Reply to “Association between IL28B polymorphism and treatment response in patients with genotype 4 chronic hepatitis C”
Authors: Emilie Estrabaud, Olivier Lada, Tarik Asselah
Journal: Journal of Hepatology (2012)

IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis CJournal of HepatologyVol. 56Issue 3PreviewPolymorphisms in the region of the interleukin (IL)28B gene have been associated with pegylated-interferon (PEG-IFN) and ribavirin treatment response mainly in genotype 1 HCV infections. However, there are few data on HCV genotype 4 (HCV-4) infection. We evaluated, in a unique well-characterized cohort of HCV-4 patients, the association of IL28B polymorphism with response to treatment or liver disease severity. Full-Text PDF Association between IL28B polymorphism and treatment response in patients with genotype 4 chronic hepatitis CJournal of HepatologyVol. 57Issue 3PreviewWe read with interest the study by Asselah et al. published in the Journal of Hepatology [1] on the impact of IL28B SNPs on the outcome of antiviral therapy in HCV genotype 4 patients showing a significant and independent association between the polymorphism in rs12979860 of the IL28B gene and the treatment response in a cohort of 82 consecutive treatment-naïve patients. In the discussion, the authors surprisingly state that to the best of their knowledge this was the first study to examine this association in this specific group of patients with HCV-4 infection. Full-Text PDF Open Access Indeed, genotype 4 (HCV-4) is the most frequent cause of chronic hepatitis C in the Middle-East, and sub-Saharan Africa. It has recently spread to Southern Europe, particularly among intravenous drug users and immigrants [[1]Antaki N. Craxi A. Kamal S. Moucari R. Van der Merwe S. Haffar S. et al.The neglected hepatitis C virus genotypes 4, 5 and 6: an international consensus report.Liver Int. 2010; 30: 342-355Crossref PubMed Scopus (156) Google Scholar]. HCV-4 is mainly found in Egypt, the country with the highest prevalence of HCV worldwide (15%), where HCV-4 represents 90% of all HCV cases. For genotype 4 infected patients, the most effective therapy to eradicate the virus remains a combination of pegylated interferon (PegIFN) alpha and ribavirin. In this specific genotype 4 population, there is a major medical need for studies on natural history, new treatments, and predictors of response. We performed a study in a well-characterized cohort of HCV-4 patients, to investigate the association of IL28B polymorphism with response to treatment or liver disease severity [[2]Asselah T. De Muynck S. Broët P. Masliah-Planchon J. Blanluet M. Bièche I. et al.IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C.J Hepatol. 2012; 56: 527-532Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar]. In our article, our well-characterized unique large cohort was defined based on its ethnic origin. In this cohort, three different ethnic groups were represented with 70 (43%) Egyptians, 53 (32%) Europeans, and 37 (23%) Sub-Saharan Africans. A liver biopsy was performed in 160 patients, of whom 78 (49%) had a mild fibrosis (F0–F1) and 82 (51%) a moderate to severe fibrosis (F2–F4). We did not observed an association between fibrosis stage and response to treatment; however, the proportion of patients with cirrhosis (F4) was relatively small (17.1%). Eighty-two patients received 48 weeks of PegIFNα and ribavirin. Among these, 43 patients (52%) obtained an SVR and 39 failed treatment (28 (32%) obtained a non-response and 11 (16%) were relapsers). Among our treated patients, the proportion of rs12979860 CC was 26.8%; CT was 52.4%, and TT was 20.8%. Since in genotype 4 patients the treatment will remain PegIFN and ribavirin for several years, IL28B polymorphism may remain an important associated factor with response. Another study performed in Italy gave similar results with an association between IL28B polymorphism and SVR [[3]De Nicola S. Aghemo A. Rumi M.G. Galmozzi E. Valenti L. Soffredini R. et al.Interleukin 28B polymorphism predicts pegylated interferon plus ribavirin treatment outcome in chronic hepatitis C genotype 4.Hepatology. 2012; 55: 336-342Crossref PubMed Scopus (70) Google Scholar]. Of 112 treated patients (98 males, 75 of Egyptian descent, 26 with cirrhosis) 103 were included in the final analysis; five discontinued treatment for non-virologic reasons and four did not consent to genetic testing. Twenty-four (23%) were genotype CC, 65 (63%) CT, and 14 (14%) TT. Overall, 50 (49%) achieved an SVR: 21 (88%) CC patients versus 29 (37%) CT/TT. Further studies will be needed to demonstrate whether genotype 4-infected patients with good predictors of response, including IL28B CC, may benefit from shorten therapy. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.