HCV infection, HOMA index and sustained virological response: The step we need to take before moving forward
Authors: Vincenzo La Mura, Marcello Persico
Journal: Journal of Hepatology (2012)

We read with great interest the recent meta-analysis by Deltenre et al. [[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 (74) Google Scholar]. 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. Other predictive factors, genetic and non-genetic, could be behind this association such as IL-28 polymorphism, fibrosis, age, viremia, presence of steatosis and other clinical variables associated with the metabolic syndrome. Hence, a real cause-effect relation is still an open question, and a sort of “dose effect” of IR on SVR has never been exhaustively explored. We believe that investigations aimed at solving these issues are a priority area of research in order to optimize the management of HCV patients. In accordance with the results by Walsh et al. [[2]Walsh M.J. Jonsson J.R. Richardson M.M. Lipka G.M. Purdie D.M. Clouston A.D. et al.Non-response to antiviral therapy is associated with obesity and increased hepatic expression of suppressor of cytokine signalling 3 (SOCS-3) in patients with chronic hepatitis C, viral genotype 1.Gut. 2006; 55: 529-535Crossref PubMed Scopus (262) Google Scholar], authors argued the overexpression of suppressor of cytokine signaling (SOCS-3) induced by HCV as one of the mechanisms evoked to explain the association of the metabolic syndrome with non-response to antiviral therapy. However, they consider this observation as never confirmed by other studies. Nevertheless, we wish to point out that Huang et al. [[3]Huang Y. Feld J.J. Sapp R.K. Nanda S. Lin J.H. Blatt L.M. et al.Defective hepatic response to interferon and activation of suppressor of cytokine signaling 3 in chronic hepatitis C.Gastroenterology. 2007; 132: 733-744Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar] and our personal data [[4]Persico M. Capasso M. Persico E. Svelto M. Russo R. Spano D. et al.Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus-related chronic hepatitis: insulin resistance and response to antiviral therapy.Hepatology. 2007; 46: 1009-1015Crossref PubMed Scopus (145) Google Scholar] have confirmed the overexpression of SOCS-3 in the liver of non-responders to antiviral therapy. Moreover, in vitro data by our group suggested that this is dependent on the genotype, giving an indirect clue that, if an interference of HCV with insulin signaling exists, it could be mainly due to genotype 1 infection [[5]Persico M. Russo R. Persico E. Svelto M. Spano D. Andolfo I. et al.SOCS3 and IRS-1 gene expression differs between genotype 1 and genotype 2 hepatitis C virus-infected HepG2 cells.Clin Chem Lab Med. 2009; 47: 1217-1225Crossref PubMed Scopus (19) Google Scholar], but the debate is still open [[6]Pazienza V. Clément S. Pugnale P. Conzelman S. Foti M. Mangia A. et al.The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms.Hepatology. 2007; 45: 1164-1171Crossref PubMed Scopus (200) Google Scholar]. Deltenre et al. also stated that the HOMA-IR index measured prior to antiviral therapy could be useful to implement a potential combined score at basal evaluation to predict treatment response. We totally agree with this statement but we probably need to take a step before moving forward. The individual value of HOMA-IR index has been largely discussed [[7]Wallace T.M. Levy J.C. Matthews D.R. Use and abuse of HOMA modeling.Diabetes Care. 2004; 27: 1487-1495Crossref PubMed Scopus (3214) Google Scholar]. Exploring the possibility of a dose effect of IR on SVR is probably the first step to take as a reliable cut-off to define the presence of IR by HOMA does not exist, neither the reproducibility of a specific cut-off in patients with or without clinical features of metabolic syndrome has ever been explored. All these aspects, presently, do not allow taking a step forward in terms of further predicting SVR in HCV patients by using the HOMA-IR index. The higher the accuracy of the predictive system, the higher the optimization of HCV treatment and the development of new antiviral drugs make it imperative. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. Impact 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 Reply to: “HCV infection, HOMA index and sustained virological response: The step we need to take before moving forward”Journal of HepatologyVol. 57Issue 2PreviewTo the Editor: Full-Text PDF Open Access