Why Hepatitis B and Hepatitis C Cures Are Fundamentally Different

This episode, "Why Hepatitis B and Hepatitis C Cures Are Fundamentally Different," features the panel examining why hepatitis B's viral integration sets it apart from hepatitis C.

Dr. Chung asks Dr. Dieterich to compare hepatitis B and hepatitis C, and to explain why the hepatitis B functional cure story differs fundamentally from the hepatitis C cure story that clinicians and payers already know.

Dr. Dieterich explains that hepatitis C is a flavivirus, a family in which no other member, including dengue or yellow fever, ever becomes chronic. Once a patient is cured of hepatitis C, the virus does not integrate into the genome and stays confined to the cytoplasm, so clearance is truly permanent. He notes that liver cancer can still emerge in cured hepatitis C patients who had cirrhosis, but that risk stems from pre-existing cirrhotic damage, not any remaining virus.

Hepatitis B behaves very differently, he says, describing it as closer to HIV, sometimes called a closet retrovirus because it cycles from DNA to RNA and back to DNA, integrating into the hepatocyte genome. That integration means the virus is never completely eliminated, even once surface antigen clears. He mentions that therapies aimed at de-integrating hepatitis B DNA from cccDNA and the hepatocyte genome exist but are not yet ready for clinical use. Because integrated DNA persists, it can continue stimulating oncogenes or suppressing tumor-suppressor genes even after antigen loss.

Dr. Chung summarizes that functional cure means losing surface antigen and reducing clinical endpoints, but it does not represent a true virologic cure. He stresses that clinicians must remind patients and referring providers that the virus can still return through reactivation, since it never fully leaves the body the way hepatitis C does once cured.

Our next episode, "The Next Frontier in Hepatitis B Functional and Virologic Cure," turns to the pipeline of therapies aiming to push cure rates even further.