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Screening for HDV in CHB
Why I Screen for and Treat Hepatitis Delta Virus

Released: March 29, 2023

Heiner Wedemeyer
Heiner Wedemeyer, MD
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Key Takeaways
  • HDV infections are treatable, but first they must be identified.
  • The Hep B Consult tool can be used to increase HDV screening and guide treatment in patients with chronic hepatitis B. 
  • Reflex and double reflex testing by healthcare systems can facilitate HDV screening

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis, with a high risk of developing complications of liver disease and hepatocellular carcinoma. In fact, 2 systematic reviews showed that HDV infection is associated with a higher incidence of hepatocellular carcinoma.

Considering the severity of the disease and the availability of treatment options to prevent disease progression, it is time to increase our efforts to identify patients with chronic hepatitis B (CHB) living with HDV infection. 

New Treatments for HDV
In Europe, 2 treatments are available: pegylated interferon alfa (pegIFN-alfa) and the entry inhibitor bulevirtide.

Dr Lisa Sandmann and I recently summarized the mechanism of action, treatment efficacy, and long-term clinical outcomes of trials published on interferon treatment of HDV. Approximately 25% to 33% of patients who received an interferon-based regimen maintained an off-treatment virologic response, which translates into a reduced risk of developing complications of liver disease. Of importance, we also highlighted that pegIFN-alfa very likely will be part of future treatment regimens, even after approval of newer drugs for HDV. 

Bulevirtide received conditional approval as an HDV treatment in Europe in July 2020. A recently published pivotal phase II study evaluating treatment with bulevirtide in combination with tenofovir disoproxil fumarate supports use of this treatment regimen. In another study, nearly 75% of patients experienced a profound virologic response, with an HDV RNA decline of at least 2 log IU/mL when receiving bulevirtide with or without pegIFN-alfa. The safety and efficacy of bulevirtide was confirmed by real-world studies, as well.

Increasing HDV Screening
Considering these developments in the treatment of HDV, the first step is identifying individuals infected with HDV. This is a particular challenge, as HDV infection is a rare disease. Moreover, HDV infection can be found in distinct at-risk groups (eg, migrant populations, people who inject drugs) with limited access to healthcare.

A simple solution to detect HDV coinfection may be to implement automated reflex testing for anti-HDV antibodies in people who are hepatitis B surface antigen positive. In an ideal scenario, automated double reflex testing should be performed where anti-HDV antibody‒positive samples are then automatically tested for HDV RNA. Reflex testing strategies currently are being evaluated in different countries with good results. 

Summary
HDV infection is treatable—but it must be identified to be treated. It is very likely that available treatments reduce the risk of clinical complications in most patients. Therefore, I consider it our ethical responsibility to increase efforts to identify individuals at risk.

One approach is a simple app, the Hep B Consult tool, which can help prompt HDV testing and guide treatment for patients who test positive. It includes HDV screening questions and HDV treatment recommendations to raise awareness among healthcare professionals to consider HDV screening (and subsequent treatment if indicated) in their patients with CHB.

Another approach is simple diagnostic algorithms that can be implemented in healthcare settings.

Still, additional studies are needed to confirm cost efficacy and to identify groups of patients for whom double reflex testing may be particularly useful. Automated algorithms, possibly with the help of artificial intelligence, should be implemented considering country- and setting-specific factors. 

Your Thoughts?
What are your strategies to ensure that all of your patients with CHB are screened for HDV? Join the conversation by posting a comment below.