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.

Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to omega-3 fatty acids

“…Nonetheless, there is support for a trial of LC n -3 fatty acid supplementation to address irritability and labile anger in these patients (100) – which would be an alternative to otherwise effective SSRI depression prophylaxis (101–104). Recently, supplementation with EPA was associated with improved anti-viral outcome during IFN-α therapy (105). …”

Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease

“…Several lipid modulating agents, which were initially tested for their cardioprotective roles, may increase the efficacy of antiviral therapies, such as insulin sensitizing drugs and statins. Since insulin resistance and steatosis can modify antiviral treatment outcome, and since IR and steatosis enhance progression of the disease, it has been proposed to combine standard of care treatment and administration of insulin sensitizer such as metformin [74] or thiazolidinedione to manage insulin resistance and in turn induce a SVR [75,76]. Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a limiting step of cholesterol synthesis, and are widely used to modulate cholesterol levels in patients at risk of heart disease, or with familial hypercholesterolemia.…”

Add‐on effects of fluvastatin in simeprevir/pegylated‐interferon/ribavirin combination therapy for patients with genotype 1 hepatitis C virus infection: A randomized controlled study

“…Therefore, there might not have been room for improvement in the SVR rate. Kohjima et al . reported that, when eicosapentaenoic acid and a statin were added to Peg‐IFN/RBV therapy for patients with HCV infection, the SVR rate improved remarkably in IL28B non‐TT patients (SVR rates were 5.6% and 37.9% in the control group and add‐on group, respectively).…”

“…In vitro HCV replication analysis indicated that statins suppressed HCV replication . In addition, the results of several clinical trials have indicated that adding a statin to Peg‐IFN and RBV combination therapy improved treatment outcomes . In those reports, statin add‐on treatment improved the SVR rate by more than 25% in some groups, including patients with the IL28B non‐TT genotype.…”