Add-on therapy of pitavastatin and eicosapentaenoic acid improves outcome of peginterferon plus ribavirin treatment for chronic hepatitis C

Motoyuki Kohjima, Munechika Enjoji, Tsuyoshi Yoshimoto, Ryoko Yada, Tatsuya Fujino, Yoko Aoyagi, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Naohiko Harada, Masayoshi Yada, Masaki Kato, Kazuhiro Kotoh, Manabu Nakashima, Naoya Sakamoto, Yasuhito Tanaka, Makoto Nakamuta

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13 Citations (Scopus)

Abstract

Despite the use of pegylated-interferon (peg-IFN) plus ribavirin combination therapy, many patients infected with hepatitis C virus (HCV)-1b remain HCV-positive. To determine whether addition of pitavastatin and eicosapentaenoic acid (EPA) is beneficial, the "add-on" therapy option (add-on group) was compared retrospectively with unmodified peg-IFN/ribavirin therapy (standard group). Association of host- or virus-related factors with sustained virological response was assessed. In HCV replicon cells, the effects of pitavastatin and/or EPA on HCV replication and expression of innate-immunity- and lipid-metabolism-associated genes were investigated. In patients infected with HCV-1b, sustained virological response rates were significantly higher in the add-on than standard group. In both groups, sustained virological response rates were significantly higher in patients with genotype TT of IL-28B (rs8099917) than in those with non-TT genotype. Among the patients with non-TT genotype, sustained virological response rates were markedly higher in the add-on than standard group. By multivariate analysis, genome variation of IL28B but not add-on therapy remained as a predictive factor of sustained virological response. In replicon cells, pitavastatin and EPA suppressed HCV replication. Activation of innate immunity was obvious in pitavastatin-treated cells and EPA suppressed the expression of sterol regulatory element binding protein-1c and low-density lipoprotein receptor. Addition of pitavastatin and EPA to peg-IFN/ribavirin treatment improved sustained virological response in patients infected with HCV-1b. Genotype variation of IL-28B is a strong predictive factor in add-on therapy. J. Med. Virol. 85:250-260, 2013. © 2012 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)250-260
Number of pages11
JournalJournal of Medical Virology
Volume85
Issue number2
DOIs
Publication statusPublished - Feb 2013

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

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