title: Add-on therapy of pitavastatin and eicosapentaenoic acid improves outcome of peginterferon plus ribavirin treatment for chronic hepatitis C.
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.
authors.affiliation: Department of Gastroenterology, Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujino
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Fukushima
authors.forename: Kunitaka
authors.initials: K
authors.lastname: Fukuizumi
authors.forename: Naohiko
authors.initials: N
authors.lastname: Harada
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yada
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakashima
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination / Q000379:methods; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage*; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D011804:Quinolines; D012367:RNA, Viral; D012254:Ribavirin; D007372:Interferons; D015118:Eicosapentaenoic Acid; C108475:pitavastatin