Sustained virological response reduces incidence of onset of type 2 diabetes in chronic hepatitis C†

Abstract

Diabetes is present in patients with chronic hepatitis C virus infection. The aim of this retrospective cohort study was to assess the cumulative development incidence and predictive factors for type 2 diabetes after the termination of interferon therapy in Japanese patients positive for hepatitis C virus (HCV). A total of 2,842 HCV-positive patients treated with interferon (IFN) monotherapy or combination therapy with IFN and ribavirin were enrolled. The mean observation period was 6.4 years. An overnight (12-hour) fasting blood sample or a casual blood sample was taken for routine analyses during follow-up. The primary goal was the onset of type 2 diabetes. Evaluation was performed by using the Kaplan-Meier method and Cox proportional hazard analysis. Of 2,842 HCV patients, 143 patients developed type 2 diabetes. The cumulative development rate of type 2 diabetes was 3.6% at 5 years, 8.0% at 10 years, and 17.0% at 15 years. Multivariate Cox proportional hazard analysis revealed that type 2 diabetes development after the termination of IFN therapy occurred when histological staging was advanced (hazard ratio 3.30; 95% confidence interval [CI] 2.06-5.28; P < 0.001), sustained virological response was not achieved (hazard ratio 2.73; 95% CI 1.77-4.20; P < 0.001), the patient had pre-diabetes (hazard ratio 2.19; 95% CI 1.43-3.37; P < 0.001), and age was >50 years (hazard ratio 2.10; 95% CI 1.38-3.18; P < 0.001). H epatitis C virus (HCV) is one of the more common causes of chronic liver disease in world. Chronic hepatitis C is an insidiously progressive form of liver disease that relentlessly but silently progresses to cirrhosis in 20% to 50% of cases over a period of 10 to 30 years. [1][2][3] In addition, HCV is a major risk for hepatocellular carcinoma (HCC). 4-8 Moreover, chronic HCV infection has been associated with a variety of extrahepatic complications such as essential mixed cryoglobulinemia, porphyria cutanea tarda, membranoproliferative glomerulonephritis, autoimmune thyroiditis, sialadenitis, and cardiomyopathy. [9][10][11][12][13] Lately, data supporting a link between type 2 diabetes mellitus (T2DM) and chronic hepatitis C infection have been reported. 14,15 Although there is growing evidence to support the concept that HCV infection is a risk factor for developing T2DM, there have been a few interventional studies confirming this issue. This issue needs to be confirmed with a long-term follow-up of patients with high risk of developing diabetes. Thus, prospective studies including metabolic evaluations are clearly needed to clarify these issues.With this background in mind, the cohort study was initiated to investigate the cumulative incidence and risk factors of T2DM after prolonged follow-up in HCV-infected patients treated with interferon (IFN) monotherapy or combination therapy with IFN and ribavirin. The strengths of the current study are the large numbers of patients included and the long-term follow-up of patients. Patients and MethodsPatients. There were 5,890 patients diagnosed with chronic ...

Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial

“…32,33 Given the effect of IR on fibrosis progression and risk of hepatocellular carcinoma, there is a rationale for reducing IR in patients with chronic hepatitis C. SVR has been associated with reduced risk of glucose metabolism disturbances during posttreatment follow-up. 2,3 Therefore, one of the best approaches to managing IR is to eradicate HCV infection. However, as discussed above, patients with IR are less likely to respond to peginterferon/ribavirin.…”

“…2,3 Proposed mechanisms for HCV-related IR and diabetes mellitus include direct hepatic effects [4][5][6] and potential contributions from extrahepatic organs. 7,8 In HCV-infected patients, IR appears to influence disease progression and response to treatment with peginterferon alpha and ribavirin.…”

Impact of Weight Loss in Overweight Patients Enrolled in Weight Management Program Prior to Hepatitis C Treatment on Early Virological Response

“…The mechanisms of the impact of obesity and potential beneficial role of weight loss on response to IFN bases CRC therapy have not been clearly defined. Possible mechanisms include the effect on hepatic steatosis [25][26][27][28][29][30], insulin resistance and altered immune response. Weight management has been shown not only to a decrease in steatosis but also improvement in fibrosis severity [25,26].…”

Successful Hepatitis C Antiviral Therapy Induces Remission of Type 2 Diabetes: A Case Report

“…Several observational studies have demonstrated that successful treatment of HCV with IFN/Ribavirin leads to improved insulin sensitivity and may reduce the long-term risk of type 2 diabetes [10,[13][14][15]. Tahrani et al reported a case of improved glycemic control and hypoglycemic episodes requiring cessation of diabetes therapies during treatment with IFNaRibavirin (Table 2) [16].…”

“…Several observational studies have demonstrated that eradication of HCV is associated with improved insulin sensitivity and may reduce the long-term risk of diabetes in this population [13][14][15]. Case reports have described improvements in glycemic control with treatment of HCV with both IFN/Ribavirin and IFN/Ribavirin/telaprevir; however, the improvements were limited to the treatment phase [16,17].…”