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.
Milazzo
Laura
L
Institute of Infectious and Tropical Diseases, University of Milan, Milan, Italy.
Biasin
Mara
M
Gatti
Nadia
N
Piacentini
Luca
L
Niero
Fosca
F
Zanone Poma
Barbara
B
Galli
Massimo
M
Moroni
Mauro
M
Clerici
Mario
M
Riva
Agostino
A
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001706:Biopsy; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin; D013792:Thalidomide