Response to Lecube et al.
We read with great interest the review article by Lecube et al. (1) on the pathogenic factors specifically linking hepatitis C virus (HCV) infection and glucose abnormalities. After analyzing the different mechanisms by which HCV is thought to contribute to the development of type 2 diabetes, Lecube et al. focus their attention on the role of proinflammatory cytokines, in particular tumor necrosis factor (TNF)-α and interleukin-6. They suggest that the activation of the TNF-α system in HCV-infected patients, which has been directly related to insulin resistance in their recent study (2), could be related to the T-helper (Th)1 immune response observed in the course of HCV infection. Accordingly, as shown in Fig. 1 of their review article, the activation of the TNF-α system following the Th1 immune-mediated response is central to the pathogenesis of both liver fibrosis and insulin resistance associated with HCV infection.
However, an apparent paradox is raised by an attempt to fit such interpretation with well-acquired data and the most recent evidence from literature. Indeed, a vigorous Th1 cytokine response has been classically observed in patients who clear their HCV infection, either spontaneously (3) or in response to antiviral treatment (4,5). By contrast, recent studies have demonstrated that insulin resistance is independently associated with a poor response to antiviral therapy in HCV patients (6,7), consistent with previous observations on the lower success rate of interferon alone or interferon plus ribavirin in obese and diabetic patients. Therefore, it is difficult to understand how an increased Th1 immune response, which is protective in relation to viral clearance, can be, at the same time, the major determinant of insulin resistance and responsible for a poor response to antiviral treatment.
Footnotes
- DIABETES CARE