Diabetes mellitus reduces the therapeutic effectiveness of interferon‐α2b plus ribavirin therapy in patients with chronic hepatitis C

Konishi, Ichiro; Horiike, Norio; Hiasa, Yoichi; Terada, Yoshio; Mashiba, Toshie; Michitaka, Kojiro; Miyake, Yasuyuki; Nonaka, Suguru; Joukou, Kouji; Matsuura, Bunzo; Onji, Morikazu

doi:10.1111/j.1872-034x.2007.00052.x

Cited by 29 publications

(30 citation statements)

References 42 publications

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“…These adipocytokines lead to IFN resistance by blocking STAT phosphorylation. Recent data indicate that the incidence of altered baseline glucose level and the appearance of diabetes type 2 were greater in non-responder cases than in SVR cases [14] . Experimental data obtained by using the replicon model also reported that when insulin levels similar to those seen in patients in a hyperinsulinemic state were added to IFN, the ability to block HCV replication disappeared [15] .…”

Section: Discussionmentioning

confidence: 99%

Predictive Value of the Phosphorylation of Signal Transducers and Activators of Transcription in the Outcome of Interferon Therapy for Chronic Hepatitis C

Miyaaki

Ichikawa²,

Nakao³

et al. 2008

Intervirology

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Objective: Signal transducers and activators of transcription (STATs) play a critical role in antiviral defense. To better understand pegylated interferon (IFN)-α and ribavirin combination therapy resistance, we examined the STAT expression in the liver. Methods: We immunostained Phospho-STAT1 (P-STAT1) and Phospho-STAT3 (P-STAT3) in 59 hepatitis C virus (HCV)-infected liver tissues and compared the expression of these STATs proteins and the clinicopathological factors. Results: The number of P-STAT1 observed correlated significantly with the body mass index (BMI; p = 0.03) and homeostatic model assessment (p = 0.007). The number of P-STAT3 observed correlated significantly with the ALT level (p = 0.002) and platelet count (p = 0.002). The number of P-STAT1 nuclei in the sustained virological response (SVR) group was significantly larger than in the non-SVR group (p = 0.003). On multivariance analysis, the number of P-STAT1 nuclei (p = 0.004) and age (p = 0.016) were significant predictors of SVR. Conclusions: P-STAT1 in the liver tissue prior to IFN therapy correlated with an increased BMI and increased insulin resistance, and might be a useful predictor of HCV clearance by IFN therapy. On the other hand, P-STAT3 might play a critical role in the hepatocellular response against inflammatory damage.

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Section: Discussionmentioning

confidence: 99%

Predictive Value of the Phosphorylation of Signal Transducers and Activators of Transcription in the Outcome of Interferon Therapy for Chronic Hepatitis C

Miyaaki

Ichikawa²,

Nakao³

et al. 2008

Intervirology

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“…While knowledge of disease and treatment outcome in diabetic HCV patients will have wide clinical applicability, those patients have historically been excluded from clinical trials. There is, however, early evidence of a central role for insulin resistance (IR), a fundamental finding in type 2 DM, in failure to achieve SVR in HCV patients [12][13][14][15][16][17][18]. In a prospective study of Spanish patients with chronic hepatitis C (CHC) [16], SVR was only 32.8% in HCV genotype 1 patients with IR (defined by the homeostasis model of assessment, HOMA-IR [ 2) compared to an SVR rate of 60.5% in those with without IR (HOMA-IR B 2).…”

Section: Introductionmentioning

confidence: 99%

Diabetes Mellitus Is Associated with Impaired Response to Antiviral Therapy in Chronic Hepatitis C Infection

et al. 2009

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Compared to HCV non-diabetics, HCV diabetics were more likely to have steatosis (P<0.0001) and advanced fibrosis (P=0.003). Patients' age, Caucasian ethnicity, obesity, and histologic activity index were independently associated with advanced fibrosis (P<0.05). Only 23% of HCV diabetics achieved SVR compared to 46% of HCV non-diabetics (P=0.003). DM, genotype 1, high baseline viral load, and African- American ethnicity were independently associated with less SVR (P<0.05). Significant adverse events were more common in HCV diabetics compared to HCV non-diabetics (P=0.001). Side effects did not increase in patients receiving PEG IFN/RBV and insulin sensitizers. Conclusion DM was associated with impaired virologic response to PEG IFN/RBV in HCV patients. Adverse events during therapy were more frequent in diabetic compared to non-diabetic HCV patients.

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“…Indeed, identifying patients who are at risk of developing diabetes, and have CHC, reduces liver disturbance progression [267,268] , the incidence of HCC and transplant-related morbidity and mortality. Additionally, this identification improves the response to antiviral therapy [269][270][271] , even reducing the side effects of the treatment [270] by encouraging the pretreatment of IR and DM [265] . Moreover, clinical trials on HCV-positive patients have reported improvement in glucose metabolism after antiviral treatment [187] .…”

Section: Prevention and Treatmentmentioning

confidence: 99%

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

Antonelli

Ferrari

Giuggioli

et al. 2014

WJD

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cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients. AbstractHepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory Submit a

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Diabetes mellitus reduces the therapeutic effectiveness of interferon‐α2b plus ribavirin therapy in patients with chronic hepatitis C

Abstract: The findings indicate that DM reduces the response to IFN-alpha2b plus ribavirin therapy in CHC patients.

Cited by 29 publications

References 42 publications

Predictive Value of the Phosphorylation of Signal Transducers and Activators of Transcription in the Outcome of Interferon Therapy for Chronic Hepatitis C

Predictive Value of the Phosphorylation of Signal Transducers and Activators of Transcription in the Outcome of Interferon Therapy for Chronic Hepatitis C

Diabetes Mellitus Is Associated with Impaired Response to Antiviral Therapy in Chronic Hepatitis C Infection

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

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