Pediatric Hepatitis B Medication

Interferon alfa has been the mainstay of treatment for chronic hepatitis B since its introduction in the mid 1980s; however, only 30-40% of patients respond to this therapy. Lamivudine and the newer nucleoside analogues (ie, famciclovir, lobucavir, and adefovir dipivoxil) directly block the replication of hepatitis B virus (HBV); they are highly effective, bioavailable, and extremely well tolerated. To date, interferon alfa-2b, peginterferon alfa-2a, lamivudine, adefovir, entecavir, and telbivudine are approved for hepatitis B by the US Food and Drug Administration (FDA).

Class Summary

Interferon may prevent the progression of acute hepatitis to the chronic stage and may promote more rapid resolution of viremia and normalization of serum aminotransferase levels. Several nucleoside analogues are active against HBV. The most widely used and studied is lamivudine, which has produced promising responses. However, relapse rates tend to be high after treatment is discontinued.

Interferon alfa-2b (Intron A)

Biologic interferons are proteins produced by host cells in response to viral infection. Three interferons have been identified, and each has antiviral and immunoregulatory actions: interferon-alfa is produced by B lymphocytes and monocytes; interferon-beta is produced by fibroblasts; and interferon-gamma is produced by T-helper and natural killer (NK) cells. Immunomodulatory effects of interferons are mediated by an increase in HLA class I antigen and FC receptor expression, an increased CD4/CD8 ratio, and activation of NK cell pathways.

Ideally, candidates for interferon therapy have evidence of ongoing viral replication (presence of hepatitis e antigen [HBeAg] or HBV DNA) for at least 6 months and either persistently increased serum aminotransferase activity or evidence of chronic hepatitis B infection on liver biopsy findings. Before recombinant interferon therapy, screening patients for at least 4-6 months to identify those who may be entering a period of spontaneous seroconversion to HBeAb is often beneficial.

Clinical variables associated with a favorable response to therapy are high pretherapy aminotransferase levels, low HBV DNA levels, and active disease at liver biopsy. Other, less useful, variables include female sex, acquisition of infection in adulthood, heterosexuality, HIV antibody negativity, and history of acute hepatitis.

Responses to interferon alfa-2b, is defined as a sustained loss of HBeAg and HBV DNA, with a normalization or near normalization of alanine aminotransferase (ALT) levels for at least 6 mo after therapy; this is observed in 25-40% of patients. Chinese children respond poorly to interferon therapy. Safety and effectiveness in patients aged 1-17 years have been established.

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 modulate inhibit viral replication in infected cells, cell proliferation, and immunomodulation. This agent is indicated for adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease and evidence of viral replication and liver inflammation.

Lamivudine (Epivir-HBV)

Lamivudine inhibits HBV DNA polymerase. Its use should be considered in patients with ongoing HBV replication, elevated aminotransferase activity, and histologic evidence of liver injury. Lamivudine is now considered first-line therapy, eclipsing interferon. Consider lamivudine in patients who fail or are unlikely to respond to interferon therapy or patients who cannot tolerate interferon.

Discontinue lamivudine only when repeated assays demonstrate HBeAg loss or seroconversion to HBeAb; the time for stopping treatment, however, is controversial. Results of a histologic study reported that lamivudine treatment for 3 years reduced necroinflammatory activity and reversed fibrosis (including cirrhosis) in most patients.

Emergence of resistance is the major drawback of nucleoside analogue monotherapy (incidence of resistance rises from 15-32% in the first year to 67-69% by the fifth year of treatment). The proper management of viral breakthrough in patients treated with lamivudine is not yet defined. Continuation of lamivudine appears to be warranted in most cases because the resistant strains of HBV seem to be attenuated and are associated with only mild liver injury.

Combination therapy with 2-3 nucleoside analogues may delay or prevent emergence of viral resistance, but clinical trials are needed.

Lamivudine is safe and effective in children aged 2-17 y. Note that the available dosage forms differ between Epivir and Epivir-HBV (formula specific for hepatitis B virus). Epivir-HVB is available as a 100-mg tablet or oral solution (5 mg/mL), whereas Epivir contains 150 mg/tablet or 10 mg/mL in an oral solution.

Adefovir dipivoxil (Hepsera)

Adefovir is indicated for chronic hepatitis B. This agent is an acyclic analogue of deoxyadenoside monophosphate and inhibits amplification of circular DNA in HBV-infected hepatocytes. When given daily for 48 weeks, it has been associated with significant improvement of histologic results, higher rate of HbeAg seroconversion, reduction of HBV DNA by 3 logs, and higher normalization rate of ALT when compared with placebo. The chance of adefovir-resistance development is low; however, a new adefovir-resistant mutant has been detected in 1.6% of patients at 96 weeks follow-up.

Entecavir (Baraclude)

A guanosine nucleoside analogue with activity against HBV polymerase, entecavir competes with natural substrate deoxyguanosine triphosphate to inhibit HBV polymerase activity (ie, reverse transcriptase). It is less effective for lamivudine-refractory HBV infection. This agent is indicated for treatment of chronic hepatitis B infection. It as available in tablets and oral solution (0.05 mg/mL; 0.5 mg = 10 mL).

Telbivudine (Tyzeka)

Telbivudine is a nucleoside analogue approved by the FDA for chronic hepatitis B treatment. It inhibits hepatitis B viral DNA polymerase. It is indicated in patients with evidence of ongoing hepatitis B viral replication and either persistent elevated aminotransferase activity or histologic evidence of active liver disease. Consider its use in patients who did not or are unlikely to respond to interferon or for patients who cannot tolerate interferon. Emergence of resistance is major drawback of nucleoside analogue monotherapy.

Class Summary

Hepatitis B vaccine is used for active immunization against disease caused by HBV.

Hepatitis B vaccine, Recombinant (Engerix-B, Recombivax HB)

This vaccine is used for immunization against infection caused by all known subtypes of hepatitis B virus.

Hepatitis A vaccine, inactivated, and hepatitis B vaccine (Twinrix)

This combined hepatitis A–hepatitis B vaccine is used for active immunization of persons older than 18 years against disease caused by HAV and infection by all known subtypes of hepatitis B virus (HBV).