title: A randomized, controlled study of thymosin-alpha1 therapy in patients with anti-HBe, HBV-DNA-positive chronic hepatitis B.
abstract: No consistently effective therapy is yet available for the treatment of chronic HBsAg, anti-HBe, HBV-DNA-positive hepatitis. A multicenter trial has shown that the response rates are not significantly different when patients with anti-HBe-positive hepatitis are treated with six-month course of thymosin-alpha1 or of interferon-alpha. However, since among these patients, interferon's real efficacy is still debated, with sustained biochemical response achieved in only a few of the treated patients, we conducted this controlled study to investigate the safety and efficacy of thymosin-alpha1 as compared with no treatment. Forty-four chronic hepatitis B virus (HBV) carriers, who were anti-HBe- and HBV-DNA-positive, were randomized, with stratification for the presence of cirrhosis at baseline liver biopsy, to receive either thymosin-alpha1 at a dose of 900 microg/m2 twice a week for six months or no treatment. At entry, both groups of patients were comparable for 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) after completion of therapy: one dropped out, and one developed hepatocellular carcinoma at six months. Thymosin-alpha1 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 treatment period and six months of follow-up. During the first year, there were six flares of hepatitis in the control group and five among the treated patients (P = NS), yielding a per year average of 0.3 and 0.23 flares per patient, respectively. Among the treated patients, median IgM anti-HBc levels were low with respect to baseline values 4-10 months after treatment started. None became HBsAg negative. In conclusion, these results indicate that, in anti-HBe, HBV-DNA-positive chronic hepatitis B, thymosin-alpha1 therapy alone does not increase the response rate, but may contribute to reduce the immune-mediated liver cell necrosis as indirectly assessed by ALT and IgM anti-HBc levels.
authors.affiliation: Divisione di Medicina Generale e Servizio di Epatologia, Ospedale Niguarda, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Zavaglia
authors.forename: R
authors.initials: R
authors.lastname: Severini
authors.forename: C
authors.initials: C
authors.lastname: Tinelli
authors.forename: J S
authors.initials: JS
authors.lastname: Franzone
authors.forename: A
authors.initials: A
authors.lastname: Airoldi
authors.forename: S
authors.initials: S
authors.lastname: Tempini
authors.forename: G
authors.initials: G
authors.lastname: Bettale
authors.forename: G
authors.initials: G
authors.lastname: Ideo
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D013947:Thymosin; D000077596:Thymalfasin