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?)
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:
You have had a chronic infection, cleared the infection, and are functionally cured. You may indeed have no HBsAb developed yet.
You have been exposed earlier in life, had an acute infection, cleared the virus, and your HBsAb levels have waned.
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.
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?
Thank you so much for your response, however, i do have some follow-up questions:
What additional blood tests could provide additional insight to me?
Can I have/develop anti-HBs again?
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.
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.
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?
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?
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
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
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
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.
I haven’t written for a long time, but I read you all with great interest.
Regarding this topic, I am very interested, since for a few years now I have been observing that my viral load has gradually decreased.
In September 2023 my results were as follows:
HepB Antigen Index: 181.13
HBsAB: 3 UI/mL
HBV Viral Load: 249 UI/mL
and in September 2024 the following:
HepB Antigen Index: 9.49
HBsAB: 1 UI/mL
HBV Viral Load: 67 UI/mL
The doctor tells me that if I continue to evolve like this, next year it is very possible that I will be “functionally cured”.
Although I am worried that even though the viral load decreases, the AB do not increase.
Is it possible that the AB rise to > 10 UI/mL?
My question is, if with the higher viral load before than now I have not been able to generate AB, with a decreasing viral load, maybe there is not enough virus to stimulate the inmune system and create AB… or it is expected that the AB will increase over time?
Thank you all for your work and contributions to the community.
HBsAg antibody production in a therapeutic setting does not necessarily have the same meaning as when observed during prophylactic vaccination.
In the vaccine setting, anti-HBs production > 10 mIU/mL is a reliable marker to prevent the development of chronic HBV infection.
However, with functional cure, many persons do not have detectable anti-HBs or have anti-HBs < 10 mIU/mL. For this reason, the production of anti-HBs is NOT included in the definition of functional cure. We know from several clinical studies with NAPs and therapeutic vaccines that the production of anti-HBs does not guarantee functional cure.
You should focus on the clearance of HBsAg while you are on NUC therapy (this appears to be happening based on the results you provided above). If you persist with HBsAg clearance continuously for 6 months or more while on therapy, your doctor may decide to halt your NUC therapy. At least for the first 6 months, you should be seen more frequently. If you maintain HBsAg loss in the absence of therapy for at least 6 months, your immune control is restored but just not detectable by the anti-HBs test.
Thank you @availlant for your reply, but I am not currently, nor have I ever been, on treatment.
I have always been a carrier with a low viral load and under medical supervision every 6 months, but for approximately 2 years I have observed that the viral load has decreased to the values I have indicated…
Is there any difference between my current situation being due to it being natural and spontaneous, or if it was through treatment?
In order to understand why this is possible, it is important to recognize that your chronic HBV infection is not genetically homogenous. Instead, it comprises thousands of genetic variants because of the relatively high error rate in replicating the viral genome relative to other viruses. Many of these variants produce HBsAg which is immune escape towards the patients existing immune responses.
This, while you are producing some HBsAg antibodies against forms of HBsAg while are mostly non-existant in your blood, there are other HBsAg variants in your blood which are not recognized by the anti-HBs you are producing. This kind of immune response (even when > 10 mIU/mL) unfortunately does not provide any meaningful control of your HBV infection.
If you are taking NUC therapy, you should not stop this therapy unless HBsAg becomes undetectable, regardless of the presence of anti-HBs or not.
For the community at large, it is also important to understand that the situation with the prophylactic production of anti-HBs prior via vaccination prior to infection is very different. Here the production of wild type anti-HBs effectively protects against the development of chronic HBV infection.
I trust you are well. May l ask if you received vaccination after your results? I am in a similar situation only that my hepatitis core test (total) is inconclusive. I would like to hear what your doctor advised for you
