Reply to “Triple or dual therapy for HCV-1 naive patients? Optimizing selection tools”
Authors: Orazio Palmieri, Maria Rosa Valvano, Maurizio Margaglione, Angelo Andriulli
Journal: Journal of Hepatology (2014)

Triple or dual therapy for HCV-1 naive patients? Optimizing selection toolsJournal of HepatologyVol. 61Issue 1PreviewWe read with interest the paper by Andriulli et al. [1] about the identification of naïve HCV-1 patients who can be treated with dual therapy according to baseline and on-treatment parameters. Important predictive factors of sustained virological response (SVR) are the IL28B single-nucleotide polymorphisms (SNPs), however the authors considered only the rs12979860 SNP, forgetting the more important rs8099917 [2–4]; this is, in our opinion, not just an academic discussion, because the role of rs8099917 has been clarified and deepened in several studies and we think it should be included as best SVR predictor in the genotype 1 [2–4]. Full-Text PDF Open AccessIdentification of naïve HCV-1 patients with chronic hepatitis who may benefit from dual therapy with peg-interferon and ribavirinJournal of HepatologyVol. 60Issue 1PreviewThe pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. Full-Text PDF We thank Dr. Boglione and colleagues [[1]Boglione L, De Nicolò A, Di Perri G, D'Avolio A. Triple or dual therapy for HCV-1 naive patients? Optimizing selection tools. J Hepatol 2014;61:Google Scholar] for their comments on our recently published paper on the identification of naïve HCV-1 patients with chronic hepatitis who may benefit from dual therapy with peg-interferon (PegIFN) and ribavirin (RBV) [[2]Andriulli A. Di Marco V. Margaglione M. Ippolito A.M. Fattovich G. Smedile A. et al.Identification of naïve HCV-1 patients with chronic hepatitis who may benefit from dual therapy with peg-interferon and ribavirin.J Hepatol. 2014; 60: 16-21Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar]. To date, several single nucleotide polymorphisms (SNPs) in the genes encoding for IFN-λ1 (IL29), IFN-λ2 (IL28A), IFN-λ3 (IL28B), and IFN-λ4 (IFNL4) have been established as predictors of treatment response to PegIFN/RBV [3Afdhal N.H. McHutchison J.G. Zeuzem S. Mangia A. Pawlotsky J.M. Murray J.S. et al.Pharmacogenetics and hepatitis C meeting participants. Hepatitis C pharmacogenetics: state of the art in 2010.Hepatology. 2011; 53: 336-345Crossref PubMed Scopus (131) Google Scholar, 4Prokunina-Olsson L. Muchmore B. Tang W. Pfeiffer R.M. Park H. Dickensheets H. et al.A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus.Nat Genet. 2013; 45: 164-171Crossref PubMed Scopus (720) Google Scholar]. Among the identified SNPs, rs8099917, rs12979860, and the newly ss469415590 polymorphisms have been extensively investigated. Although with conflicting results, the question about which of the aforementioned SNPs, alone or in combination, is (or are) the best baseline marker(s) of SVR in patients HCV1 is still debated. Dr. Boglione et al. argue that the contemporary evaluation of the two SNPs of the IL28B locus may portend greater information on the actual outcome of therapy, as the rs12979860 could better predict RVR, whereas the rs8099917 would be more informative for SVR. We addressed this point in a subsequent manuscript where 539 patients of the entire cohort, for whom blood samples were available, were genotyped for the two SNPs [[5]Palmieri O. Ippolito A.M. Margaglione M. Valvano M.R. Gioffreda D. Fasano M. et al.Variation in genes encoding for interferon λ-3 and λ-4 in the prediction of HCV-1 treatment-induced viral clearance.Liver Int. 2013; https://doi.org/10.1111/liv.12411Crossref PubMed Scopus (10) Google Scholar]. In our patients the rs12979860 resulted to have a greater impact of the rs8099917 for either RVR (OR = 4.69, 95% CI 3.00–7.34 vs. OR = 3.01, 95% CI 1.97–4.59) and SVR (OR = 5.15, 95% CI 3.32–7.98 vs. OR = 2.46, 95% CI 1.72–3.51). Moreover, we entered the two SNPs together with the new ss469415590 dinucleotide variant (located in IFNL4 gene) into a multiple logistic model and the hit SNP appeared to be the rs12979860CC genotype, as it was the only one to retain an independent prediction power for SVR (OR = 3.39; 95% CI 1.61–7.13). The discrepancy between our data and the referenced results by Stättermayer et al. [[6]Stättermayer A.F. Stauber R. Hofer H. Rutter K. Beinhardt S. Scherzer T.M. et al.Impact of IL28B genotype on the early and sustained virologic response in treatment-naïve patients with chronic hepatitis C.Clin Gastroenterol Hepatol. 2011; 9: e2Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar] could be explained by differences in the HCV genotypes between patients enrolled into the two studies: while our data refer to only patients with HCV-1, the Stättermayer cohort of patients was a mix population of patients infected by all HCV genotypes. A further point raised by Dr. Boglione concerns the capability of predicting SVR in patients with the rs12979860 non-CC type by determining the TT genotype of the rs8099917. In the accompanying Table 1, we stratified our patients by both genotypes: of the 420 individuals with non-CC type, SVR rates were documented in 33% (44/134), 29% (72/250), and 19% (7/36) of subjects with the rs8099917 subtypes TT, TG or GG, respectively.Table 1Genotypes distribution of rs12979860 and rs8099917 SNPs in IL28B locus and Sustained Virological Response (SVR). Open table in a new tab While we may agree with our colleagues that monitoring of ribavirin levels during therapy could also impact positively on the outcome of therapy, we have not considered this point in our work. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.