Reply to: “HCV infection, HOMA index and sustained virological response: The step we need to take before moving forward”
Authors: Pierre Deltenre, Philippe Mathurin, Lawrence Serfaty
Journal: Journal of Hepatology (2012)

HCV infection, HOMA index and sustained virological response: The step we need to take before moving forwardJournal of HepatologyVol. 57Issue 2PreviewWe read with great interest the recent meta-analysis by Deltenre et al. [1]. Authors included 14 studies involving 2732 HCV-positive patients and showed that insulin-resistance (IR) has an evident negative association with the possibility of achieving a sustained virological response (SVR) to Peg-Interferon and ribavirin, in particular in patients with genotype 1 infection. As discussed, some important limitations do not allow an independent association of IR with treatment failure to be highlighted. Full-Text PDF Open AccessImpact of insulin resistance on sustained response in HCV patients treated with pegylated interferon and ribavirin: A meta-analysisJournal of HepatologyVol. 55Issue 6PreviewRecent studies suggested that SVR rates might be lower in HCV patients with insulin resistance (IR) than in patients without IR, but the extent of the impact of IR on treatment response has not been established. We aimed to confirm the role of IR assessed by the homoeostasis model assessment (HOMA-IR) on SVR and to determine its magnitude. Full-Text PDF To the Editor: We thank Dr. La Mura for commenting on our meta-analysis concerning the impact of insulin resistance (IR) on sustained virological response (SVR) in HCV patients treated with pegylated interferon and ribavirin [[1]Deltenre P. Louvet A. Lemoine M. Mourad A. Fartoux L. Moreno C. et al.Impact of insulin resistance on sustained response in HCV patients treated with pegylated interferon and ribavirin: a meta-analysis.J Hepatol. 2011; 55: 1187-1194Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar]. We agree that other predictive factors possibly influencing SVR rates, such as extensive fibrosis, age, level of viremia, IL28B polymorphisms, BMI and steatosis [2Bressler B.L. Guindi M. Tomlinson G. Heathcote J. High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C.Hepatology. 2003; 38: 639-644Crossref PubMed Scopus (334) Google Scholar, 3McHutchison J.G. Lawitz E.J. Shiffman M.L. Muir A.J. Galler G.W. McCone J. et al.Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection.N Engl J Med. 2009; 361: 580-593Crossref PubMed Scopus (1122) Google Scholar, 4Poynard T. Ratziu V. McHutchison J. Manns M. Goodman Z. Zeuzem S. et al.Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C.Hepatology. 2003; 38: 75-85Crossref PubMed Scopus (548) Google Scholar], were not taken into account. Only a meta-analysis of individual data (frequently unfeasible) would be able to address this issue. Despite this, it is likely that IR itself contributes to a reduction in the likelihood of viral eradication, given the magnitude of the reduction in SVR rates in patients with IR (20%), its impact regardless of genotype and absence of heterogeneity. We also agree that overexpression of suppressors of cytokine signaling (SOCS-3) induced by HCV may be one mechanism explaining the non-response to antiviral therapy. The data that Dr. La Mura presented provide additional arguments supporting this explanation. Finally, we agree that, ideally, a dose effect of IR on SVR rates should be explored. However, such an approach is difficult in that it assumes that an accurate easy-to-use tool for assessing the severity of IR is available. Several limitations involved in measuring IR using the HOMA-IR index have recently been pointed out [[5]Lam K.D. Bacchetti P. Abbasi F. Ayala C.E. Loeb S.M. Shah V. et al.Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: impact of obesity and ethnicity.Hepatology. 2010; 52: 38-46Crossref PubMed Scopus (37) Google Scholar], and thus it is not certain that the HOMA-IR index is the ideal tool. In addition, other potential confounding factors again need to be considered, since the magnitude of the impact of IR on SVR may differ according to age, fibrosis, etc. Finally, the distinction between patients with metabolically-related IR and those with HCV-related IR is crucial, since their respective impacts on SVR rates may be different. Therefore, up to now, and despite the limitations discussed above, the HOMA-IR index measured prior to antiviral therapy offers an easy way of identifying insulin-resistant patients who have lower probability of SVR following pegylated bitherapy. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.