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World J Gastroenterol. Apr 21, 2009; 15(15): 1805-1808
Published online Apr 21, 2009. doi: 10.3748/wjg.15.1805
Treatment of chronic viral hepatitis with nitazoxanide and second generation thiazolides
Emmet B Keeffe, Jean-François Rossignol
Emmet B Keeffe, The Romark Institute for Medical Research, Tampa, Florida and Sausalito, California, United States and the Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Stanford, California 94304-1509, United States
Jean-François Rossignol, The Romark Institute for Medical Research, Tampa, Florida, United States and the Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Stanford, California 94304-1509, United States
Author contributions: Keeffe EB and Rossignol JF solely contributed to this article.
Correspondence to: Emmet B Keeffe, MD, Romark Laboratories, L.C., 2320 Marinship Way, Suite 250, Sausalito, California, 94965, United States. emmet.keeffe@romark.com
Telephone: +1-415-3321060
Fax: +1-415-3321067
Received: December 24, 2008
Revised: February 23, 2009
Accepted: March 2, 2009
Published online: April 21, 2009
Abstract

Nitazoxanide, the first thiazolide, was originally developed for the treatment of Cryptosporidium parvum. More recently, antiviral activity of nitazoxanide against hepatitis B virus (HBV) and hepatitis C virus was recognized in in vitro systems. These basic studies led to phase II clinical trials that demonstrated the safety and efficacy of nitazoxanide in combination with peginterferon, with or without ribavirin, in the treatment of chronic hepatitis C genotype 4. The sustained virologic response rate was 79% and 80% in two studies, which was higher than the response rate of 50% with the standard of care with peginterferon plus ribavirin. In very preliminary studies of patients with chronic hepatitis B, nitazoxanide suppressed serum HBV DNA and led to loss of hepatitis B e antigen in the majority of patients and hepatitis B surface antigen in approximately a quarter of patients. Randomized controlled studies of naive and nonresponder patients with chronic hepatitis C genotype 1 are underway, new second generation and controlled release thiazolides are being developed, and future studies of patients with chronic hepatitis B are planned.

Keywords: Hepatitis C, Hepatitis C virus, Nitazoxanide