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Combination therapy for chronic hepatitis B virus infection

Anna SF Lok, MD
Section Editor
Rafael Esteban, MD
Deputy Editor
Jennifer Mitty, MD, MPH


Monotherapy with a single antiviral agent or interferon is unlikely to be sufficient for the eradication of hepatitis B virus (HBV) infection in the majority of patients who are chronically infected. With the availability of several medications, it is now possible to contemplate combination therapy for hepatitis B [1]. Such an approach has proven to be beneficial in patients with HIV infection and those with chronic hepatitis C. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient" and "Overview of the management of chronic hepatitis C virus infection".)

Ideally, therapeutic agents used in combination therapy should have additive or synergistic activity against HBV, delay or prevent the development of drug resistance, have no added toxicity, and promote restoration of immune response to HBV. The question is which agents to combine: two nucleos(t)ide analogs or one nucleos(t)ide analog plus interferon?

This topic review will summarize experience with combination therapy for chronic hepatitis B virus infection. Early experience involves the addition of another agent to lamivudine (see "Lamivudine monotherapy for chronic hepatitis B virus infection"). None of the combination approaches has been approved for routine use.


The combination of lamivudine and interferon seems logical because monotherapy with each agent is effective, and lamivudine and interferon have different mechanisms of action. However, disparate results have been described in controlled trials.

Treatment-naïve patients — There are conflicting data on the outcome after combination therapy in treatment-naïve patients [2-4]. One trial included 230 patients from Europe, Canada, and Australia who were randomly assigned to one of three treatment arms [2]:

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Literature review current through: Nov 2017. | This topic last updated: Nov 28, 2016.
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