Polymorphisms of Hepatitis C virus non-structural protein 5A and core protein and clinical outcome of pegylated-interferon/ribavirin combination therapy

Ahmed El-Shamy, Soo Ryang Kim, Yoshi Hiro Ide, Noriko Sasase, Susumu Imoto, Lin Deng, Ikuo Shoji, Hak Hotta

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Objective: Hepatitis C virus (HCV genome) polymorphisms are thought to influence the outcome of pegylated-interferon/ribavirin (PEG-IFN/RBV) therapy. This study aimed to examine non-structural protein 5A (NS5A) polymorphisms, e.g. IFN/RBV resistance-determining region (IRRDR) and IFN sensitivity-determining region (ISDR), and core protein polymorphism as predictive therapeutic markers. Methods: Pretreatment sequences of NS5A and core regions were analyzed in 68 HCV-1b-infected patients treated with PEG-IFN/RBV. Results: Of 24 patients infected withHCV having an IRRDR with 6 or more mutations (IRRDR≥6), 18 (75%) patients achieved sustained virological response (SVR), whereas only 11 (25%) of 44 patients infected with HCV having IRRDR≤5 did. IRRDR≥6 was significantly associated with SVR (p < 0.0001). On the other hand, ISDR≥2 was significantly associated with relapse (either before [breakthrough] or after end-of-treatment response [ETR[-]relapse]) (p < 0.05) and a point mutation of the core protein from Arg to Gln at position 70 (Gln 70) was significantly associated with null-response (p < 0.05). Multivariate analysis identified IRRDR≥6 as the only viral genetic factor that independently predicted SVR. Conclusion: NS5A (IRRDR and ISDR) and core protein polymorphisms are associated with the outcome of PEG-IFN/RBV therapy for chronic hepatitis C. In particular, IRRDR≥6 is a useful marker for prediction of SVR.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalIntervirology
Volume55
Issue number1
DOIs
StatePublished - Nov 2011
Externally publishedYes

Keywords

  • Core protein
  • Hepatitis C virus
  • Interferon sensitivity-determining region
  • Interferon/ribavirin resistance-determining region
  • Non-structural protein 5A
  • Prediction
  • Sustained virological response

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