ment for anti-HBe-positive chronic hepatitis. The benefit It has recently been shown that thymosin-a 1 (T-a 1 ), a of this agent in producing long-term inhibition of HBV synthetic polypeptide of thymic origin, is able to proreplication must be confirmed by future trials. (HEPAmote disease remission and inhibition of hepatitis B vi-TOLOGY 1996;24:774-777.) rus (HBV) replication in patients affected by hepatitis B e antigen (HBeAg)-positive chronic active hepatitis. We evaluated the efficacy and safety of T-a 1 treatment in Various subgroups of hepatitis B surface antigen (HBsAg)patients with hepatitis B e antibody (anti-HBe) and positive patients with chronic hepatitis have been identified. HBV-DNA-positive chronic hepatitis. Thirty-three pa-Typical patients have hepatitis B e antigen (HBeAg) and heptients were randomly assigned to receive either T-a 1 900 atitis B virus (HBV) DNA in serum during the active phase mg/m 2 body surface area twice weekly (17 patients) or of the disease and usually show disease remission if they 5 MU of interferon alfa (IFN-a) three times weekly (16 seroconvert to antibody to HBeAg (anti-HBe). A subset of patients) for 6 months. At baseline, both groups were patients, however, has been found to lack HBeAg but instead comparable concerning age, sex, liver histology, and alahas anti-HBe and HBV DNA in serum. 1 This form of hepatitis nine transaminase (ALT) levels. At the end of treatment, is more frequently seen in the Mediterranean region and in complete response (defined as ALT normalization and the Far East. The disease is characterized by a progressive HBV-DNA loss) occurred in 5 of 17 (29.4%) in the T-a 1 and relapsing course with fluctuations of viral replication 1,2 group and in 7 of 16 (43.8%) in the IFN-a group (P Å and a poor response to interferon alfa (IFN-a) therapy. 3-6 not significant). After a follow-up period of 6 months, a
In a placebo-controlled trial, thymosin-a 1 (T-a 1 ), a synthetic complete response was observed in 7 of 17 (41.2%) in the polypeptide of thymic origin, has been shown to promote dis-T-a 1 group and in 4 of 16 (25%) in the IFN-a group (P Å ease remission and cessation of HBV replication in patients n.s.). Compared with the results observed in a group of with HBeAg-positive chronic hepatitis B without significant 15 patients never treated with IFN-a and followed for 12 side effects. 7 Moreover, clinical trials using T-a 1 in the treatmonths, the rate of complete response was significantly ment of patients with immunodeficiency or cancer indicate higher in the IFN-a group at the end of therapy (1 of 15 that this agent is nontoxic, enhances immune responsiveness vs. 7 of 16, respectively; P õ .05) and in the T-a 1 group and augments specific lymphocyte functions, including at the end of follow-up (1 of 15 vs. 7 of 17, respectively; lymphoproliferative responses to mitogens, maturation of T P õ .05). Unlike IFN-a, T-a 1 was well tolerated by all cells, antibody production, and T-cell-mediated cytotoxicity. 8,9 patients. The only side effect, reported by some, was lo-On the basis of these observations, we started a multicencal discomfort at injection sites. The results of this trial ter randomized trial to compare the efficacy and the safety suggest that T-a 1 is able to reduce HBV replication in of T-a 1 versus IFN-a therapy in anti-HBe-and HBV-DNApatients affected by anti-HBe-positive chronic hepatitis.
positive chronic active hepatitis. Furthermore, compared with IFN-a, T-a 1 is better tolerated and seems to induce a gradual and more sustained
PATIENTS AND METHODS
ALT normalization and HBV-DNA loss. In conclusion, T-a 1 appears to be a safe and effective alternative treat-
Patients. A total of 33 patients were enrolled in the study on the basis of the following criteria for entry: age between 18 and 60 years; presence of HBsAg in serum for at least 12 months; positive serum Abbreviations: HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HBV, tests for anti-HBe and HBV DNA, documented on four occasions,