Hung CH, Lee CM, Wang JH, Hu TH, Chen CH, Lin CY, Lu SNImpact of diabetes mellitus on incidence of hepatocellular carcinoma in chronic hepatitis C patients treated with interferon-based antiviral therapy. Int J Cancer 128: 2344-2352

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: 5.09). 05/2011; 128(10):2344-52. DOI: 10.1002/ijc.25585
Source: PubMed


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.

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Available from: Chao-Hung Hung, Aug 20, 2015
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    • "Furthermore, we have compared cytokinomes of LC and CHD patients to realize what molecules were significantly different in these two stages because in literature it has been reported that patients with chronic CHC infection and type 2 diabetes without liver cirrhosis can evolve into hepatocarcinogenesis [8]–[9]. In details, β-NGF is higher in LC patients whereas glucagon and IL-18 are higher in CHD patients (Figure 3). "
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    ABSTRACT: Both type 2 diabetes (T2D) and chronic hepatitis C (CHC) infection are associated with increased risk of developing hepatocellular carcinoma (HCC). Cytokines are known to play an important role not only in the mechanisms of insulin resistance and glucose disposal defects but also in the pathological processes occurring in the liver during viral infection. We evaluated the serum levels of many cytokines, chemokines, adipokines and growth factors in patients with type 2 diabetes, CHC, CHC-related cirrhosis, CHC and type 2 diabetes and CHC-related cirrhosis and type 2 diabetes by BioPlex assay. The obtained data evidenced that the serum levels of some proteins are significantly up-regulated in all the patients or in those with only one disease and are often higher, even if in different amounts, when both diseases are associated. In particular, our results can be useful for the clinical monitoring of patients because they give specific information in regard to the progression from CHC to LC and CHD to LCD. Moreover, some molecules have shown significant correlations with clinical/biochemical data, suggesting the possibility to define mini-panels that can be used as specific markers for the different disease staging. However, our observations demonstrate that an integrated approach is much more powerful than isolated measurements to evaluate specific stages of these two complex pathologies (type 2 diabetes and chronic CHC hepatitis) alone or when they are concomitant in a patient. In fact it has emerged as an accurate, simple, specific, noninvasive, reproducible and less expensive method that, in future, could be included in routine clinical practice to monitor the association of type 2 diabetes and/or CHC to liver cirrhosis and, possibly, to cancer, and to improve the prognosis of these diseases.
    Full-text · Article · Jun 2012 · PLoS ONE
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    • "The cohort ranged in size from 40 [57] to 1,298,385 [61].The duration of follow-up ranged from 2.78 years [21] to 25 years [64] in population-based cohort studies and ranged from 18 months [55] to 7 years [8] in clinic-based cohort studies. Seven studies [18], [19], [21], [26], [55], [66], [68] assessed type II DM only; and an additional 21 studies did not distinguish between type I and type II DM. The characteristics of the included studies are shown in Table S1. "
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    ABSTRACT: The impact of pre-existing diabetes mellitus (DM) on hepatocellular carcinoma (HCC) occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis. We searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models. The database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM) was significantly associated with increased risk of HCC incidence [meta-relative risk (RR) = 1.87, 95% confidence interval (CI): 1.15-2.27] and HCC-specific mortality (meta-RR = 1.88, 95%CI: 1.39-2.55) compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13-1.48) risk of death from all-causes and 91% increased (95%CI: 1.41-2.57) risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12-3.33) compared with non-diabetic patients. The findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes have a poorer prognosis relative to their non-diabetic counterparts.
    Full-text · Article · Dec 2011 · PLoS ONE
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    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.
    No preview · Article · Jan 2011 · Antiviral therapy
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