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IFI35, mir-99a and HCV genotype to predict sustained virological response to pegylated-interferon plus ribavirin in chronic hepatitis C.

Abstract
Although, the treatment of chronic hepatitis C (CHC) greatly improved with the use of direct antiviral agents, pegylated-interferon (PEG-IFN) plus ribavirin remains an option for many patients, worldwide. The intra-hepatic level of expression of interferon stimulated genes (ISGs) and the rs12979860 CC genotype located within IFNL3 have been associated with sustained virological response (SVR), in patients with CHC. The aim of the study was to identify micro-RNAs associated with SVR and to build an accurate signature to predict SVR. Pre-treatment liver biopsies from 111 patients, treated with PEG-IFN plus ribavirin, were studied. Fifty-seven patients had SVR, 36 non-response (NR) and 18 relapse (RR). The expression of 851 human miRNAs and 30 selected mRNAs, including ISGs, was assessed by RT-qPCR. In the first group of patients (screen), 20 miRNAs out of the 851 studied were deregulated between NRs and SVRs. From the 4 miRNAs validated (mir-23a, mir-181a*, mir-217 and mir-99a), in the second group of patients (validation), 3 (mir-23a, mir-181a* and mir-99a) were down-regulated in NRs as compared to SVRs. The ISGs, studied, were accumulated in SVRs and IFNL3 rs12979860 CT/TT carriers compared respectively to NRs and CC carriers. Combining, clinical data together with the expression of selected genes and micro-RNAs, we identified a signature (IFI35, mir-99a and HCV genotype) to predict SVR (AUC:0.876) with a positive predictive value of 86.54% with high sensibility (80%) and specificity (80.4%). This signature may help to characterize patients with low chance to respond to PEG-IFN/ribavirin and to elucidate mechanisms of NR.
AuthorsEmilie Estrabaud, Kevin Appourchaux, Ivan Bièche, Fabrice Carrat, Martine Lapalus, Olivier Lada, Michelle Martinot-Peignoux, Nathalie Boyer, Patrick Marcellin, Michel Vidaud, Tarik Asselah
JournalPloS one (PLoS One) Vol. 10 Issue 4 Pg. e0121395 ( 2015) ISSN: 1932-6203 [Electronic] United States
PMID25844942 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • IFI35 protein, human
  • Intracellular Signaling Peptides and Proteins
  • MIRN99 microRNA, human
  • MicroRNAs
  • Ribavirin
  • Interferons
Topics
  • Adult
  • Aged
  • Antiviral Agents (pharmacology, therapeutic use)
  • Drug Therapy, Combination
  • Female
  • Gene Expression Regulation
  • Genome, Viral
  • Genotype
  • Hepacivirus (genetics)
  • Hepatitis C, Chronic (drug therapy, genetics, virology)
  • Humans
  • Interferons (pharmacology, therapeutic use)
  • Intracellular Signaling Peptides and Proteins (genetics, metabolism)
  • Liver (drug effects, metabolism, virology)
  • Male
  • MicroRNAs (genetics, metabolism)
  • Middle Aged
  • Ribavirin (pharmacology, therapeutic use)
  • Young Adult

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