TY - JOUR
T1 - Thalidomide in the treatment of chronic hepatitis C unresponsive to alfa-interferon and ribavirin
AU - Milazzo, Laura
AU - Biasin, Mara
AU - Gatti, Nadia
AU - Piacentini, Luca
AU - Niero, Fosca
AU - Poma, Barbara Zanone
AU - Galli, Massimo
AU - Moroni, Mauro
AU - Clerici, Mario
AU - Riva, Agostino
PY - 2006/2
Y1 - 2006/2
N2 - Immunomodulation of thalidomide is represented by the antiinflammatory effect through inhibition of tumor necrosis factor α 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 α plus ribavirin. We observed a significant mean decrease of serum aminotransferases and γ-glutamyltransferases of 39% and 61%, respectively (p= 0.017 and 0.02). Tumor necrosis factor-αin 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 γ/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 α production, representing a promising new approach for the treatment of HCV infection.
AB - Immunomodulation of thalidomide is represented by the antiinflammatory effect through inhibition of tumor necrosis factor α 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 α plus ribavirin. We observed a significant mean decrease of serum aminotransferases and γ-glutamyltransferases of 39% and 61%, respectively (p= 0.017 and 0.02). Tumor necrosis factor-αin 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 γ/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 α production, representing a promising new approach for the treatment of HCV infection.
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U2 - 10.1111/j.1572-0241.2006.00350.x
DO - 10.1111/j.1572-0241.2006.00350.x
M3 - Article
C2 - 16454849
AN - SCOPUS:33644932179
VL - 101
SP - 399
EP - 402
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
SN - 0002-9270
IS - 2
ER -