Hepatitis D is a liver disease that affects roughly 12 million people worldwide. It’s only present in people who are already infected with hepatitis B, because it needs antigens from hepatitis B, called HBsAg, to attack the liver.
And when a person with hepatitis B contracts hepatitis D, it’s bad news. Hepatitis D dramatically accelerates liver damage and the patient progresses faster towards liver failure, cancer and death.
Up until recently, there was only one treatment option for hepatitis D. Called pegylated interferon α (PEG-IFNα), it didn’t have the best track record, only eliminating hepatitis D in 20-30% of cases and causing severe side effects. Frequently, those who were treated with PEG-IFNα relapsed.
Recent years have brought more hope to people with hepatitis D. A new drug called bulevirtide is showing a lot of promise, but predicting which patients will respond best to the drug remains a challenge.
The VIROMARKERS project is trying to dig deeper into how hepatitis D works, so that better biomarkers can be developed and the people who will benefit most from bulevirtide can be easily identified.
What a new study conducted by the VIROMARKERS project found was that people with chronic hepatitis D showed significantly higher levels of different forms – known as isoforms – of HBsAg compared to those people with only hepatitis B.
Further analyses showed that high levels of small and medium HBsAg isoforms were associated with better replication of Hepatitis D. These isoforms might serve as useful biomarkers for identifying patients who are most likely to benefit from bulevirtide therapy.
What’s more, these HBsAg isoforms showed a positive correlation with high levels of a protein found in the liver called alanine aminotransferase. Healthy people have low levels of alanine aminotransferase circulating through their blood, but high amounts of alanine aminotransferase indicate liver inflammation. This result suggests that there may be a connection between high levels of HBsAg and liver inflammation.
According to Valentina Svicher, last author of the study and professor of virology at the University of Rome Tor Vergata, these results highlight the potential of isoform profiling to demystify hepatitis D and develop new solutions for patients.
“Our vision is to establish HBsAg isoform profiling as a novel and scalable precision-medicine tool for chronic hepatitis D, bridging virology, biomarker discovery, and clinical practice to improve patient stratification, accelerate therapeutic innovation, and reduce the burden of advanced liver disease across Europe and beyond,” she says.