1. Add-on therapy of pitavastatin and eicosapentaenoic acid improves outcome of peginterferon plus ribavirin treatment for chronic hepatitis C
- Author
-
Yasuhito Tanaka, Kazuhiro Kotoh, Makoto Nakamuta, Tsuyoshi Yoshimoto, Motoyuki Kohjima, Munechika Enjoji, Kunitaka Fukuizumi, Yoko Aoyagi, Manabu Nakashima, Naoya Sakamoto, Tatsuya Fujino, Masayoshi Yada, Masaki Kato, Naohiko Harada, Nobuyoshi Fukushima, and Ryoko Yada
- Subjects
Adult ,Male ,Combination therapy ,Hepatitis C virus ,Biology ,medicine.disease_cause ,Antiviral Agents ,chemistry.chemical_compound ,Pharmacotherapy ,Virology ,Ribavirin ,medicine ,Humans ,Pitavastatin ,Aged ,Retrospective Studies ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,Viral Load ,medicine.disease ,Eicosapentaenoic acid ,Treatment Outcome ,Infectious Diseases ,Eicosapentaenoic Acid ,chemistry ,Quinolines ,RNA, Viral ,Drug Therapy, Combination ,Female ,Interferons ,Viral load ,medicine.drug - 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.
- Published
- 2012