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Professor of Medicine
Chief, Section of Hepatology
Associate Director, Solid Organ Transplantation
Richard B. Capps Chair of Hepatology
Rush University Medical Center
Nancy Reau, MD: consultant: AbbVie, Arbutus, Gilead Sciences, Intercept, Salix; researcher (paid to her institution): AbbVie, Gilead Sciences.
There were many exciting viral hepatitis studies presented at the 2022 International Liver Congress (ILC), the annual meeting of the European Association for the Study of the Liver (EASL). We saw practice-changing advancements in treatment and monitoring strategies for hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV).
Novel Therapeutics for HBV
There are numerous novel compounds currently in phase II trials for the treatment of HBV. Based on this, both healthcare professionals (HCPs) and patients hope to see the same “explosion” in highly efficacious treatment options and short-term cure for HBV as we did a few years ago for HCV. We have not yet seen that for HBV, but for context, it did take a long time for us to get curative, short-duration therapies for HCV. We should remember that HBV and HCV are mechanistically different viruses.
Several mechanistically unique compounds described at ILC 2022 look attractive for the treatment of HBV. Small interfering RNA molecules are effective at decreasing hepatitis B surface antigen (HBsAg) levels. There was a polymerase inhibitor that showed virtually no risk of viral flare after treatment discontinuation. Nucleic acid polymers and capsid assembly modulators are new mechanisms and are attractive as combination therapies.
Of importance, many of the compounds for HBV had strong safety and efficacy data in their phase II trials that allow them to progress to phase III trials. We cannot forget that drug development for something that is safe and efficacious is indeed slow—but we are seeing progress.
Emerging Therapeutics for HDV
We continue to get more data that bulevirtide—which is soon to be approved in the United States and is available via conditional access in many other parts of the world—continues to show good efficacy and safety for the treatment of patients with HDV. Bulevirtide has good antiviral effect, which seems to be cumulative. As we move beyond 6- and 12-month treatment durations, there are signals that the use of bulevirtide is improving liver fibrosis and stiffness markers. Hopefully, this will translate into a reduction in clinical events in the long term. In addition to bulevirtide, we also saw a few studies on lonafarnib and peginterferon-λ, so there are more agents in the HDV pipeline that we should keep an eye on. We cannot forget that any time we see something in the HBV pipeline that might affect HBsAg or eliminate HBV, it will ultimately translate toward treating HDV.
Therapeutic Vaccination for HBV
There is a difference, however, between a therapeutic vaccine and a vaccine that is meant to prevent infection. Data presented at ILC 2022 revealed some exciting therapeutic vaccines for HBV that augment immune recognition. When we talk about HBV functional cure, there is not only an antiviral strategy, but also an immune modulatory strategy, and some people think that patients will need the combination of antiviral agents plus immune augmentation. The good news is that several of these therapeutic vaccines do both. We think that by triggering immune recognition and overcoming immune tolerance, functional cure is achieved.
Monitoring for HCC After HCV Cure
HCV is still associated with significant morbidity and mortality worldwide. Although we have excellent HCV therapies available, data presented at ILC 2022 reminded us that the HCV care cascade is falling apart in multiple places. We still lack HCV screening and linkage to care. There are many gaps in the steps before engaging a patient in treatment, but once you get a person diagnosed with HCV on treatment, the efficacy is excellent, and we expect that person to be cured.
At ILC 2022, other studies explored assessing patients following HCV cure. This is important because these patients continue to have residual risks even after cure, especially for hepatocellular carcinoma (HCC). The risk of HCC increases over time, so although HCV curative therapy decreases a person’s HCC risk monumentally, the risk still exists long term. We want to ensure that we identify patients who need to continue HCC screening and engage them in longitudinal surveillance. I think we do not yet have a perfect model that allows us to identify and exclude a patient at low risk who has cirrhosis. However, patients who have advanced fibrosis should be engaged in longitudinal care because their history of HCV continues to drive HCC rates. Similar to our patients with HBV and HDV, we want to monitor and identify HCC early in our patients with current or previous HCV. Our HCC treatments are most efficacious in patients who are diagnosed at early stages.
What do you think were the most exciting viral hepatitis data presented at ILC 2022? Join the discussion by posting a comment. For more details on this and other key viral hepatitis issues from EASL 2022, review more CCO Conference Coverage, including video and audio recaps with expert faculty.