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Combination therapy with a nucleos(t)ide analogue and interferon for chronic hepatitis B: simultaneous or sequential

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Abstract

Currently available antiviral treatment for chronic hepatitis B virus infection can be divided into two classes of therapeutic agents: nucleos(t)ide analogues (NAs) and interferon (IFN). The major advantages of NAs are good tolerance and potent antiviral activity associated with high rates of on-treatment response to therapy; the advantages of IFN include a finite course of treatment, absence of drug resistance, and an opportunity to obtain a post-treatment durable response to therapy. The use of these two antiviral agents with different mechanisms of action in combination is theoretically an attractive approach for treatment. Here, we have reviewed previous reports of either simultaneous or sequential combination therapy with NA and IFN for chronic hepatitis B patients. In previous studies comparing the lamivudine/IFN combination and lamivudine monotherapy in a finite course, combination therapy was associated with higher rates of sustained post-treatment response and lower rates of drug resistance than lamivudine monotherapy. However, NAs such as lamivudine are generally administered indefinitely because of high rates of post-treatment relapse. In addition, concern for drug resistance has decreased significantly with newer, high-potency NAs even when administered alone. In previous studies comparing the lamivudine/IFN combination and IFN monotherapy, the combination therapy showed greater on-treatment viral suppression, but no difference was observed in the post-treatment sustained response. Thus, whether combination therapy confers an additional benefit compared to monotherapy for treating chronic hepatitis B remains unclear. The efficacy of IFN in combination with a more potent NA, such as entecavir or tenofovir, remains to be comprehensively evaluated.

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Abbreviations

ALT:

Alanine aminotransferase

CccDNA:

Covalently closed circular DNA

HBcrAg:

Hepatitis B core-related antigen

HBeAg:

Hepatitis B e antigen

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

IFN:

Interferon

NA:

Nucleos(t)ide analogue

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Conflict of interest

Dr. S. Nishiguchi has received research grants from Bristol-Myers K.K., MSD K.K., and Chugai Pharmaceutical Co., Ltd. Dr. N. Kawada has received grants from Bristol-Myers K.K., MSD K.K., and Chugai Pharmaceutical Co., Ltd.

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Authors and Affiliations

  1. Department of Hepatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan

    Masaru Enomoto, Akihiro Tamori & Norifumi Kawada

  2. Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

    Shuhei Nishiguchi

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  1. Masaru Enomoto
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  2. Akihiro Tamori
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  3. Shuhei Nishiguchi
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  4. Norifumi Kawada
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Correspondence to Masaru Enomoto.

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Enomoto, M., Tamori, A., Nishiguchi, S. et al. Combination therapy with a nucleos(t)ide analogue and interferon for chronic hepatitis B: simultaneous or sequential. J Gastroenterol 48, 999–1005 (2013). https://doi.org/10.1007/s00535-012-0742-5

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