Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published July 5, 2023


Are there any approved therapies for chronic hepatitis D in the United States?

The risk of cirrhosis and hepatocellular carcinoma is higher among patients with hepatitis D virus (HDV) infection than among those with hepatitis B virus monoinfection. Read the NEJM Review Article here.

Clinical Pearls

Q: Is there a link between HDV and hepatitis B virus (HBV)?

A: HDV, also known as hepatitis delta virus, is a defective, hepatotropic pathogenic agent. The life cycle of HDV requires the hepatitis B surface antigen (HBsAg) provided by HBV. Like HBV, HDV is transmitted by the parenteral route through infectious body fluids; intravenous drug users are at highest risk for infection because of contaminated syringes. Clinical studies have shown that chronic hepatitis D is the most severe and progressive form of viral hepatitis in humans.

Q: Has the prevalence of HDV infection changed in recent decades?

A: The prevalence of hepatitis D has changed in the past 25 years, reflecting the control of HBV infection afforded by the worldwide implementation of HBV vaccination programs. These programs are reducing the number of HBsAg carriers who are susceptible to HDV and, as a secondary effect, are contributing to the global decline of HDV infection. The burden of HDV infection remains high in Moldova and in many African and Asian countries where the percentage of HBsAg carriers in the population is high.

Morning Report Questions

Q: What is the current status of screening for HDV?

A: Recommendations from international associations differ regarding anti-HDV antibody screening. The European and Asian Pacific Associations for the Study of the Liver recommend testing for anti-HDV antibodies in all HBsAg-positive persons, whereas the American Association for the Study of Liver Diseases recommends such testing only in high-risk patients, including those who have immigrated from countries where HDV is endemic. HDV screening remains low in both developed and developing countries. Of 157,333 patients with chronic hepatitis B in the United States between 2010 and 2020, only 6.7% underwent HDV testing. One strategy to increase HDV screening is reflex testing for anti-HDV antibodies in all persons who test positive for HBsAg. This would prevent health care providers who are not familiar with hepatitis D from overlooking a diagnosis of HDV infection. Implementation of reflex testing recently led to an increase by a factor of 5 in the number of HDV diagnoses in Spain.

Q: Are there any approved therapies for chronic hepatitis D in the United States?

A: There is no approved therapy for chronic hepatitis D in the United States. Although pegylated interferon alfa has been used off label, in accordance with the recommendations of major liver societies, data on the results of this use are limited. Tenofovir or entecavir has been added to therapy for HDV in some studies in order to prevent possible reactivation of HBV after the inhibition of HDV. Targeting HBV with antiviral agents (lamivudine, adefovir, entecavir, or tenofovir) is of no avail in controlling HDV infection. These agents inhibit the replication of HBV DNA but do not interfere with the synthesis of HBsAg, which is necessary for HDV. Preliminary data indicate that bulevirtide can control the disease in more than half of patients. Bulevirtide was conditionally approved by the European Medicines Agency in July 2020; it is not yet available in the United States. Other new drugs for the treatment of HDV infection are currently under investigation. Combination therapy with these agents, possibly administered with newly developed inhibitors of HBsAg synthesis, holds promise as a cure for chronic hepatitis D.

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