Overcoming Missed Opportunities for Hepatitis Delta Screening and Surveillance

We have very poor prevalence estimates for patients infected with hepatitis delta virus (HDV) in the United States because we don’t test for it as often as we should. We estimate that 15-20 million people in the Western world who have chronic hepatitis B (CHB)—about 5% of people with CHB in this region—are coinfected with HDV. In other parts of the world, HDV prevalence is expected to be much higher. Immigration patterns are changing the epidemiology of HDV in the United States and other Western countries. HDV is a “satellite virus,” dependent on hepatitis B virus (HBV) infection, yet, in studies that have evaluated HDV testing, <5% of patients who are hepatitis B surface antigen (HBsAg) positive also have an HDV test on record. I think we’ve come to understand that there’s a missed opportunity with our current rates of testing and our difficulty in estimating the true prevalence of HDV in the United States and globally.

We should be asking ourselves why testing is so infrequent. Two things likely contribute to this: how we test and whom we test.

How We Test
First, we previously had no accurate tests for HDV. Consistent, validated antibody tests that were shown to be accurate assessments of exposure to HDV were lacking until the past decade—and even then, we did not have an HDV RNA test until recently. So, if you had a patient who had a positive hepatitis delta antibody test, you could not evaluate whether they were viremic.

These tests are now available. Some commercial labs offer them, and this availability provides the first opportunity for us to test our patients and know if a patient who is hepatitis delta antibody positive is also viremic.

Whom We Test
The second contributor to infrequent testing rates is the guidance around whom we should test.  The 2018 American Association for the Study of Liver Diseases (AASLD) guidance says that we should base our HDV screening on known HBsAg positivity, individual risk factors, and country of origin. That’s because we know that in some areas of the world, HDV prevalence is very high. The HDV-infected populations in the United States and Europe are changing based on migratory patterns of individuals from HDV-endemic regions. Risk profiles generally include individuals who are susceptible to percutaneous exposures—usually high-risk sexual contacts or persons who inject drugs, although there are a few other risk factors, as well.

Personally, as a coauthor of the 2016 and 2018 AASLD guidance, my thinking about this testing recommendation has shifted in recent years. The problem is that the list of high-risk countries is not easily accessible when you’re in clinic and seeing a patient, so there is a missed opportunity to evaluate that risk factor.

Based on newer data and guidance from other regions of the world, I’m leaning more toward the idea that every patient who is positive for HBsAg should have a HDV test performed once. I think that’s very important to do, and that’s how we’re going to find the patients with HDV.

If we continue to use a complex algorithm for who should be tested, we’ll inevitably miss testing patients who need it. Universal screening should be the way we move forward with screening for HDV so that we don’t miss out on identifying patients who have it.

The European Association for the Study of the Liver and Hepatitis B Foundation guidelines already account for this, recommending that every patient who is positive for HBsAg should be tested for HDV. I feel like that’s the direction many of the guidance documents are going to go as newer data continue to support this practice to make sure we’re not missing patients with HDV.

Natural History
The main need to improve HDV screening is because patients with HDV have a different natural history than patients with other types of viral hepatitis. We know that patients who are infected with HDV are at higher risk for progressive disease and have higher rates of liver cancer. So, we want to think about their treatment and surveillance differently.

In individuals with HBV, those with HDV are a subgroup of patients who are recommended to undergo hepatocellular carcinoma (HCC) surveillance as soon as the diagnosis is made. But if you’re not making the HDV diagnosis in the first place, you won’t know to have that patient under surveillance. Again, that’s a missed opportunity that we want to overcome by ensuring we’re identifying patients at risk.

Treatment Opportunities
The landscape for HDV treatment is evolving, with 2 drugs in phase III clinical trials—one of which is currently approved in Europe and may soon be available in the United States. The near approval of new HDV treatments provides a strong impetus for us to improve the ways in which we’re identifying patients with HDV—both to make sure they’re getting into surveillance for HCC and to make sure they’re able to access the treatment opportunities that will soon be available for them.

Your Thoughts?
What barriers do you experience in screening your patients with HDV and linking them to care? How are new data influencing your screening practices? Answer the polling question and join the conversation by posting a comment.