Thalidomide in the treatment of chronic hepatitis C unresponsive to alfa-interferon and ribavirin

Immunomodulation of thalidomide is represented by the antiinflammatory effect through inhibition of tumor necrosis factor (alpha) and costimulatory effect on human CD8+ T cells. We investigated the efficacy and safety of a 24-wk course of thalidomide at a dosage of 200 mg/day in eight patients with HCV chronic hepatitis nonresponders to interferon (alpha) plus ribavirin. We observed a significant mean decrease of serum aminotransferases and (gamma)-glutamyltransferases of 39% and 61%, respectively (p= 0.017 and 0.02). Tumor necrosis factor-(alpha)in vitro production in mononuclear cells decreased with thalidomide in all the subjects (p= 0.028). Perforin- and granzyme-specific mRNA expression increased under thalidomide without statistical significance. A positive correlation between biochemical and immunological parameters was observed with higher increase of granzyme and perforin values in patients showing reduction of aminotransferases. Finally upregulation of T-helper 1 cytokine expression as mean interferon (gamma)/IL-10 ratio was evidenced. Thalidomide was well tolerated. In conclusion, thalidomide was able to reduce liver enzymes in six out of eight patients with chronic hepatitis C and to reduce tumor necrosis factor (alpha) production, representing a promising new approach for the treatment of HCV infection. (copyright) 2006 by Am. Coll. of Gastroenterology Published by Blackwell Publishing.