We did appreciate the formidable effort by Drs. Sheikh, Sanyal, and colleagues to provide a succinct and yet complete overview of the molecular mechansims involved in the development of insulin resistance in those with hepatitis C virus (HCV) infection.1 The reading of this article raises two major comments.
First, the authors correctly point out HCV to be now viewed “to cause a metabolic syndrome”. Indeed it is not the same metabolic syndrome (MS) as seen in HCV-negative individuals encompassing insulin resistance associated with altered body fat distribution, arterial hypertension, and disturbed glucose and lipid metabolism. In particular, although data are still preliminary, it would appear HCV features a specific HCV-associated dysmetabolic syndrome (HCADS) consisting of the triad of insulin resistance, hypocholesterolemia, and hepatic steatosis.2 At variance with the “true” MS, HCADS might therefore not feature obesity, atherogenic dyslipidemia, and arterial hypertension.2
The second comment, also strictly connected to the former, is that insufficient information is so far available on whether HCADS follows the same course as the MS. For instance, available data appear to support the theory that, similar to the true MS, HCADS is also associated with hepatic steatosis3, 4 and an increased risk of developing type 2 diabetes.5 However, literature data on the risk of premature atherosclerosis in those individuals with HCADS are scant, somewhat contradictory, and more important, available studies are not comparable in terms of experimental design and population studied,2 so that this question remains open.
While basic research discloses exciting new therapeutic strategies against HCV infection, clinical observations may well provide additional clues to highlight similarities and differences between the MS and HCADS. Such clinical observations may, in turn, indicate or contraindicate the use of drugs such as hydroxymethyl-glutaryl-coenzyme A inhibitors (statins). Statins, as the most popular cholesterol-lowering agents, are widely used in the MS and display in vitro anti-HCV properties.6 However, results from an in vivo pilot study with atorvastatin have been disappointing.7 Moreover, statins are familiar to the diabetologist but perhaps may still raise concern among those caring for (HCV) liver patients.8
In conclusion, we feel the combined efforts of the basic scientist together with clinical judgement will result in the generation of new ideas eventually conducive to the altered natural course of HCV infection, not only from a virological, but also from a metabolic point of view.