Lamivudine plus interleukin-12 combination therapy in chronic hepatitis B: Antiviral and immunological activity

✍ Scribed by Eirini I. Rigopoulou; Deepak Suri; Shilpa Chokshi; Ivana Mullerova; Steven Rice; Richard S. Tedder; Roger Williams; Nikolai V. Naoumov

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 381 KB
• Volume: 42
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.20888

✦ Synopsis

Interleukin-12 (IL-12) is an immunomodulatory cytokine that promotes cellular immunity. Pre-clinical data suggest that IL-12 inhibits hepatitis B virus (HBV) replication by stimulating interferon-gamma (IFN-gamma) production. We investigated whether a combination treatment with lamivudine plus recombinant human interleukin-12 (rhIL-12) will result in a greater and prolonged suppression of HBV replication in comparison with lamivudine monotherapy. Fifteen patients with HBeAg-positive chronic hepatitis B were randomized to receive either lamivudine alone for 24 weeks (group 1); combination of lamivudine for 16 weeks and rhIL-12 (200 ng/kg twice weekly), starting 4 weeks after initiation of lamivudine, for 20 weeks (group 2), or the same schedule as for group 2, with lamivudine and a higher dose of rhIL-12 (500 ng/kg, group 3). Serum HBV DNA levels, T-cell proliferation, frequency of virus-specific T-cells, and IFN-gamma production were evaluated serially during and 24 weeks posttreatment. Lamivudine plus rhIL-12/500 showed greater antiviral activity than lamivudine monotherapy. However, after stopping lamivudine in groups 2 and 3, serum HBV DNA increased significantly despite continuing rhIL-12 administration. Lamivudine plus rhIL-12 treatment was associated with a greater increase in virus-specific T-cell reactivity, IFN-gamma production, and an inverse correlation between the frequency of IFN-gamma-producing CD4+ T-cells and viremia. The T-cell proliferative response to HBcAg did not differ between the three groups. In conclusion, the addition of IL-12 to lamivudine enhances T-cell reactivity to HBV and IFN-gamma production. However, IL-12 does not abolish HBV replication in HBeAg-positive patients and does not maintain inhibition of HBV replication after lamivudine withdrawal.