Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B: a randomized controlled study.

aimTo observe the efficiency and safety of thymosin-alpha1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis.

methodsSixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-alpha1, twice a week (T-alpha1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-alpha) each day for fifteen days, then three times weekly (IFN-alpha group) for six months. The results between two groups treated with and the group untreated with IFN-alpha which was followed up for 12 mo (historical control group consisting of 30 patients) were compared, and three groups were comparable between each other (P>0.05) at baseline (age, sex, clinical history, biochemical, and serological parameters).

resultsAt the end of treatment, complete response, which was defined as alanine aminotransferase (ALT) normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 (31.0%) patients in the T-alpha1 group and in 15 of 33 (45.5%) patients in the IFN-alpha group (chi2=1.36, P>0.05). After a follow-up period of six months, a complete response was observed in 14 of 29 (48.3%) patients in the T-alpha1 group and in 9 of 33 (27.3%) patients in the IFN-alpha group (chi2=2.93, P>0.05). Compared with the results observed in the historical control (HC) group untreated with IFN-alpha which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-alpha group at the end of therapy (1 of 30 vs 15 of 33, chi2=14.72, P<0.001) and in the T-alpha1 group at the end of follow-up (1 of 30 vs 14 of 29, chi2=15.71, P<0.001). In T-alpha1 and IFN-alpha treatment groups, the area under (the plasma concentration time) curve (AUC) of negative HBV DNA and HBeAg was 34%, 17%, 31% and 19% smaller than that in the HC group. By the end of the follow-up period, the proportions of ALT normalization and negative HBV DNA in the T-alpha1 group were significantly higher than those in the IFN-alpha and HC groups. The odds of ALT normalization and negative HBV DNA at the end of the follow-up was three-fold higher in the T-alpha1 group than in the IFN-alpha group. Unlike IFN-alpha, T-alpha1 was well tolerated by all patients, and no side effects appeared in T-alpha1 group.

conclusionThe results suggest that a 6-mo course of T-alpha1 therapy is effective and safe in patients with chronic hepatitis B. T-alpha1 is able to reduce HBV replication in patients with chronic hepatitis B. Furthermore, T-alpha1 is better tolerated than IFN-alpha and can gradually induce more sustained ALT normalization and HBV DNA and HBeAg loss. However, a response rate of 48.3% is still less ideal. A more effective therapeutic approach warrants further study.