Functional “Cure”

From reading different articles on Hep B, a person has achieved immunity from natural infection if the test result is HBsAg(Negative), anti-HBc(Positive), anti-HBs(Positive)
However, I recently came across an article in Hepatitis B Foundation in which it attributes the following to Dr. Robert Gish, “if people have an undetectable viral load, undetectable HBsAg, and no signs of liver damage, they may be “functionally cured,” even if they haven’t developed surface antibodies. He further states that the same result will have to be achieved for two or more years(I am assuming that undetectable HBsAg is the same as a Negative HBsAg)
Is this statement widely accepted by other experts in the Hep B community?

The following is my result received on March 29, 2022
HBcAB is Positive
HBsAg is Negative
HBsAb is Negative
HBV Load PCR is Not Detected
ALT is 28
AST is 18
My Blood Cell Count and Blood Cell Review are all within normal range

If i am able to maintain my numbers for 3-5 years, will i be considered ‘functional cured?’
Also, is there a direct relationship between the ALT/AST numbers and Liver health(at least, it gives the preliminary indication of what is going on with the Liver?)

Thank you.

Dear @Yaoman,

Thanks for your question. Your understanding is correct and I believe generally accepted in the community. An additional caveat is that the concept of a functional cure is left mostly for when you have a chronic infection (so more than 6 months) and you lose HBsAg afterwards.

If you only have these results, there are different possibilities than could have led to this, including:

  1. You have had a chronic infection, cleared the infection, and are functionally cured. You may indeed have no HBsAb developed yet.
  2. You have been exposed earlier in life, had an acute infection, cleared the virus, and your HBsAb levels have waned.
  3. The HBcAb is a false positive and you have not been exposed to HBV or vaccinated against HBV.

I would think that ongoing discussion with your doctor and additional blood tests could help figure out what has happened.

That said, in the majority of cases, being HBV DNA and HBsAg-negative is a really good sign that is linked to positive outcomes and is generally a stable state. So I think it would be safe to be optimistic.

Thomas

Hi Thomas,

I was reading this new thread and it has piqued my interest. I have been diagnosed with a chronic but inactive HBV infection with a negative for the surface antigen in my bloodwork so from my current understanding of your explanation I would like to fully grasp this concept of “functionally cured”. However, I am a permanently exhausted pigeon, and despite reading and re-reading your explanation of “functionally cured” I’m still a bit confuzzled. Could you elaborate on this meaning in a “Definition of ‘functionally cured’ for Dummies” way, for me please?

Many thanks :slight_smile:

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Thank you so much for your response, however, i do have some follow-up questions:

  1. What additional blood tests could provide additional insight to me?
  2. Can I have/develop anti-HBs again?
  3. If my first diagnosis was last month, how am i termed chronic, especially if i am negative for HBsAg. Don’t i need to have another test in 6 months to confirm that?

I have a discussion with my doctor next week and i want to be prepared to ask the right questions, as well as all the test i need to have.

Thank you so much again for all your hard work

No problem. People with a functional cure :

  • are no longer infectious
  • have liver disease that is very unlikely to progress. In fact any liver fibrosis that is there is likely to start reversing.
  • are in a stable condition. Outside of very significant immune suppressants, they are very likely to stay HBsAg-negative.
  1. You could repeat the whole panel. It might be worth considering a fibroscan to determine if there is liver injury.
  2. I don’t see a reason why not. It might be worth suggesting a HBV vaccine to see if you respond with producing antibodies.
  3. I don’t think these tests can show whether you have had a chronic or acute infection.

Hope this helps.
Thomas

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Hello Thomas,
I thought I understood your response, but after re-reading it, i am still uncertain of some issues. It appears my current result put me in the category of might be or unknown.

  1. You state “i may have no HBsAg developed yet”……Does this mean my test was unable to detect a positive HBsAg, and that i might be actually chronically infected?..… am I just waiting for my current negative to turn positive?

  2. I always thought once you develop antibodies against any virus, it will stay with you forever, just in case that particular virus reappears. So what does it mean “anti-HBs antibodies have waned”….In order words, am I below the protective antibody threshold. Does my immune system have a better chance to fight if i become HBsAg positive, because it may already have some anti-HBs antibodies present?

  3. If this will help in your response, my second test on April 15 came back as HBsAg negative and anti-HBs AB negative. However, he did not re-test for the anti-HBc(don’t know why)
    All my other Blood and ALT numbers were normal

  4. He has not put me on any medication yet as he states that with my current results does not warrant it and that monitoring is the key thing to do. I have an upcoming meeting with him soon and i will raise the issue of having a Fibroscan

  5. Lastly, i noticed that some results posted by the community do actually have #’s for their results, whereas, some will only describe it as Positive/Negative/undetected. I don’t know if it makes a difference, but i wish the measurement was standard. Personally, i prefer the numbers as it helps with knowing your trend

I just wish my results was definitive and i don’t find myself in limbo with the different possibilities

Thanks again for all your guidance and explanations

Hi @Yaoman,

I’ll do my best to answer your questions, but of course this is from just the information you’ve provided and other things may be going on.

Sorry, my mistake, I mean HBsAb here. I will go back and edit.

After an infection, antibodies can wane with time, but this doesn’t mean we’re not protected from the virus. You maintain some cells called memory B cells, that don’t actively produce much antibody, but if they are very quickly activated again by exposure to the virus and produce more cells that produce a lot of antibodies.

This is appropriate if you are HBV DNA negative because the medications work on suppressing virus replication. If there is no replication, there’s nothing for the medication to work on.

There are qualitative tests (yes/no answer) and quantitative tests (with numbers) that the doctor can order. Generally the qualitative tests are cheaper than quantitative tests, so they are ordered more often (particular just for screening). Some doctors will order quantitative tests for monitoring trends (as you say), but this is usually reserved for someone with chronic Hep B under active monitoring.

Hope this helps,
Thomas

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