dc.creator | Rigopoulou, E. I. | en |
dc.creator | Suri, D. | en |
dc.creator | Chokshi, S. | en |
dc.creator | Mullerova, I. | en |
dc.creator | Rice, S. | en |
dc.creator | Tedder, R. S. | en |
dc.creator | Williams, R. | en |
dc.creator | Naoumov, N. V. | en |
dc.date.accessioned | 2015-11-23T10:46:27Z | |
dc.date.available | 2015-11-23T10:46:27Z | |
dc.date.issued | 2005 | |
dc.identifier | 10.1002/hep.20888 | |
dc.identifier.issn | 2709139 | |
dc.identifier.uri | http://hdl.handle.net/11615/32643 | |
dc.description.abstract | 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-γ) 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-γ 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-γ production, and an inverse correlation between the frequency of IFN-γ-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-γ production. However, IL-12 does not abolish HBV replication in HBeAg-positive patients and does not maintain inhibition of HBV replication after lamivudine withdrawal. Copyright © 2005 by the American Association for the Study of Liver Diseases. | en |
dc.source.uri | http://www.scopus.com/inward/record.url?eid=2-s2.0-30944449094&partnerID=40&md5=3d71aead022dd9dd188ca53d1c3058ba | |
dc.subject | gamma interferon | en |
dc.subject | hepatitis B core antigen | en |
dc.subject | hepatitis B(e) antigen | en |
dc.subject | lamivudine | en |
dc.subject | recombinant interleukin 12 | en |
dc.subject | virus DNA | en |
dc.subject | adult | en |
dc.subject | antiviral activity | en |
dc.subject | arthralgia | en |
dc.subject | article | en |
dc.subject | asthenia | en |
dc.subject | CD4+ T lymphocyte | en |
dc.subject | cellular immunity | en |
dc.subject | clinical article | en |
dc.subject | clinical trial | en |
dc.subject | controlled clinical trial | en |
dc.subject | controlled study | en |
dc.subject | coughing | en |
dc.subject | drug megadose | en |
dc.subject | fatigue | en |
dc.subject | female | en |
dc.subject | fever | en |
dc.subject | flu like syndrome | en |
dc.subject | headache | en |
dc.subject | hepatitis B | en |
dc.subject | Hepatitis B virus | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | injection site reaction | en |
dc.subject | insomnia | en |
dc.subject | interferon production | en |
dc.subject | lymphocyte proliferation | en |
dc.subject | male | en |
dc.subject | monotherapy | en |
dc.subject | myalgia | en |
dc.subject | priority journal | en |
dc.subject | randomized controlled trial | en |
dc.subject | T lymphocyte | en |
dc.subject | treatment outcome | en |
dc.subject | treatment withdrawal | en |
dc.subject | viremia | en |
dc.subject | virus inhibition | en |
dc.subject | virus replication | en |
dc.subject | Adjuvants, Immunologic | en |
dc.subject | CD4-Positive T-Lymphocytes | en |
dc.subject | DNA, Viral | en |
dc.subject | Drug Therapy, Combination | en |
dc.subject | Hepatitis B Core Antigens | en |
dc.subject | Hepatitis B, Chronic | en |
dc.subject | Humans | en |
dc.subject | Interferon Type II | en |
dc.subject | Interleukin-12 | en |
dc.subject | Pilot Projects | en |
dc.subject | Recombinant Proteins | en |
dc.subject | Reverse Transcriptase Inhibitors | en |
dc.subject | T-Lymphocytes | en |
dc.title | Lamivudine plus interleukin-12 combination therapy in chronic hepatitis B: Antiviral and immunological activity | en |
dc.type | journalArticle | en |