Rebound of HBsAg

Hi everyone!
I’ve been here for a while and enjoying the topics, discussions and experiences shared in this community. I am grateful for finding so much information about HBV as I am a CHBV female who wants to know more about treatment, invention and development of a new cure for HBV.
In spring, 2020 I was diagnosed second time with CHBV and took it in serious, because the first time being diagnosed (10 years before the second diagnosis) I was told not worry about it and that I will have a long and normal life and completely didn’t care about HBV. I have to mention that my mother died 9 years ago because of the complications of HBV+HDV and HCV.
My twin sister had HBV too (diagnosed with me in 2010)but in 2020, her HBsAg was negative and HBsAb positive (>1000).
Since 2020, I have been participating in several trials and a year ago I’ve started taking TDF. My DNA has been undetectable 3 months after starting TDF(the time when I repeated DNA test).
My HBsAg levels were:
September 2020: 4634,00 (different laboratory)
05 May 2021: 2173,47 IU/ml (my preferred lab)
May 2021: 1401,00 (different lab)
Anti-HBs 2 IU/L

June 2021: 980,00 IU/ml (different lab)
10 September 2021: 9116,00 IU/ml (different laboratory, I was shocked seeing this result, then I decided to repeat it at a laboratory I usually do it)
28 September 2021: 2050,00 IU/ml (my preferred laboratory before starting taking TDF)

April 2022: 1650,33 IU/ml (my preferred laboratory after 6 months of TDF)

October 2022: 67,9 IU/ml (my preferred lab) after one year of TDF and plus about 22 weeks on AB-729.

My question is, if HBsAg level has dropped so much since last time (6 months apart) might rebound after being off medications (TDF, AB-729 and Pegasys)?
Or, HBsAg is not able to rebound as HBV DNA does?
I am participating in AB-729 trial and want to know what might happen/to expect after stopping taking the medications.
What are the expert opinions?
@ThomasTu
@ScienceExperts
@availlant

Thank you!
Every blessing!
Ecky

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Dear Ecky,

Unfortunately we know from several phase II trials with numerous RNAi (including previous trials with AB-729) that most if not all patients HBsAg rebound following treatment, even following 48 weeks of exposure.

This is also the case during pegIFN therapy when HBsAg is not reduced to < 1 IU/mL.

Best regards,

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Hi Ecky!

Great questions and lots of those questions I too am asking myself, being in the same trial, with my first dosing a month ago (go for first bloodwork tomorrow). I am not a scientist, but what I do know is HBV is very unique to each of us. We all hope to be like your sister and this is what that trial is trying to do, jumpstart the immune system with what I like to think of it as a one (NUC we already take) two (the experimental drug) and three punch (interferon) since they do know to functionally cure HBV it’s going to take a multistep approach. Possibly some of us will be functionally cured soon or later after trial (since interferon does work continue to work after it is stopped for some that respond) or possibly some of us may be able to jumpstart our tired immune system and have our body control HBV without the NUC, but still stay HbsAg positive? Or maybe it this study will fail to produce any meaningful benefit long term at all? This is why we are in the study, to help others and possibly help ourselves, which is exciting! The good news is that now that HCV is cured the trials are turning to cure HBV, something I have not seen since the updated NUC’s came into the market, which we do know do not functionally cure the majority of us. I’m 49, so feel I don’t have much time to get a real benefit of a cure, but I also know that most of us that take care of ourselves and do the necessary precautions needed do not die from HBV. I hope this helps from another patient point of view and I hope for you and all of us in this study (and others going) the 1,2,3 approach will restore our immune system to do what it’s supposed to do. Best wishes!

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More thoughts…your sister is also very unique with chronic HBV to not only have lost HbsAg but also to have mounted an amazing antibody to fight HBV naturally if needed in the future. Did she naturally accomplish the loss? This trial is at best, I believe, trying to functionally cure, meaning hopeful loss of HbsAg but very well may not produce antibodies, which means that later HbsAg could turn positive again in the future. I am really nervous when it comes to going of Vemlidy. I do know that some that go off their NUC is a good thing and needed for the body to fight/control HBV and further HbsAg loss, but it also can turn out very badly if not strictly monitored. But, I do feel the benefit outweighs the risk at this point but feel any of us that do clinical trials are nervous, but this is what is needed to test and ultimately get to a point of a cure I also know.

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My sister’s case, I’d say is a miracle. She’s naturally accomplished the loss, without even realising her body was fighting a chronic hepatitis. She like myself was told not to worry about the infection but, praise God she’s been healed. Some doctors couldn’t believe so she had to repeat the tests couple times and at different labs :blush:

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I had my fourth injection yesterday :blush: and in 4 weeks I’m starting interferon. Hopefully with HBsAg <100 I will achieve functional cure and of course I’d like to have some antibodies but only God knows what has in store for me.
It will be a great joy for me knowing that @3kids4me has achieved functional cure too.
I am grateful for the chance of being part in medication development process!

Best wishes :hugs:

Only God does know for sure and I pray we will be on the forefront of being functionally cured! What a blessing for your sister and hope you follow in her footsteps very soon!

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