Q&A: The challenges of curing hepatitis B
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SEATTLE — The effort to find a cure for hepatitis B faces steep challenges, Anna Suk-Fong Lok, MD, told Healio after her plenary presentation at the Conference for Retroviruses and Opportunistic Infections.
Lok, the assistant dean for clinical research and Alice Lohrman Andrews Research Professor of Hepatology at the University of Michigan Medical School, said that although there are promising treatments in the pipeline, the concept of a “cure” for HPV may need to redefined.
Lok told us what she thinks the priority areas of research should be to move closer to a cure.
Healio: Why is there a cure for hepatitis C but not hepatitis B?
Lok: They are different viruses and different diseases. Direct-acting antiviral agents (DAAs) for HCV do not work for HBV.
Healio: How would you define an HBV “cure”? What would it look like?
Lok: Ideally, we would like to eradicate the virus but currently our definition [is] functional cure defined as sustained hepatitis B surface antigen (HBsAg) loss with undetectable HBV DNA 24 weeks after completing a finite course of treatment.
Healio: Have discoveries been made in recent years that make a cure for HBV more possible?
Lok: Many new antivirals and immune modulatory therapies are in development. Some have shown safety and promising results in clinical trials, and a couple are moving into phase 3 trials. Antivirals are ahead of immune modulatory therapies, and the front-runners are [small interfering RNAs/antisense oligonucleotides] and capsid assembly modulators. Almost all are used in combination with [nucleos(t)ide analogues] and a few with [interferons].
Healio: Based on progress and discoveries in recent years, what are the areas of research you think should be a focus to move closer to a cure for HBV?
Lok: The focus for future work to cure HBV should be on identifying which DAAs to combine to inhibit HBV DNA replication and to shut down HBsAg production. The latter will require finding a method to eliminate or silence integrated HBV DNA transcription in addition to silencing [covalently closed circular DNA] transcription.
It is also important to determine which patients will have immune recovery after virus replication and viral antigen production are shut down and which ones will require immune modulatory therapy to enhance or restore immune responses and how to tailor immune modulatory therapy according to the individual’s immune responsiveness to HBV. Additionally, it is important to determine if HBV cure as currently defined is feasible or if an intermediate step of partial cure — sustained off therapy HBsAg of less than 100 IU/mL and HBV DNA undetectable after a finite course of treatment — is needed in the short term.
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