Effect of sustained virological response to treatment on the incidence of abnormal glucose values in chronic hepatitis C☆
Introduction
The development of type 2 diabetes mellitus depends on environmental, genetic and diet-related factors. Data supporting a link between hepatitis C infection, insulin resistance and type 2 diabetes mellitus [1] include: (1) insulin resistance is higher in chronic hepatitis C than in other chronic liver diseases, despite the same fibrosis stage, body mass index, age and family history of diabetes [2]; (2) in transgenic mice, the expression of HCV core protein is associated with insulin resistance, following a fat-enriched diet, and with type 2 diabetes development [3]; (3) clearance of the virus following successful treatment is related to a fall in the insulin resistance index measured by the homeostasis model of assessment (HOMA) [4]; (4) cross-sectional studies have found higher prevalence of diabetes mellitus in patients with chronic hepatitis C than in healthy subjects, or in those suffering from other chronic liver diseases [5]; (5) case-cohort studies have demonstrated a higher incidence of type 2 diabetes mellitus during follow-up in patients with hepatitis C, as compared to non-infected subjects [6]. The mechanisms by which hepatitis C impairs insulin sensitivity and promotes diabetes include: increased tumour necrosis factor (TNF-α) production [7] and over-expression of suppressor of cytokines signal 3 (SOCS-3) [8] which have been shown to interfere with the intracellular signalling pathway of insulin.
The main aim of the current study was to assess the effect of sustained virological response, together with host and viral factors, on the incidence of impaired fasting glucose and/or type 2 diabetes mellitus in patients with chronic hepatitis C being treated with combined interferon plus ribavirin. Further, we sought to assess the impact of baseline glucose status on sustained virological response rate.
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Patient population
Patients from 11 Spanish hospitals were recruited and treated according to routine clinical practice. Patients (n = 1059; male = 649 (61.2%) and females = 410 (38.8%); mean age = 48 ± 11 years, range = 20–75) with biopsy-proven chronic hepatitis C and HCV RNA positive were recruited. They were receiving treatment with combination therapy of standard interferon plus ribavirin (n = 183), or peginterferon alfa-2a plus ribavirin (n = 501), or peginterferon alfa-2b plus ribavirin (n = 368). Viral genotype
Factors associated with sustained virological response
Patients with SVR were younger (46.2 ± 10.4 vs. 50.4 ± 10.4 years; P < 0.001), had lower glucose concentrations (5.4 ± 1.31 mmol/L vs. 5.75 ± 1.58 mmol/L; P < 0.001), lower baseline HCV RNA load (5.74 ± 0.6 log10 vs. 5.88 ± 0.49log10; P < 0.05), lower triglyceride concentrations (1.05 ± 0.66 mmol/L vs. 1.14 ± 0.79 mmol/L; P < 0.05), and higher total cholesterol concentrations (4.48 ± 1.0 mmol/L vs. 4.31 ± 0.96 mmol/L, P < 0.005). There were no significant associations with gender, body mass index, and levels of ALT, AST or
Discussion
Our results showed that the eradication of hepatitis C virus reduced by half the incidence of type 2 diabetes and/or impaired fasting glucose in the course of post-treatment follow-up. Further, sustained response and fibrosis stage were the variables that were independently predictive of the development of abnormal glucose concentrations. The significance was maintained even when analysed together with variables that are known to be strongly related to the risk of developing diabetes such as
Acknowledgement
We thank Dr. Peter Turner for Editorial assistance.
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The authors who have taken part in the research of this paper declared that they do not have a relationship with the manufacturers of the drug involved either in the past or present and they did not receive funding from the manufacturers to carry out their research. They did not receive funding from any source to carry out this study.