A randomized controlled trial of thymosin-alpha1 versus interferon alfa treatment in patients with hepatitis B e antigen antibody--and hepatitis B virus DNA--positive chronic hepatitis B.
It has recently been shown that thymosin-alpha1(T-alpha1), a synthetic polypeptide of thymic origin, is able to promote disease remission and inhibition of hepatitis B virus (HBV) replication in patients affected by hepatitis B e antigen (HBeAg)-positive chronic active hepatitis. We evaluated the efficacy and safety of T-alpha1 treatment in patients with hepatitis B e antibody (anti-HBe) and HBV-DNA-positive chronic hepatitis. Thirty-three patients were randomly assigned to receive either T-alpha1 900 microg/m2 body surface area twice weekly (17 patients) or 5 MU of interferon alfa (IFN-alpha) three times weekly (16 patients) for 6 months. At baseline, both groups were comparable concerning age, sex, liver histology, and alanine transaminase (ALT) levels. At the end of treatment, complete response (defined as ALT normalization and HBV-DNA loss) occurred in 5 of 17 (29.4%) in the T-alpha1 group and in 7 of 16 (43.8%) in the IFN-alpha group (P = not significant). After a follow-up period of 6 months, a complete response was observed in 7 of 17 (41.2%) in the T-alpha1 group and in 4 of 16 (25%) in the IFN-alpha group (P = n.s.). Compared with the results observed in a group of 15 patients never treated with IFN-alpha and followed for 12 months, the rate of complete response was significantly higher in the IFN-alpha group at the end of therapy (1 of 15 vs. 7 of 16, respectively; P < .05) and in the T-alpha1 group at the end of follow-up (1 of 15 vs. 7 of 17, respectively; P < .05). Unlike IFN-alpha, T-alpha1 was well tolerated by all patients. The only side effect, reported by some, was local discomfort at injection sites. The results of this trial suggest that T-alpha1 is able to reduce HBV replication in patients affected by anti-HBe-positive chronic hepatitis. Furthermore, compared with IFN-alpha, T-alpha1 is better tolerated and seems to induce a gradual and more sustained ALT normalization and HBV-DNA loss. In conclusion, T-alpha1 appears to be a safe and effective alternative treatment for anti-HBe-positive chronic hepatitis. The benefit of this agent in producing long-term inhibition of HBV replication must be confirmed by future trials.
Andreone
P
P
Patologia Medica 1, Università di Bologna, Italy.
Cursaro
C
C
Gramenzi
A
A
Zavagliz
C
C
Rezakovic
I
I
Altomare
E
E
Severini
R
R
Franzone
J S
JS
Albano
O
O
Ideo
G
G
Bernardi
M
M
Gasbarrini
G
G
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood / Q000187:drug effects*; D005260:Female; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006513:Hepatitis B e Antigens / Q000097:blood / Q000187:drug effects*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D013947:Thymosin; D000410:Alanine Transaminase; D000077596:Thymalfasin