A total of 1,470 chronic hepatitis C patients treated with IFN or pegylated-IFN plus ribavirin therapy were enrolled. Of them, 253 (17%) patients had DM at entry. Evaluation of HCC incidence was performed by Kaplan-Meier method and Cox proportional hazards analysis. Patients with baseline DM were significantly older and had higher body mass index, serum transaminase levels and fibrosis scores and lower platelet counts compared to non-DM subjects. Sustained virological response (SVR) was achieved in 160 (63%) of DM and 867 (71%) of non-DM patients (p = 0.008). During a median follow-up period of 4.3 years, HCC developed in 21 (8.3%) of DM and 66 (5.4%) of non-DM patients (p = 0.017). However, DM was not an independent covariate by Cox proportional hazards analysis. In a subgroup analysis, DM (hazard ratio, 4.32; 95% confidence interval, 1.23-15.25; p = 0.023) was an independent predictor of HCC in the SVR patients without baseline cirrhosis, despite a low HCC incidence. In conclusion, DM has a selective impact on HCC development among chronic hepatitis C patients after IFN-based therapy. DM may increase the HCC risk in chronic hepatitis C without cirrhosis after eradication of HCV.

0 Followers
 · 
105 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies have indicated that interferon (IFN) or pegylated interferon (PEG-IFN) plus ribavirin therapy can achieve sustained virological response (SVR) against HCV equally in dual HBV-HCV infection and in HCV monoinfection. Whether these therapies can reduce hepatocellular carcinoma (HCC) development in dual HBV-HCV infection remains unclear. A total of 135 dually-infected patients with active hepatitis C receiving IFN or PEG-IFN plus ribavirin therapy were enrolled. The cumulative incidence of HCC was compared to that in 1,470 HCV-monoinfected patients. Based on the Cox proportional hazards model, dual infection was an independent factor for HCC development in all 1,605 chronic hepatitis C patients with or without positive hepatitis B surface antigen receiving IFN or PEG-IFN plus ribavirin (hazard ratio (HR)=1.864, 95% CI 1.052-3.303; P=0.033). In dually-infected patients, HCC developed in 4 of 96 with HCV SVR and 11 of 39 without HCV SVR (P < 0.001) after a median follow-up of 4.6 years. Age (HR=1.175, 95% CI 1.070-1.291; P=0.001) and non-HCV-SVR (HR=7.874, 95% CI 2.375-26.32; P=0.001) were independent factors for HCC development. Subgroup analysis showed that HCC occurrence was lower in patients with HCV SVR and HBV DNA levels < 2,000 IU/ml at the end of treatment or follow-up compared to those with HCV SVR and HBV DNA levels ≥ 2,000 IU/ml (P=0.034) and those without HCV SVR (P<0.001). Sustained HCV clearance by IFN or PEG-IFN plus ribavirin therapy may significantly reduce HCC in HBV-HCV dually-infected patients, whereas persistence or reactivation of HBV decreases the benefit of HCV SVR.
    Antiviral therapy 01/2011; 16(7):959-68. DOI:10.3851/IMP1842 · 3.14 Impact Factor
  • Source
    Mediterranean Journal of Hematology and Infectious Diseases 01/2011; 3(1):e2011050. DOI:10.4084/MJHID.2011.050
  • [Show abstract] [Hide abstract]
    ABSTRACT: It is now widely recognized that chronic hepatitis C is a metabolic disease, strongly associated with Type 2 diabetic mellitus and insulin resistance (IR). Chronic hepatitis C virus (HCV) infection promotes IR mainly through interfering with the insulin signaling pathway in hepatocytes, increasing the inflammatory response with production of cytokines such as TNF-α and IL-6, and increasing oxidative stress. Accumulated evidence indicates that HCV-associated IR may lead to fibrosis progression, resistance to antiviral therapy, hepatocarcinogenesis and extrahepatic manifestations. Thus, HCV-associated IR is a therapeutic target at any stage of HCV infection. However, specific pharmaceutical treatments of IR are still being evaluated in clinical trials, but available data do not warrant their use in all chronic hepatitis C patients with IR.
    Expert Review of Anticancer Therapy 05/2011; 9(5):525-33. DOI:10.1586/eri.11.33 · 3.06 Impact Factor
Show more

Preview

Download
1 Download