HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin

Isabella Abbate, Oreste Lo Iacono, Rosa Di Stefano, Giuseppina Cappiello, Enrico Girardi, Roberta Longo, Donatella Ferraro, Giorgio Antonucci, Vito Di Marco, Mariacarmela Solmone, Antonio Craxì, Giuseppe Ippolito, Maria R. Capobianchi

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aims HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN α2b or STD-IFN α2b plus RBV. Methods HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy (T1) and at follow-up (T18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees. Results No correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load decline at 4 weeks of treatment. In the majority of SR, profound changes of quasispecies composition occurred during 4 weeks of treatment, while in NR virtually no major changes of pre-therapy variants were observed. Relapse showed both patterns of quasispecies evolution. Virus quasispecies after follow-up was similar to that found at T1 in both Relapsers and NR patients. Conclusions Baseline parameters of HVR-1 heterogeneity seem to be involved in the early response to treatment, and early response is associated with profound variations in the HVR-1 quasispecies. Viral quasispecies surviving early therapeutic pressure are most likely able to give rise to either virus rebound or persistence at T18.

Original languageEnglish
Pages (from-to)831-836
Number of pages6
JournalJournal of Hepatology
Volume40
Issue number5
DOIs
Publication statusPublished - May 2004

Keywords

  • HCV
  • HVR-1
  • HVR-1, hypervariable region-1
  • Interferon
  • NR, non-responder
  • NS, non-synonymous
  • PEG-IFN, pegylated-interferon
  • Quasispecies
  • RBV, ribavirin
  • Rel, relapser
  • S, synonymous
  • SR, sustained responder
  • STD-IFN, standard-interferon

ASJC Scopus subject areas

  • Gastroenterology

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