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Arch Hellen Med, 27(4), July-August 2010, 594-598


Treatment optimization of HBeAg-negative chronic viral hepatitis B with thymosin-α1

Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece

Chronic hepatitis B virus (HBV) infection is a widely prevalent and clinically significant condition with profound implications for health care costs worldwide. Interferon-α and direct antiviral nucleos(t)ide analogs such as lamivudine, entecavir, adefovir, telbivudine, tenofovir and clevudine, are effective in the therapy of chronic HBV infection, but efficacy is still found wanting, particularly in HBeAg-negative/anti-HBe-positive cases and in patients with lower levels of alanine aminotransferase. Well documented evidence supports the pivotal role of immunomodulation in the control of hepatitis B virus infection. Thymosin-α1, a 28-amino acid peptide derived from the amino end of the highly acidic protein prothymosin-α, is an immunomodulatory agent known to increase natural killer (NK), CD4 and CD8 cell counts, shift the immune response towards Th1 cells, increase MHC class I expression on virus infected cells, and inhibit viral replication by direct antiviral action. A differential cellular response has been observed within a range of prothymosin-α concentrations, and optimal concentrations associated with maximal response have been observed. These attributes of the parent molecule prothymosin-α can be assumed to be shared by thymosin-α1. Treatment of patients with chronic HBV infection with thymosin-α1, either alone or in combination with interferon-α, has yielded promising results. It is postulated that these results can be significantly improved by optimizing the dose of thymosin-α1 for individual patients to induce a maximum immunomodulatory response. Drug optimization will be determined by testing the mixed lymphocyte response of each patient to different doses of thymosin-α1, before the initiation of treatment.

Key words: Anti-HBe, Chronic hepatitis B, Hepatitis B virus, Thymosin-α1.

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