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

Abstract

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.

• Authors: Laura Milazzo, Mara Biasin, Nadia Gatti, Luca Piacentini, Fosca Niero, Barbara Zanone Poma, Massimo Galli, Mauro Moroni, Mario Clerici, Agostino Riva
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 101 Issue 2 Pg. 399-402 (Feb 2006) ISSN: 0002-9270 [Print] United States
• PMID: 16454849 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• Immunosuppressive Agents
• Interferon-alpha
• RNA, Viral
• Ribavirin
• Thalidomide

Topics

• Adult
• Aged
• Antiviral Agents (adverse effects, therapeutic use)
• Biopsy
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (drug therapy, pathology)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Interferon-alpha (adverse effects, therapeutic use)
• Male
• Middle Aged
• Polymerase Chain Reaction
• RNA, Viral (analysis)
• Ribavirin (adverse effects, therapeutic use)
• Thalidomide (therapeutic use)
• Treatment Outcome