Hepatitis B Medication

Updated: Sep 22, 2017
  • Author: Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP, AGAF; Chief Editor: BS Anand, MD  more...
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Medication Summary

The goals of pharmacotherapy in patients with hepatitis B disease are to reduce the risk of progression of disease, prevent transmission to others, and decrease complications.

Currently, pegylated interferon alfa (PEG-IFN-a), entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are the first-line agents in the treatment of hepatitis B disease. These are the main treatment drugs approved globally for this disease, although ongoing development and clinical trials are investigating new types of medications, such as encapsidation inhibitors, entry inhibitors, TLR7 agonists, and therapeutic vaccines.



Class Summary

Interferons are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions.

Peginterferon alfa 2a (Pegasys)

Peginterferon alfa-2a binds to cell surface receptors in a cascade of protein interactions, resulting in gene transcription. These stimulated genes inhibit viral replication in infected cells, cell proliferation, and immunomodulation. Peginterferon alfa-2a is indicated for adults with hepatitis B e antigen (HBeAg)–positive and HBeAg-negative chronic hepatitis B disease with compensated liver disease and evidence of viral replication and liver inflammation.

Peginterferon alfa-2a is also FDA approved for the treatment of chronic hepatitis C, alone or in combination with ribavirin, in patients not previously treated with interferon alfa, and with compensated liver disease.

Interferon alfa-2b (Intron A)

Interferon alfa-2b (Intron A)

Interferon alfa-2b is a protein product manufactured by recombinant DNA technology. Its mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.

The immunomodulatory effects of interferon alfa-2b include enhancement of cytolytic T-cell activity, stimulation of natural killer cell activity, amplification of human leukocyte antigen (HLA) class I protein on infected cells, and suppression of tumor cell proliferation. The direct antiviral activity of interferon alfa-2b activates viral ribonucleases and inhibits viral entry into cells and viral replication. A direct antifibrotic effect has been postulated.

Before initiation of therapy with interferon alfa-2b, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cells, and bone marrow hairy cells. Monitor the patient periodically (eg, monthly) during treatment to determine his/her response to therapy. If the patient's condition does not respond within 4 months, discontinue treatment.

If a response occurs, continue treatment until no further improvement is observed. Whether continued treatment is beneficial after that time remains unknown.


Antihepadnaviral, Reverse Transcriptase inhibitors

Class Summary

Antiviral agents interfere with viral replication and weaken or abolish viral activity.

Tenofovir disoproxil fumarate (Viread)

Tenofovir is a nucleotide analogue (adenosine monophosphate) reverse transcriptase and hepatitis B virus (HBV) polymerase inhibitor.

Tenofovir may be used as first-line therapy for treatment-naïve patients. It is preferred as additional therapy in patients with lamivudine, telbivudine, or entecavir resistance. This agent has more potent antiviral activity than adefovir and can be used as a substitute in patients who do not have an adequate response to adefovir.

Entecavir (Baraclude)

Entecavir is a guanosine nucleoside analogue with activity against hepatitis B virus (HBV) polymerase. This agent competes with the natural substrate deoxyguanosine triphosphate (dGTP) to inhibit HBV polymerase activity (ie, reverse transcriptase). Entecavir is less effective for lamivudine-refractory HBV infection. This drug is indicated for treatment of chronic HBV infection and is available as a tablet and as an oral solution (0.05 mg/mL; 0.5 mg = 10 mL).

Lamivudine (Epivir, Epivir-HBV)

Lamivudine is a thymidine analogue that blocks viral replication by competitive inhibition of viral reverse transcriptase. There is evidence that an indirect immunomodulatory effect can be observed.

Relative to other oral treatments, lamivudine is lower in cost. Other agents, however, except for adefovir, are superior to lamivudine in suppression of viral replication. Another disadvantage to this therapy includes its high rate of drug resistance. The role of lamivudine in hepatitis B treatment is diminishing as alternate therapies become available.

Adefovir dipivoxil (Hepsera)

Adefovir is used to treat chronic hepatitis B disease. This agent is a prodrug that is converted to the diphosphate salt. The active drug is classified as an antiviral nucleotide reverse transcriptase inhibitor. It inhibits hepatitis B virus (HBV) DNA polymerase (reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate (dATP) and by causing DNA chain termination after its incorporation into viral DNA.

Telbivudine (Tyzeka)

Telbivudine is a nucleoside analogue approved by the US Food and Drug Administration (FDA) for chronic hepatitis B treatment. This drug inhibits hepatitis B viral DNA polymerase and is indicated for patients with evidence of ongoing hepatitis B viral replication and either persistent elevated aminotransferase activity or histologic evidence of active liver disease. Consider telbivudine for patients whose condition does not or is unlikely to respond to interferon or for patients who cannot tolerate interferon. Emergence of resistance is a major drawback of nucleoside analogue monotherapy.

Tenofovir AF (Vemlidy)

Tenofovir alafenamide (TAF) is a nucleotide reverse transcriptase inhibitor (NRTI) and a phosphonamidate prodrug of tenofovir. TAF, as a lipophilic cell-permeant compound, enters primary hepatocytes by passive diffusion and by the hepatic uptake transporters OATP1B1 and OATP1B3 and is converted to tenofovir diphosphate. Tenofovir diphosphate inhibits HBV replication through incorporation into viral DNA by the HBV reverse transcriptase, which results in DNA chain-termination.

Compared with tenofovir disoproxil fumarate (TDF), TAF is a more targeted form of tenofovir that has demonstrated high antiviral efficacy at a dose that is 10 times lower than TDF, as well as an improved renal and bone safety profile.

It is indicated for treatment of chronic hepatitis B virus infection in adults with compensated liver disease.