Investigational treatments of chronic hepatitis B virus infection
- Anna SF Lok, MD
Anna SF Lok, MD
- Professor of Medicine
- University of Michigan Medical School
The main aim of treatment for chronic hepatitis B is to suppress HBV replication before there is irreversible liver damage. This topic review will discuss experimental treatments of chronic hepatitis B. A general approach to patients with hepatitis B (including other treatment options) is presented separately. (See "Overview of the management of hepatitis B and case examples".)
A number of antiviral agents for the treatment of chronic hepatitis B continue to be evaluated in clinical trials.
Emtricitabine — Emtricitabine (FTC) is a nucleoside analogue that is structurally similar to lamivudine and has potent antiviral activity against HBV and HIV [1,2]. The largest published study included 248 patients with chronic HBV (both HBeAg positive and negative) who had never received prior treatment with an nucleoside/tide analogue and were randomly assigned to emtricitabine or placebo for 48 weeks . Histologic improvement (defined as a 2-point reduction in the Knodell necroinflammatory score) was observed significantly more often in the active treatment group (62 versus 25 percent). Loss of detectable HBV DNA also occurred significantly more often with emtricitabine (54 versus 2 percent). However, HBV mutants with resistance to emtricitabine were observed in 13 percent of patients while HBeAg seroconversion was not significantly different than placebo.
Although studies comparing emtricitabine with lamivudine (or other oral agents) have not been performed, these data suggest that emtricitabine (200 mg daily) does not offer a clinically meaningful advantage since rates of HBV DNA loss, HBeAg seroconversion, histologic improvement and the development of resistant mutations are similar. In addition, mutants that are resistant to emtricitabine are also resistant to lamivudine and telbivudine and less sensitive to entecavir. Thus, the role of emtricitabine monotherapy in the treatment of chronic hepatitis B is limited. Emtricitabine alone is not used in clinical practice, but emtricitabine coformulated with tenofovir as a single pill is sometimes used off label in patients with lamivudine-resistant HBV.
Drugs no longer under development — Several drugs showed initial promise but are no longer under development for a variety of reasons. These include famciclovir, val-d-cytosine (LdC), valtorcitabine, LB80380, alamifovir, and pradefovir. Clevudine was approved in Korea but subsequently withdrawn due to postmarketing reports of myopathy.
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- ANTIVIRAL AGENTS
- Drugs no longer under development
- NOVEL ANTIVIRAL APPROACHES
- Viral entry inhibitors
- ccc DNA inhibitors
- Agents that decrease transcription and/or stability of HBV RNA
- Inhibitors of nucelocapsid assembly
- Inhibitors of HBsAg or HBV virion secretion
- Immunomodulatory agents
- - Thymosin
- - Cytokines
- - Blocking suppressive cytokines and regulatory T-cells
- HBV vaccines
- - S and pre-S vaccines +/- antiviral therapy
- - DNA vaccination
- - T cell vaccines
- - Other strategies
- Toll-like receptor (tlr) agonists
- Adoptive immunity transfer
- THERAPY AIMED AT IMPROVING FIBROSIS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS