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HDV Management in the US
Your Patient Is Diagnosed With Hepatitis Delta Virus—Now What?

Released: March 11, 2024

Expiration: March 10, 2025

Robert Wong
Robert Wong, MD, MS
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Key Takeaways
  • Early HDV diagnosis is key to implementing appropriate treatment and monitoring.
  • After HDV is diagnosed, healthcare professionals should evaluate the need for HBV treatment, closely monitor for hepatocellular carcinoma, and assess treatment options for both HBV and HDV.
  • Pegylated interferon-alfa is currently the only recommended treatment for HDV, but use of emerging investigational therapies may be considered through compassionate use programs or clinical trials.

Hepatitis delta virus (HDV) acquisition occurs in the setting of concurrent hepatitis B virus (HBV) and is associated with more rapid liver disease progression to cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease. However, suboptimal awareness of HDV has contributed to undertesting and underdiagnosis. In the United States, it is estimated that 50,000-100,000 individuals may have HDV—many of whom remain undiagnosed.

Screening and Diagnosis
In patients with HBV, early diagnosis of concurrent HDV is critical so that appropriate monitoring and treatment for both viruses can be implemented quickly. 

Initial evaluation for HDV includes testing for anti-HDV antibody. However, existing data suggest that only 50% to 70% of patients with positive anti-HDV antibody have viremic HDV, which is characterized by detectable HDV RNA. Hence, it is important to ensure that patients with positive anti-HDV antibody get appropriate follow-up testing for HDV RNA to evaluate for active HDV. If patients are positive for anti-HDV antibody but negative on HDV RNA testing, routine periodic testing for HDV RNA is recommended for those with continued risk factors for HDV acquisition.

After your patient is diagnosed with HDV, what’s next? Here I discuss my approach to managing patients with HDV.

Address HBV
I start by addressing the patient’s HBV. I initiate HBV antiviral therapy in all my patients with concurrent HBV and HDV who have any detectable HBV DNA. This aligns with recommendations from the American Association for the Study of Liver Diseases: Patients who do not meet criteria for HBV treatment but who have evidence of concurrent HDV and elevated HBV DNA should promptly initiate first-line HBV antiviral therapy with either entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide. 

Perform HCC Surveillance
Closer surveillance for HCC also is warranted in patients with HDV, given the higher risk of developing HCC compared with those with HBV alone. An abdominal ultrasound and α-fetoprotein laboratory monitoring should be completed every 6 months for HCC surveillance. I perform HCC surveillance for all my patients with concurrent HBV and HDV regardless of whether they have cirrhosis.

Assess for HDV Treatment 

PegIFN
In the United States, no therapies for HDV are approved by the FDA. Based on expert guidance, pegylated interferon-alfa (pegIFN) for 12 months is still the only recommended treatment at this time for HDV in patients with elevated HDV RNA and elevated alanine aminotransferase. However, pegIFN should be used with caution given its safety profile and the limited long-term efficacy in successful treatment of HDV.

Personally, given the novel, more effective, and safer HDV therapies on the near horizon, I currently do not routinely use pegIFN to treat all my patients with HDV. My approach depends on their severity of disease and is summarized below.

  • Patients with decompensated cirrhosis: I avoid the use of pegIFN and refer these patients for liver transplantation evaluation, if appropriate.
  • Patients with compensated advanced disease (eg, advanced fibrosis or compensated cirrhosis): I have more urgency to treat HDV to halt disease progression, and for these patients I tend to favor treatment with pegIFN with close monitoring. I have a thoughtful discussion regarding the pros and cons of pegIFN treatment and the expectation of potential novel therapies on the near horizon. 
  • Patients with earlier-staged disease: Although treatment is equally important, my urgency to treat them is less, and these are situations where waiting for more effective and safer therapies on the horizon may be prudent. 

Bulevirtide and Other Investigational Agents
Bulevirtide is a novel therapy for HDV that has been authorized for use by the European Medicines Agency. It is undergoing review by the FDA for the treatment of patients with HDV, and expanded access to bulevirtide may be available in certain situations through a compassionate use program.

Referral to or coordination with a regional center of excellence or academic medical center is recommended to guide HDV treatment decisions, including potential compassionate use of bulevirtide and use of other investigational agents through ongoing HDV clinical trials.

Your Thoughts?
How do you approach managing patients with HDV? Join the discussion by posting a comment.