Does this mean a partial cure?

General Discussion
#1

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@ThomasTu @availlant @everyone
Fibro scan is normal according to doctor
Does this mean a partial cure?

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#2

Dear @Godsown ,

The definition of partial cure is HBV DNA < 2000 IU/mL with normal ALT for aleast 6 months after removal of all antiviral therapy. Fibroscan is not part of this definition but it is good news that it is normal. Are you currently off therapy? What is your HBV DNA?

Best regards,

#3

HBsAb …negative

what do you all say?
could it mean different things?

#4

Hi @catcher.007 ,

The presence of HBsAb or not is not required for functional cure. In a prophylatic setting, the presence of HBsAb indicates protection from infection. However, as recent studies with therapeutic vaccines and NAPs have shown, the appearance of HBsAb during therapy does not constitute protection. This is because HBsAg persists which is not recognized by this HBsAb (immune escape HBsAg).

Best regards,

#5

So, how does this work exactly? Let’s say a person gets infected in his/her childhood - as the years pass, this person will have some (more and more?) immune escape HBsAg.

Then, this infected person has blood or other bodily fluid contact with a healthy, vaccinated person who has antibodies generated by the vaccination. Will these antibodies protect against immune escape HBsAg from the infected person? Setting a bit similar to older COVID vaccines, which no longer protect against recently mutated SARS-CoV-2 variants and needed a vaccine update?

#6

HI @mantana ,

A good question for a complicated issue - why does vaccination work to protect from infection when different HBsAg species are present in the virus which is shed by an infected person?

As we have discussed elsewhere in the forum (see here), HBV infection in any one person is actually a pool of HBV genome variants (which I previously termed quasispecies). Actually, John Tavis and I have chatted about this offline and we agree that this term is not correct (even though used widely in the literature) since these genome variants do not contain mutations which are linked to each other (so behaving like genetically conserved species) but are instead generated randomly and enriched from selection pressure by the immune system or some antiviral therapies.

So over the course of HBV infection, the prevalence of genome variants (and the HBsAg variants they generate) evolves according to the immune selection pressure from the infected person’s immune system. Fortunately, MOST of these variants will still be recognized by antibodies produced from standard vaccination. So vaccination still effectively prevents the development of infection from this viral innoculum.

Now in a person with already established infection, the pool of immune escape HBsAg is already well entrenched and can evade the vaccine response. This is why therapeutic vaccination has failed to date in all clinical trials to achieve functional cure (despite the production of strong vaccine responses).

This is different from the situation with SARS CoV2 (and influenza) where the entire viral innoculum can be entirely immune escape against a particular vaccine.

Best regards,

#7

Before this test I was not on therapy, it’s more than six month between when I was diagnosed and when I did this test.I couldn’t afford HBV DNA test (viral load) as at then. @availlant