Effects of triple-drug therapy with nitazoxanide, high-dose ribavirin and peginterferon-α-2a in patients with chronic hepatitis C

Authors


  • Author contribution: P. P. B., principal investigator, patient recruitment, patient evaluation, data collection and manuscript preparation; K. R., data collection, patient evaluation and manuscript preparation; N. J. S., data collection, patient management and patient follow up; N. K., data collection and patient evaluation; R. S. B. Jr, manuscript preparation and protocol design.
  • Financial support: none
  • Conflict of interest: P. P. B. has received educational grants from Salix Pharmaceuticals and Romark Laboratories, and serves on the advisory boards for Roche, Vertex Pharmaceuticals and Gilead.

Correspondence: Dr P. Patrick Basu, North Shore University Hospital, 5 Station Square, Forest Hills, NY 11375, USA. Email: basu.patrick@gmail.com

Abstract

Aim

The historical standard of care for patients with chronic hepatitis C virus (HCV) was peginterferon (PEG IFN) and ribavirin combination therapy, yielding sustained virological response (SVR) rates of 38–52% in HCV genotype 1 patients. This study evaluated a novel three-drug regimen of nitazoxanide and high-dose ribavirin as lead-in therapy, followed by PEG IFN-α-2a in triple therapy.

Methods

A prospective, open-label pilot study was conducted in treatment-naive patients with HCV genotype 1. Patients received nitazoxanide 500 mg twice a day for 2 weeks, then nitazoxanide plus ribavirin 1400 mg/day for 2 weeks, then nitazoxanide plus ribavirin plus PEG IFN-α-2a 180 μg weekly for 12 weeks, followed by ribavirin plus PEG IFN-α-2a for 12 weeks (48 weeks if HCV RNA negative after week 24). Primary outcome was SVR. Other outcomes included very rapid virological response (VRVR), rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and safety and tolerability.

Results

Thirty-three patients with a mean age of 46 years, detectable HCV RNA (64% with <600 000 IU/mL), and METAVIR fibrosis scores (F1:F2:F3) of 15%:49%:36% were enrolled. Outcomes were as follows: SVR, 67% (22/33); VRVR, 39% (13/33); RVR, 48% (16/33); EVR, 70% (23/33); and ETR, 67% (22/33). Most patients required at least one growth factor. Two patients discontinued because of adverse events.

Conclusion

This three-drug regimen was effective in achieving SVR in patients with HCV genotype 1. No patients relapsed, and the toxicity profile was favorable. Further studies on the role of nitazoxanide in the treatment of chronic HCV are warranted.

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