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 24 May 2018

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News

Lamivudine plus interleukin-12 enhances immunity in Hep B

The most recent issue of Hepatology shows that the addition of interleukin-12 to lamivudine enhances T-cell reactivity to Hepatitis B virus, and interferon-gamma production.

News image

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Interleukin-12 is an immunomodulatory cytokine that promotes cellular immunity.

Pre-clinical data suggest that interleukin-12 inhibits Hepatitis B virus replication by stimulating interferon-gamma production.

Dr Nikolai Naoumov and colleagues from England investigated if a combination treatment will prolong suppression of Hep B replication.

The researchers assessed lamivudine plus recombinant human interleukin-12 in comparison with lamivudine monotherapy.

The research team included 15 patients with Hepatitis B e-antigent-positive and chronic Hepatitis B.

The patients were randomized to receive either lamivudine alone for 24 weeks in Group 1.

Interleukin-12 monotherapy does not abolish Hepatitis B replication
Hepatology

Group 2 included patients randomized to a combination of lamivudine for 16 weeks and recombinant human interleukin-12 ng/kg twice weekly.

The combination treatment started 4 weeks after initiation of lamivudine, and continued for 20 weeks.

In Group 3, the same schedule was followed as for group 2, only with lamivudine and a higher dose of recombinant human interleukin-12 of 500 ng/kg.

Serum Hepatitis B virus DNA levels, T-cell proliferation, frequency of virus-specific T-cells, and interferon-gamma production were evaluated.

The researchers evaluated these markers serially during and 24 weeks posttreatment.

The team found that lamivudine plus recombinant human interleukin-12 showed greater antiviral activity than lamivudine monotherapy.

However, after stopping lamivudine in Groups 2 and 3, serum Hepatitis B virus DNA increased significantly despite continued use of recombinant human interleukin-12.

Lamivudine plus recombinant human interleukin-12 treatment was associated with a greater increase in virus-specific T-cell reactivity, and interferon-gamma production.

The researchers noted an inverse correlation between the frequency of interferon-gamma producing CD4+ T-cells and viremia.

The research team observed that the T-cell proliferative response to Hepatitis B c-antigen did not differ between the 3 groups.

Dr Naoumov's team concludes, “The addition of interleukin-12 to lamivudine enhances T-cell reactivity to Hepatitis B virus and interferon-gamma production.”

“However, interleukin-12 does not abolish Hepatitis B replication in Hepatitis B e-antigen-positive patients.”

“It also does not maintain inhibition of Hepatitis B virus replication after lamivudine withdrawal.”

Hepatol 2005: 42(5): 1028-36
02 November 2005

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