A randomized, controlled, clinical study of thymosin alpha-1 versus interferon-alpha in [corrected] patients with chronic hepatitis B lacking HBeAg in China [corrected]

J Chin Med Assoc. 2005 Feb;68(2):65-72. doi: 10.1016/s1726-4901(09)70137-6.

Abstract

Background: This study was designed to compare the efficacy and safety of thymosin-alphal (T-alpha1) with that of interferon-alpha (IFN-alpha) in patients with chronic hepatitis B who were positive for hepatitis B virus (HBV) DNA and hepatitis B envelope antibody (anti-HBe).

Methods: Fifty-six patients were randomly divided into groups A and B. Both groups were comparable (p > 0.05) at baseline regarding age, sex, and alanine aminotransferase (ALT) levels. Group A patients received T-alpha1 1.6 mg subcutaneously twice weekly, while group B patients received IFN-alpha 5 million IU daily for 15 days, then thrice weekly for 6 months. Results from the 2 groups were compared with data from a group of 30 patients never treated with IFN-alpha and who were followed-up for 12 months (historical control [HC] group); the 3 groups were comparable (p > 0.05).

Results: After treatment, a complete response (ALT normalization and HBV DNA loss) occurred in 8 of 26 patients in group A (30.8%) and 14 of 30 in group B (46.7%; chi2 = 1.476, p = 0.224). After a follow-up period of 6 months, a complete response was observed in 11 of 26 patients in group A (42.3%) and 7 of 30 in group B (23.3%; chi2 = 2.299, p = 0.129). The rate of complete response was significantly greater in the IFN-alpha than HC group at the end of therapy (46.7% vs 3.3%; chi2 = 15.022, p = 0.0001), and in the T-alphal than HC group at the end of follow-up (42.3% vs 3.3%; chi2 = 12.566, p = 0.0001). Ten of the 12 T-alphal responders (i.e. partial responders; 83.3%) experienced sustained, non-detectable HBV DNA after 6 months' treatment; 6 of the 14 T-alphal non-responders (42.9%) showed a delayed response of non-detectable HBV DNA during the follow-up period. Corresponding values for group B patients were 50% (9/18) and 0% (0/12). The rate of delayed response was significantly higher in group A than the other 2 groups (chi2 = 6.686, p = 0.010; chi2 = 4.964, p = 0.038), whereas the rate of flare was higher in group B than in the other 2 groups (chi2 = 3.445, p = 0.063; chi2 = 7.668, p = 0.006), during the follow-up period. Unlike IFN-alpha, T-alphal was well tolerated, i.e. no adverse effects were noted in group A.

Conclusion: These results suggest that a 6-month course of T-alpha1 therapy is effective and safe in patients with anti-HBe-positive chronic hepatitis B; T-alpha1 can reduce HBV replication in such patients. Compared with IFN-alpha, T-alpha1 is better tolerated and seems to induce a gradual and more sustained normalization of ALT and loss of HBV DNA. Combination therapy with T-alpha1 and IFN-alpha or nucleoside analogs for hepatitis B warrants further study.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Adult
  • Alanine Transaminase / drug effects
  • Alanine Transaminase / metabolism
  • Antiviral Agents / therapeutic use
  • DNA, Viral / metabolism
  • Female
  • Hepatitis B Antigens / immunology
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Thymalfasin
  • Thymosin / analogs & derivatives*
  • Thymosin / therapeutic use*
  • Treatment Outcome

Substances

  • Adjuvants, Immunologic
  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Antigens
  • Hepatitis B Surface Antigens
  • Interferon-alpha
  • Thymosin
  • Alanine Transaminase
  • Thymalfasin