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Researchers provide updated HBV treatment algorithm

A panel of U.S. hepatologists convened and provided recommendations for updating the treatment algorithm for hepatitis B virus infection, according to a treatment report published in Clinical Gastroenterology and Hepatology.

“The goal of the revised algorithm is to provide health care providers with the most current information on the screening, diagnosis and treatment of [chronic hepatitis B],” the researchers wrote.

Using data from scientific and medical literature, their own experiences and expert opinion, the panel, which included HCV Next Co-Chief Medical Editor Ira M. Jacobson, MD, chair of the Department of Medicine at Mount Sinai Beth Israel Medical Center and co-director of the Liver Institute at Mount Sinai Health System, New York, and HCV Next editorial board member Douglas T. Dieterich, MD, professor of medicine, division of liver diseases, director of continuing medical education, Icahn School of Medicine, Mount Sinai, New York, provided new recommendations that addressed the following issues: establishing which patients should be candidates for antiviral treatment; the advantages and disadvantages of available treatment options; when a clinician should initiate treatment; when and if treatment should be discontinued; whether or not on-treatment monitoring is necessary; and, which strategies should be used by clinicians to decrease any risk for antiviral resistance.

Ira M. Jacobson

Candidates for Treatment

The researchers stated that deciding to treat or not treat a patient for HBV should no longer be based solely on elevated alanine aminotransferase levels.

“There is a lack of strict correlation between the extent of liver cell necrosis and the degree of increase in ALT, which means that ALT alone does not identify patients with necroinflammatory activity or fibrosis with optimal reliability,” the experts wrote.

The panel recommends that ALT levels of 30 IU/L for men and 19 IU/L for women be the upper limit of normal when deciding to initiate therapy. In patients who are positive for hepatitis B e antigen (HBeAg) with HBV DNA levels greater than 2,000 IU/L and normal ALT levels, a liver biopsy or transient elastography should be considered. These patients, as well as those negative for HBeAg with ALT levels greater than 2,000 IU/L and elevated ALT without fibrosis can be considered for treatment. However, if they do not meet these requirements, HBV DNA and ALT levels should be monitored every 3 to 6 months. Patients with HBV DNA greater than 2,000 IU/L, elevated ALT levels and any level of fibrosis should be treated.

The panel also recommends serial testing of HBV DNA be performed via a sensitive real-time polymerase chain reaction-based assay, to assist a clinician in determining the viral threshold for treatment.

Current Therapies

According to the panel, there are currently seven medications available for managing chronic HBV in the U.S.: interferon alfa-2b, peginterferon a-2a, Epivir (lamivudine, ViiV Healthcare), Hepsera (adefovir, Gilead Sciences), Baraclude (entecavir, Bristol-Myers Squibb), Tyzeka (telbivudine, Novartis) and Viread (tenofovir disoproxil fumarate, Gilead Sciences).

Of these drugs, the preferred first-line treatment choices are entecavir and tenofovir based on their efficacy and resistance profiles, according to the panel.

“For nearly all HBV patients, monotherapy with entecavir or tenofovir is the appropriate first-line treatment because both have potent antiviral activity and high barriers to resistance,” the researchers wrote.

Among treatment-naive patients, a regimen of PEG–IFN-a, entecavir or tenofovir is recommended. Patients with a history of lamivudine use should not receive entecavir due to the risk of amino acid substitutions for lamivudine resistance that could potentially create entecavir resistance. See the full report for more information on specifics of the individual drugs and the effects of switching therapies.

Douglas T. Dieterich

Treatment Recommendations

“The two main treatment strategies for both HBeAg-positive and HBeAg-negative [chronic HBV] are either 1 year of treatment with peginterferon or long-term therapy with a nucleoside or nucleotide analogue,” the panel wrote.

Among patients positive for HBeAg, the panel recommends the following: patients with HBV DNA levels greater than 2,000 IU/mL and elevated ALT levels should be treated with the first-line option of PEG-IFN a-2a, entecavir and tenofovir. Patients with a history of lamivudine use should not receive entecavir therapy and lamivudine and adefovir are not recommended as first-line treatments. For the use of nucleoside and nucleotide analogues, lifelong therapy is recommended in those with decompensated cirrhosis and those with stages F3 or F4 fibrosis at the start of therapy.

In patients negative for HBeAg, the panel recommends PEG-IFN a-2a, entecavir and tenofovir as first-line treatment and that liver fibrosis assessment be performed at baseline before therapy. Lamivudine, adefovir and telbivudine are not recommended as first-line treatment. Patients should be monitored every 3 to 6 months and PEG–IFN-a should be given only for 12 months. For the use of nucleoside and nucleotide analogues, lifelong therapy is recommended in those with decompensated cirrhosis and those with stages F3 or F4 fibrosis at the start of therapy. Patients who stop therapy should be monitored and those who relapse can be retreated.

On-Treatment Monitoring

All HBV DNA levels should be monitored at 12 weeks of therapy and at 24 weeks to confirm virologic suppression is still apparent. After 24 weeks, HBV DNA levels should be monitored every 3 to 6 months during the first year of treatment. Any patient who does not respond to nucleoside or nucleotide analogues after 12 to 24 weeks of treatment should be evaluated for compliance, according to the panel, due to the fact a nonresponse to treatment is considered rare. Patients with a partial response or inadequate virologic response at 24 weeks or who have positive HBV DNA at 48 weeks should also be evaluated for compliance. See the full report for more information on patients who fail to meet a virologic response or meet virologic resistance during treatment.

Looking to the Future

Despite various treatment options, the panel recognized the fact that barriers to treating this infection still exist.

“Although there have been any advances in the treatment of [chronic HBV] in recent years, several unmet needs exist,” the panel wrote.

Examples of these unmet needs include: the need for more data on the duration of therapy for nucleoside and nucleotide analogues; management of immunotolerant patients; the role of hepatitis B surface antigen quantification in evaluating response to therapy; and finding more patients with HBV.

The panel concluded: “On a positive note, research is rapidly expanding in the area of curing HBV, with a variety of promising agents in clinical trials now. The next time this algorithm is revised, there may be many ways to treat and even cure HBV.” – by Melinda Stevens

Disclosures: Please see the study for a full list of all authors’ relevant financial disclosures.