A randomized, controlled study of thymosin-alpha(1) therapy in patients with anti-HBe, HBV-DNA-positive chronic hepatitis B

No consistently effective therapy is yet available for the treatment of chr onic HBsAg, anti-HBe. HBV-DNA-positive hepatitis. A multicenter trial has s hown that the response rates are not significantly different when patients with anti-HBe-positive hepatitis are treated with six-month course of thymo sin-alpha(1) or of interferon-alpha. However, since among these patients, i nterferon's real efficacy is still debated, with sustained biochemical resp onse achieved in only a few of the treated patients, we conducted this cont rolled study to investigate the safety and efficacy of thymosin-alpha(1) as compared with no treatment. Forty-four chronic hepatitis B virus (HBV) car riers, who were anti-HBe- and HBV-DNA-positive. were randomized, with strat ification for the presence of cirrhosis at baseline liver biopsy, to receiv e either thymosin-alpha(1) at a dose of 900 mu g/m(2) twice a week for six months or no treatment. At entry, both groups of patients were comparable f or sex, age, liver histology, ALT, IgM anti-HBc, and HBV-DNA levels. Forty- two patients were followed-up for 20 months (median; range 12-32 months) af ter completion of therapy: one dropped out, and one developed hepatocellula r carcinoma at six months. Thymosin-alpha(1), treatment had no side effects . Six months after the end of the therapy, HBV-DNA was negative and ALT had normalized in 14% of treated cases and in 4.5% of control group, while IgM anti-HBc was negative (<0.200) in 14% of the treated patients and in 4.5% of the controls. Among the treated patients, the: median ALT levels stayed significantly lower compared to the pretreatment values during the treatmen t period and six months of follow-up. During the first year, there were six hares of hepatitis in the control group and five among the treated patient s (P = NS), yielding a per year average of 0.3 and 0.23 flares per patient, respectively. Among the treated patients, median IgM anti-HBe levels were low with respect to baseline values 4-10 months after treatment started. No ne became HBsAg negative. In conclusion, these results indicate that, in an ti-HBe, HBV-DNA-positive chronic hepatitis B, thymosin-alpha(1) therapy alo ne does not increase the response rate, but may contribute to reduce the im mune-mediated liver cell necrosis as indirectly assessed by ALT and IgM ant i-HBc levels.