Dr. Robert J. Wong is a Clinical Associate Professor of Medicine in the Division of Gastroenterology and Hepatology at Stanford University School of Medicine and a staff physician at the Veterans Affairs Palo Alto Healthcare System. His clinical and research work centers on the epidemiology, outcomes, and health services of chronic liver diseases, with a particular focus on viral hepatitis and on the healthcare disparities affecting underserved and vulnerable populations. He has published extensively on hepatitis delta, including studies on testing rates, prevalence, and the case for reflex-based screening to close the diagnostic gap among people living with hepatitis B.
Q: This past May, the FDA approved the first-ever treatment for chronic Hepatitis Delta virus (HDV) in the United States. What does this milestone mean for patients, how accessible is this new treatment likely to be, and what will it take for the field to fully take advantage of finally having a treatment option?
Having the first FDA approved treatment for patients with HDV infection is an exciting milestone. This approval provides a lifeline for many patients suffering from HDV who now have an effective treatment option. However, awareness remains limited, and many cases of HDV go undiagnosed. Many studies continue to show gaps in implementing HDV screening programs which leads to delays in diagnosis. Hence, while having a new treatment option is encouraging, more work is needed to improve the entire HDV cascade of care, including improved screening and early diagnosis, followed by effective linkage to specialty care who can help coordinate treatment and monitoring.
Q: HepVu’s audience is most familiar with Hepatitis B and C. For those readers, can you explain how Hepatitis Delta fits into that picture — why HDV only occurs in people who already have Hepatitis B, and why that link makes it easy to overlook?
HDV is a defective virus that cannot replicate and infect independently on its own. Instead, the HDV virus relies on the Hepatitis B surface antigen to replicate and infect liver cells. This is why active HDV only occurs in individuals who are already infected with Hepatitis B. This can occur when someone is infected by another individual who has combined HBV/HDV infection, or more commonly, someone with chronic HBV infection is subsequently infected with HDV, termed super infection. Hepatitis Delta is one of the most severe forms of viral hepatitis and is associated with significantly more rapid disease progression to cirrhosis, hepatic decompensation, liver cancer, and liver-related mortality than chronic HCV or chronic HBV monoinfection.
Q: Testing for hepatitis delta is a two-step process that doesn’t happen automatically alongside hepatitis B screening. Walk us through what HDV testing actually involves — the antibody screen followed by the RNA confirmation — and where in that two-step process patients most often fall through the cracks?
Current testing recommendations and diagnostic pathways start with the anti-HDV antibody. However, the anti-HDV antibody alone does not necessarily indicate active HDV infection. It reflects exposure to the virus. Those who have a positive anti-HDV antibody should be subsequently tested for HDV RNA, which reflects active HDV infection. There are several gaps along this diagnostic cascade where patients fall through the cracks. Firstly, many patients with chronic HBV are not routinely tested for HDV. While global guidelines are evolving to recommend HDV testing for all patients with HBV, existing studies show that even “high-risk” patients who have identified risk factors for HDV are not tested effectively. Another step where patients fall off the diagnostic cascade is not completing HDV RNA testing after a positive anti-HDV antibody. Implementing a reflex testing approach (e.g. automatically testing for HDV RNA in the sample blood sample after a positive/reactive anti-HDV antibody result) can help mitigate some of the gaps described.
Q: In your 2025 study published in the Journal of Viral Hepatitis, you found more severe liver disease at the time of presentation among persons newly diagnosed with HDV. What are the reasons for this?
In that study, we evaluated national data from the Veterans Affairs database to analyze HDV testing practices and outcomes. We observed major gaps in testing with the vast majority of adults with chronic HBV having not undergone HDV testing. Furthermore, we observed that among adults with HDV diagnosed, nearly 1 in 3 patients had already developed cirrhosis, hepatic decompensation, or liver cancer. This reflects delays in timely diagnosis of HDV, such that patients have already developed progressive and advanced disease by the time the diagnosis is made. Now that we have approved therapies, it is critical to focus efforts to improve early identification of HDV so that these patients can be linked to effective therapies to prevent disease progression and cirrhosis-related complications.
Q: In 2024, you and your colleagues published an article in the Journal of Viral Hepatitis which evaluated a universal approach to HDV testing among veterans with chronic hepatitis B virus infection as opposed to the current recommendations which recommend HDV testing based on a history of risk. What did you learn from that study?
In that study, we performed a pilot study to test all consecutive patients with chronic HBV for HDV in our outpatient hepatology clinic. In total, 91 patients were offered anti-HDV testing, among whom 70 completed testing. Among those 70 patients, 3 (4.3%) were positive for anti-HDV. HDV RNA was ordered in all 3 anti-HDV positive patients, but only 2 completed HDV RNA. One patient was found to be positive for HDV RNA. Our findings emphasize that even by implementing a universal testing approach, separate laboratory visits for anti-HDV testing and HDV RNA testing contributed to potential barriers leading to patients falling off the diagnostic cascade of care. As mentioned earlier, implementing true integrated reflex testing approaches could mitigate some of these challenges.
Q: Now that there is an approved therapy for HDV, if you could change one thing about how the U.S. currently approaches HDV testing and linkage to care, what would it be? And what should public health audiences and providers reading HepVu take away about closing the testing gap?
I think we need to improve current HDV testing and linkage to care. I believe that universal testing for HDV would improve timely diagnosis and linkage to care. We have learned from the history of HIV, HCV, and even HBV testing that risk-based approaches too often fail. Moving to a universal testing approach would also reduce the stigma associated with targeted testing of “high risk” individuals. Recent data have shown one-time HDV testing in all chronic HBV patients to be a cost-effective approach. However, diagnosis is only the first step in the care cascade, and we need more novel interventions to improve patient outreach to re-engage them back into care for monitoring and treatment. Rarely is there a one-size fits all approach, and I think successful programs for HDV testing and linkage to care will need to tailor it to the specific challenges and needs of the community being cared for.
