Relevance of baseline viral genetic heterogeneity and host factors for treatment outcome prediction in hepatitis C virus 1b-infected patients

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• dc.contributor.author Saludes, Verónica
• dc.contributor.author Bascuñana, Elisabet
• dc.contributor.author Jordana-Lluch, Elena
• dc.contributor.author Casanovas, Sònia
• dc.contributor.author Ardèvol, Mercè
• dc.contributor.author Soler, Esther
• dc.contributor.author Planas, Ramón
• dc.contributor.author Ausina, Vicente
• dc.contributor.author Martró, Elisa
• dc.date.accessioned 2025-01-13T08:30:56Z
• dc.date.available 2025-01-13T08:30:56Z
• dc.date.issued 2013
• dc.description.abstract Background. Only about 50% of patients chronically infected with HCV genotype 1 (HCV-1) respond to treatment with pegylated interferon-alfa and ribavirin (dual therapy), and protease inhibitors have to be administered together with these drugs increasing costs and side-effects. We aimed to develop a predictive model of treatment response based on a combination of baseline clinical and viral parameters. Methodology. Seventy-four patients chronically infected with HCV-1b and treated with dual therapy were studied (53 retrospectively −training group−, and 21 prospectively −validation group−). Host and viral-related factors (viral load, and genetic variability in the E1–E2, core and Interferon Sensitivity Determining Region) were assessed. Multivariate discriminant analysis and decision tree analysis were used to develop predictive models on the training group, which were then validated in the validation group. Principal Findings. A multivariate discriminant predictive model was generated including the following variables in decreasing order of significance: the number of viral variants in the E1–E2 region, an amino acid substitution pattern in the viral core region, the IL28B polymorphism, serum GGT and ALT levels, and viral load. Using this model treatment outcome was accurately predicted in the training group (AUROC = 0.9444; 96.3% specificity, 94.7% PPV, 75% sensitivity, 81% NPV), and the accuracy remained high in the validation group (AUROC = 0.8148, 88.9% specificity, 90.0% PPV, 75.0% sensitivity, 72.7% NPV). A second model was obtained by a decision tree analysis and showed a similarly high accuracy in the training group but a worse reproducibility in the validation group (AUROC = 0.9072 vs. 0.7361, respectively). Conclusions and Significance. The baseline predictive models obtained including both host and viral variables had a high positive predictive value in our population of Spanish HCV-1b treatment naïve patients. Accurately identifying those patients that would respond to the dual therapy could help reducing implementation costs and additional side effects of new treatment regimens.en
• dc.format.mimetype application/pdf
• dc.identifier.citation Saludes V, Bascuñana E, Jordana-Lluch E, Casanovas S, Ardèvol M, Soler E, et al. Relevance of baseline viral genetic heterogeneity and host factors for treatment outcome prediction in hepatitis C virus 1b-infected patients. PLoS ONE. 2013 Aug 28;8(8):e72600. DOI: 10.1371/journal.pone.0072600
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0072600
• dc.identifier.issn 1932-6203
• dc.identifier.uri http://hdl.handle.net/10230/69053
• dc.language.iso eng
• dc.publisher Public Library of Science (PLoS)
• dc.relation.ispartof PLoS ONE. 2013 Aug 28;8(8):e72600
• dc.rights © 2013 Saludes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Polimorfisme genèticca
• dc.subject.other Medicaments antivíricsca
• dc.subject.other Previsióca
• dc.title Relevance of baseline viral genetic heterogeneity and host factors for treatment outcome prediction in hepatitis C virus 1b-infected patientsen
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion