Pitavastatin enhances antiviral efficacy of standard pegylated interferon plus ribavirin in patients with chronic hepatitis C: A prospective randomized pilot study
Authors: Masahiko Shimada, Shuhei Yoshida, Ryota Masuzaki, Detlef Schuppan
Journal: Journal of Hepatology (2011)

We read the article by Harrison et al. [[1]Harrison S.A. Rossaro L. Hu K.Q. Patel K. Tillmann H. Dhaliwal S. et al.Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy.Hepatology. 2010; 52: 864-874Crossref PubMed Scopus (119) Google Scholar] with great interest. The authors performed a retrospective analysis of serum cholesterol and statin use of patients in the IDEAL study. They found a significantly higher sustained virological response (SVR) among patients who took a statin prior to antiviral therapy compared to patients not using statins. However, this was not a prospective trial and they did not show the combined effect of statins with PEG-IFN plus ribavirin. In vitro studies showed antiviral efficacy with statins [[2]Ikeda M. Abe K. Yamada M. Dansako H. Naka K. Kato N. 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Since insulin resistance is increased in chronic hepatitis C infection [6Moucari R. Asselah T. Cazals-Hatem D. Voitot H. Boyer N. Ripault M.P. et al.Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis.Gastroenterology. 2008; 134: 416-423Abstract Full Text Full Text PDF PubMed Scopus (468) Google Scholar, 7Asselah T. Rubbia-Brandt L. Marcellin P. Negro F. Steatosis in chronic hepatitis C: why does it really matter?.Gut. 2006; 55: 123-130Crossref PubMed Scopus (338) Google Scholar] and also insulin resistance impairs SVR rate to PEG-IFN plus ribavirin [[8]Romero-Gomez M. Del Mar Viloria M. Andrade R.J. Salmeron J. Diago M. 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We performed a prospective, randomized, and controlled pilot trial of standard PEG-IFN-2b plus ribavirin, with or without the addition of pitavastatin, to prove if pitavastatin therapy can enhance virus suppression and elimination. A total of 42 CHC patients diagnosed with genotype 1b and with a viral load >5.0 Log IU/ml, who were treated with PEG-IFN-2b at 1.0–1.5 μg/kg/week, plus ribavirin at 800–1400 mg/day or 48 weeks were randomly assigned to receiving pitavastatin (1–2 mg/day) or no additional therapy for 48 weeks. Patients with diabetes mellitus or fatty liver were excluded. No significant difference was observed in the cumulative dose of PEG-IFN and RBV between the standard and pitavastatin treatment groups. Viral load was monitored at 4, 8, 12, 24, and 48 weeks after treatment initiation using TaqMan real-time PCR (BML, Inc., Japan, range of quantitation: 1.2–7.8 Log IU/ml). The level of HCV-RNA, SVR rate, adverse events, serum AST, ALT, and creatine kinase (CK) were evaluated and compared using the Mann–Whitney U test. The cumulative rate of patients in whom HCV-RNA became undetectable by standard combination therapy or standard therapy with added pitavastatin was 5% and 29% at 4 weeks (p = 0.0408), 33% and 57% at 8 weeks (p = 0.1256), 48% and 81% at 12 weeks (p = 0.0259), 62% and 86% at 24 weeks (p = 0.0830), and 67% and 86% at 48 weeks (p = 0.1522), respectively (Fig. 1A). SVR at 72 weeks was 67% for patients with triple therapy compared to 48% for patients with standard therapy alone (Fig. 1B). However, this difference did not yet reach statistical significance due to the low number of patients (p = 0.2123). No significant differences between those two groups were found in the rate of adverse drug events. Furthermore, no significant differences were observed in serum AST, ALT, and CK levels (not shown). There was no case in which the medication had to be discontinued prematurely due to side effects. In conclusion, in patients with CHC genotype 1b, the use of pitavastatin with PEG-IFN plus ribavirin increased the rate of patients with undetectable HCV viral load. Furthermore, the use of pitavastatin with PEG-IFN plus ribavirin increased slightly the SVR (not statistically significant). Of note, the addition of pitavastatin caused no adverse effects, and treatment could be continued in all patients within this pilot trial. Therefore, the addition of pitavastatin to standard antiviral therapy appears to be a promising option to increase SVR in patients with CHC, which will justify larger prospective clinical trials. The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. Contributors: M.S. and S.Y. contributed equally to the management of the patient, researching for and writing of this manuscript. R.M. commented on drafts and did literature searches. D.S. advised on, wrote, and revised the manuscript. All authors read and approved the final manuscript. Some aspects of this study were presented at the poster session of the 61st Annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, 2010, where it was awarded with an AASLD Poster Prize.