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Applying New EASL Data and Guidelines to Our Patients With HDV

Released: August 11, 2023

Nancy Reau
Nancy Reau, MD
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Key Takeaways
  • To highlight the growing understanding on the importance of HDV/HBV coinfection, EASL issued its inaugural on screening, diagnosis, and management of these persons.
  • Recommendations are straightforward and should clarify management of these patients.

Hepatitis D virus (HDV) is a defective virus that requires the hepatitis B virus (HBV) to complete its life cycle. Although the least common viral hepatitis, it is the most aggressive, leading to severe liver disease and liver cancer in those chronically infected and higher rates of acute liver failure in acute infection. Our understanding of this infection’s life cycle has evolved in recent years, and new data may help us to manage this infection more readily.

The EASL 2023 International Liver Congress provided healthcare professionals (HCPs) with both updated clinical data to help guide HDV management and EASL’s inaugural Clinical Practice Guideline on the identification, virologic and clinical characterization, prognostic assessment, and appropriate clinical and therapeutic management of individuals infected with HDV. 

What Can HCPs Take Away From the EASL 2023 and the Guideline?

1. Screening by measuring HDV antibody should now be universal in all persons positive for hepatitis B surface antigen (HBsAg).

 Earlier recommendations had concentrated on at-risk groups, including demographics or high-risk behaviors. This recommendation was always a challenge to implement.

The current recommendation is clearer: Is your patient HBsAg positive? Order an HDV-Ab.

That being said, screening should still be done in the case of unexplained flare, acute decompensation, or chronic liver disease, or in those at risk for HDV infection. In other words, the traditional screening model is still important, even in an individual who was tested for HDV in the past and was negative. [CODER: https://clinicaloptions.com/CE-CME/hdv-screening/1000013162]

2. Diagnosis must include measuring HDV viral load.

Similar to HCV infection, antibody testing for HDV only demonstrates exposure and not active infection. If your patient has tested positive for HDV-Ab, the next step is to measure HDV RNA. Unfortunately, for HDV, this does not automatically occur in most laboratories (as it does for hepatitis C virus), so screening and diagnosis remain a 2-step process.

3. To guide management, a liver biopsy may be recommended.

HDV/HBV coinfection is much more aggressive than HBV monoinfection. As a consequence, staging is imperative even in our younger patients.

The new guidelines still advocate for the use of noninvasive testing (NIT) in the HDV population, but the language used in the guidelines is cautionary. NIT has not been well validated in HDV, and biopsy data from the lonafarnib trial suggest that advanced disease could be missed by using NITs alone. This is especially concerning as more than 40% of the trial participants with cirrhosis were 45 years of age or younger. The guidelines urge HCPs to consider a liver biopsy when knowledge of liver histology would change management.

It is also important to try to modify any factor that may increase the risk of progression—that is, treat and cure HCV, control HBV, and counsel regarding obesity, diabetes management, and alcohol use. Even if your patients are not receiving HDV therapy, they should be closely monitored with assessment every 6-12 months.

4. All persons with HDV infection should be treated.

The guidelines strongly advocate for therapy for all patients with active HDV infection. However, therapeutic choices (and patient enthusiasm for the prospect of treatment) may depend on available options. If your patient has decompensated liver disease, transplant is always the preferred route. However, management options are not so obvious for our patients with less severe diseases.

Some countries have access to bulevirtide, which absolutely should be considered in those with advanced disease and can be considered for those with less severe injury. Data presented at EASL 2023 showed excellent virologic response and safety in those who received either 2 mg or 10 mg daily.

Data from a trial of ritonavir-boosted lonafarnib with or without peginterferon-α were also presented at EASL, which showed histologic improvement in 33% to 53% of patients on therapy.

If these agents are not available, peginterferon-α has been used for HDV for decades and should be considered in HDV-infected individuals with compensated liver disease.

5. Liver cancer screening by ultrasound is recommended in all persons with HDV and advanced disease.

Screening for liver cancer is also recommended for persons who are HBsAg positive and without advanced disease. Women should start screening at 50 years of age and men at 40 years of age.

Your Thoughts?

Do these guidelines clarify steps of screening, diagnosis, management, and surveillance for you? Let us know how you’re applying them in your practice by joining the conversations below.