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

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 5 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 5 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 5 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.

Long-Term Follow-Up of Chronic Hepatitis C Patients Treated with Interferon-Alpha: Risk of Cirrhosis and Hepatocellular Carcinoma in a Single Center over 10 Years

“…This result is consistent with almost all clinical studies; advanced fibrosis and cirrhosis are the strongest predictors of HCC development [9,27,28,29,30]. The incidence of HCC with CHC and cirrhosis is estimated at 1-4% per year [1,2].…”

“…Also, the recent introduction of direct-acting antiviral agents such as boceprevir and telaprevir has been shown to improve sustained virological response (SVR) by up to 63-75% in treatment-naïve HCV genotype 1 patients [8]. Achievement of SVR after treatment has been associated with improvement in disease progression and liver histology, as well as a reduced risk of HCC and liver-related mortality [9,10,11,12,13]. …”

Hepatitis C virus infection and type 1 and type 2 diabetes mellitus

“…Diabetic HCV-positive patients have increased risk compared with non-diabetic subjects, and DM itself seems to have a selective impact on HCC development [232][233][234][235][236][237][238][239][240][241][242][243][244][245][246][247][248][249][250][251] . The main characteristic of diabetic patients is IR, which plays a crucial role in fibrosis progression and has a negative impact on treatment responses to antiviral therapy in patients with CHC [52,252,253] .…”

Eradication of Hepatitis C Virus Infection and the Development of Hepatocellular Carcinoma

“…As a result, the absolute reduction in risk was 4.6% (CI, 4.2% to 5.0%) for patients achieving an SVR. All of the studies included in the meta-analysis adjusted for age, 9 studies controlled for fibrosis stage (17,27,36,50,51,53,57,58,61), and some studies (46,54) controlled for fibrosis stage with typical markers for advanced fibrosis. One study did not exclude patients with positive hepatitis B serologic test results, but its model was adjusted for the presence of hepatitis B (27).…”