Due to the emergence of resistant hepatitis B virus (HBV), researchers are continually seeking new drugs for the treatment of chronic hepatitis B, especially ones that work by novel mechanisms.

Nitazoxanide - an antimicrobial agent - in a new class known as thiazolides is approved in the United States for the treatment of gastroenteritis caused by Cryptosporidium parvum and Giardia lamblia, and is in the late stages of development for Clostridium difficile infection.

A preclinical study presented at the recent Digestive Disease Week 2006 conference in Los Angeles showed that nitazoxanide is also active against HBV in vitro, and potentially in patients as well.

In Vitro Results

The antiviral activity of nitazoxanide and its active circulating metabolite, tizoxanide, in 2.2.15 cell cultures are shown in the table; lamivudine (Epivir-HBV) data are shown for comparison.

EC50 = 50% effective concentration; EC90 = 50% effective concentratio; CC50 = 50% cytotoxic concentration

Further in vitro experiments showed that nitazoxanide suppressed HBV surface and "e" antigen (HBsAg and HBeAg), suggesting a mechanism of action that differs from those of other antiviral drugs.

Patient Results

The authors also administered the drug to a 48-year-old Egyptian man with HBeAg-positive chronic hepatitis B refractory to lamivudine. He received 500 mg twice-daily oral nitazoxanide with food for 24 weeks, with evaluations including physical examination, laboratory safety tests, and HBV DNA quantification performed every four weeks.

After 4 weeks of treatment, the patient experienced a 2 log reduction in HBV viral load (from 5,250,000 copies/mm3 at baseline to 51,000 copies/mm3).

He experienced a slight increase in ALT (from 53 IU/L at baseline to 60 IU/L).

At weeks 8, 12, 16, 20 and 24, the patient had seroconverted to HBeAg-negative and he had undetectable HBV DNA and normal ALT.

No significant adverse events were reported.

Conclusions
The researchers concluded that their results suggest that nitazoxanide is effective in treating chronic hepatitis B, with a mechanism of action that differs from those of traditional antiviral drugs. The treated patient is being followed to determine duration of response, and a double-blind placebo-controlled trial is underway.

6/16/06

Reference
J Rossignol, BE Korba, SM Kabil. Nitazoxanide in treating chronic hepatitis B: in vitro activity and a clinical case report. Abstract T1852. Digestive Disease Week 2006. May 20-25, 2006. Los Angeles, CA.