HBS Ag increase and loss of HBE antibodies on tenofovir

Dear Community,
I am lost for words and hope there is someone who could help me make head or tails of my recent results.

I have been on Tenofovir for 1,5 years. When I started I was HBE AG negative (and still am) and anti-HBE positive (tested twice and both were positive).

This month I tested negative for anti hbe. On top of that HBS AG has increased by 8000 from April 2022 till January 2023 (from 19500 UI/ml to 27800 UI/ml).
HBV DNA is undetectable.

How is this possible? If I have such low virus levels, how come HBS AG is increasing? It should be the opposite, shouldn’t it?
Also why would I lose anti-Hbe?

I would appreciate any comment. Thank you!

Dear @Natti ,
My advice is to keep calm and be positive.
I had about the same experience with HBs Ag, increased by 10x in about 3 months after being in decline for about a year. I was shocked and surprised seeing big numbers and my doctors could not give me an explanation. I decided to repeat the test at a different lab and came back a lower quantity, which was expected. I presume that the results depends on the labs, the person who does the blood work (how much reactive uses, the hand, etc). I am sure that the experts from this community can help you better than me.
My advice for is to repeat the tests at a different lab if this is possible for you and don’t panic :relaxed:
Hope you will find an answer!
Keep us posted.


Thank you, Ecky. Much appreciated. I will try to retest for that. Any experience with the loss of antibody HBE?

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Dear @Natti ,

First, quantitative HBsAg testing in a properly accredited lab will use approved tests (typically Abbott Architect or Roche Cobas platforms) which are standardized to an international HBsAg standard provided by the WHO. Changes in HBsAg of the magnitude that you are observing should not be coming from assay variability.

It is important to note that > 99.99% of HBsAg is produced independently from viral replication as subviral particles and is not directly impacted by any NUCs (including TDF).

There is no good, high resolution data published for HBsAg response during TDF so your case is interesting. It does not mean that the viral infection is returning. It more likely reflects mild changes in the secretion of subviral particles. I do not see any reason for concern.

Best regards,


Thank you Andrew, @availlant. Much appreciated.
I am just concerned because there are reports of HBS AG decrease however negligent it may be. I have never seen any report of increase - I am of course no expert.

Any thought on the loss of HBE antibody? This seems more concerning to me… How come I no longer have it and can this be a sign of HBE AG becoming positive again?

Hi @Natti

The problem with looking at published overall HBsAg decrease with NUCs, which is typically very mild, is that these studies do not report individual HBsAg responses overtime. It is possible that your observation is not so abnormal, just “hidden” in the way clinical data is reported in the literature. There are large spread of possible HBsAg responses to TDF varying from no response at all (I tihnk this is your case) to 1 log decline from baseline (the most common) to rapid HBsAg loss (very rare and typically restricted to very recently acquired genotype A HBV infection).

The goal of NUC therapy is not functional cure but control of viremia and preventing progression of liver disease. These appear to be well under control in your case.

The appearance and disappearance of HBeAg antibodies can be driven by many different issues: for example you may have some mild change in your immune functioning (this can be affected by stress levels). There could be a reduction of anti-HBe because of a protracted absence of HBeAg in the blood. It could be that your next test will show the return of anti-HBe antibodies. None of these impact issues impact the ability of TDF to control your viral infection and prevent the progression of liver disease. Some patients on TDF never develop HBeAg loss and continue to have their HBV infection and liver disease well controlled.

Hope this helps…


Thank you Andrew @availlant.
This is great consolation.
The problem is I have very little understanding of the virus and cling onto any information I can find and then interpret it my way.
I am very grateful for this community!


Hi @Natti ,

This is one of the very important reasons why Thomas created created this forum and why we are here. To sort out confusion for patients like you!