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Wife saw spontaneous HBeAg seroconversion in <1 month, HBsAg lowers
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Wife saw spontaneous HBeAg seroconversion in &lt;1 month, HBsAg lowers

Guys, I hope to get some ideas from you on my wife's situation. She's not on any treatment now.

As I mentioned in an earlier post my wife was diagnosed to have activated her Hepatitis B after she gave birth to our daughter in Jan 2014. The new news is that in latest checkup we found out that she has quickly seroconverted HBeAg within one month. ALT & AST are both very close to normal ranges now but still slightly above. HBV DNA undetectable (<1,000 copies/mL).

Another thing is that her HBsAg dropped from 1128 IU/mL one month ago to 505 IU/mL. I kinda feel this is all positive movements, but not knowledgeable enough to tell:

1. Why did the HBeAg seroconversion happen so quickly in 30 days? Any chance of a bounce-back?
2. ALT/AST is still not normal yet although DNA is already und, but shall I consider this as a good sign since this might indicate a chance of a HBsAg further drop?
3. What options do I have now? to wait for another month or start interferons?
4. Am I crazy to imagine that she would clear HBsAg all by herself and develop HBsAb without any drugs/interferons? What all happened was just a bit dramatic and beyond expectation to me.

Thank you everyone for your opinions!

=====Her Data=====
On Jan 6, 2014:

HBsAg: 1128 IU/ml
HBsAb: <6.4 mIU/ml
HBeAg: 224 CI
HBeAb: <30 INH%
HBcAb: 99.9 INH%
ALT:    116 @ Jan 4; 195 @ Jan 6; 173 @ Jan 8
AST:    130 @ Jan 4; 130 @ Jan 6;  98 @ Jan 8
HBV DNA: 5.4x10^5 copies/ml

On Feb 5, 2014:

HBsAg: 505 IU/ml
HBsAb: <6.4 mIU/ml
HBeAg: <1.0 CI
HBeAb: <76.8 INH%
HBcAb: 99.2 INH%
ALT:    51 IU/L
AST:    38 IU/L
HBV DNA: <1,000 copies/ml

She's Asian, 27 years old, genotype unknown
We believe she got infected before 10 years old, but not when she's born.

My post when we first discovered her activation
http://www.medhelp.org/posts/Hepatitis-B/Need-advice-before-seeing-doctor-again/show/2078206#post_9844997
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Avatar_m_tn
I am glad that things are moving in the right direction for your wife. I am not a doctor but will try and give you my opinions.
1 Obviously, your wife has seroconvverted her e- antigen naturally. During pregnancy, the immune system is naturally suppressed because of the fetus. So there is a rebounce in the immune system after birth. I think you will find what happened to your wife is not rare. The e-seroconversion is always a bit of a mystery. It heralds the end of immune clearance and transition to the immune control (inactive) phase. There is a chance of going back to e-antigen positive, but unlikely in my opinion because she did it naturally.
2. The qHBSAg may drop further, but unlikely because her ALT is really not that elevated, but that is just a guess.
3. I have no idea whether she should start IFN to see if it will help her to clear the virus. You may like to ask her doctor.
4. In the natural history of HBV, your wife may stay in this phase for a very long time with some chances of eventually losing her HBsAg altogether. However, in a percentage of patients, they will transition to the immune escape (re-active) phase due to mutation of the virus.  If your wife' qHBSAg drops below 100 iu/ml, this would indicate she is in a truely inactive state. So an annual check-up is important.

Finally, did you find out anything about arc520 clinical trial?
28 Comments Post a Comment
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Avatar_m_tn
Sorry correct one data:

HBeAb on Feb 5 was 76.8 INH%, not "<76.8 INH%"
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Avatar_m_tn
I am glad that things are moving in the right direction for your wife. I am not a doctor but will try and give you my opinions.
1 Obviously, your wife has seroconvverted her e- antigen naturally. During pregnancy, the immune system is naturally suppressed because of the fetus. So there is a rebounce in the immune system after birth. I think you will find what happened to your wife is not rare. The e-seroconversion is always a bit of a mystery. It heralds the end of immune clearance and transition to the immune control (inactive) phase. There is a chance of going back to e-antigen positive, but unlikely in my opinion because she did it naturally.
2. The qHBSAg may drop further, but unlikely because her ALT is really not that elevated, but that is just a guess.
3. I have no idea whether she should start IFN to see if it will help her to clear the virus. You may like to ask her doctor.
4. In the natural history of HBV, your wife may stay in this phase for a very long time with some chances of eventually losing her HBsAg altogether. However, in a percentage of patients, they will transition to the immune escape (re-active) phase due to mutation of the virus.  If your wife' qHBSAg drops below 100 iu/ml, this would indicate she is in a truely inactive state. So an annual check-up is important.

Finally, did you find out anything about arc520 clinical trial?
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Avatar_m_tn
Stephen,

Thanks a lot for your opinions. Maybe to stay at status-quo would be the best scenario for her at this moment.

As of ARC 520, we are seeing the doctor on Feb 14th (the coming Friday), The hospital is one of the two hospitals where the trials will be taking place.

The doctor we are seeing is not the one conducting the study, but he's the best they have, he's a professor. I'll try to ask him. It looks like the enrollment has finished, so maybe ask him about efficacy if the test has started. It's just a single-shot trial so it should be fairly quick.  
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Avatar_m_tn
To add one point:

For the past 10 days my wife has again started to feel the symptoms, mainly nausea, is this normal given her only slightly alleviated ALT/AST? how should I interpret this phenomenon?
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Avatar_m_tn
Thanks for the update. We know the trials will be conducted by Professor Yuen and Professor Chan at their respective hospitals. Anyway, according to Arrow Head, they are still waiting for the go ahead from Department of Health.

As for her nausea, you are sure she is not having another baby? It is not a known symptom of Chronic HepB.
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Avatar_m_tn
Then at least can ask them whether they've received the go ahead.

As of nausea, I always thought it was due to HepB, she's not having another baby for sure, and at China health forums Nausea is a very common symptom I will say..
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Avatar_m_tn
In that case, best to consult your doctor.

I am also a frequent visitor to hbvhbv.info.
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Avatar_m_tn
After my wife delivered our first child her ALT shot up after 3 months. At first we were very frightened but then we learned her HBVDNA declined which  had increased during pregnancy.

Stephen is right, the immune system is suppressed during pregnancy and is heightened after.

I'm curious what effect it has on the Surface Antigen. If it declines I'm wondering if Interferon would help?
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Avatar_m_tn

pegintf would definitely amplify her immune response clearing hbsag very fast but the best thing is to follow hbsag and use pegintf if it stops declining.her nausea is probably due to immune activation and her own interferon
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Avatar_m_tn
Thanks imran for sharing your experience. I wonder whether your experience with you wife's first pregnancy made you reluctant about having a second kid? Sounds like immune system is deemed to be suppressed during pregnancy and risk reactivation of HBV during 2nd pregnancy? any way to prevent this?
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Avatar_m_tn
we have observations of this in posts about gcmaf.

the immune system is suppressed to protect the fetus from attack and natural abortion, immune suppresion is made by nagalase which inactivates macrophages which are the main/first sensors for invaders by our immune system

also hbv, hcv, flu virus, cancer cells, bacteria and other viruses make nagalase to suppress our immune system it.our own nagalase is little different and in healthy person is less than 0.6

after delivery our own prodcution of nagalase go down and macrophages reactivate

without immune suppression there is abortion, no way to deliver baby safely without it
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Avatar_m_tn
Thanks stef, I remember that post about gcmaf, I'll go back read again.

If say a woman has already HBsAg seroconverted, and developed HBsAb, does the immune suppression mechanism during pregnancy still post the same risk? thanks!

One question since you mentioned cancer cells - since cancer cells make nagalase to suppress immune system, could this mechanism serve as a universal treatment target for generally all cancers? Is there any research going on that targets nagalase? sorry my medical background is almost close to zero!
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Avatar_m_tn
If say a woman has already HBsAg seroconverted, and developed HBsAb, does the immune suppression mechanism during pregnancy still post the same risk?

i guess not i ve never seen studies on this, that isn t so severe immune suppression and nagalase levels are very high around fetus for sure and not the whole body.
anyway it is easy to monitor by hbsab levels and if they fall tenofovir can be used

One question since you mentioned cancer cells - since cancer cells make nagalase to suppress immune system, could this mechanism serve as a universal treatment target for generally all cancers? Is there any research going on that targets nagalase? sorry my medical background is almost close to zero!

yes researchers in a swiss hospital using gcmaf.eu are publishing people with 3 months left to live with tumors reduction of 25% per week (when not multiple tumors), they just started in december so too eraly for the follow up publication.if reduction is less the patient dont pay the hospital, they are getting this because they inject gcmaf close to the tumors or on the veins that supply the tumors by guided high sensibility ultrasound and of course nutrition intervensions

they had front page of oncology immunology on august 2013 and i guess at end of 2014 we will have the follow-up publication and know how many of these dying persons were saved

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Avatar_m_tn
also the japan team of scientists from saisei clinic has published some reports, but i dont follow that too much
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Avatar_m_tn
Thanks Stef. I guess my hope is that my wife's HBsAg was low at 1100 when upon first check and quickly dropped to 500 one month later, so I am hoping that she could spontaneously clear HBsAg in months (tell me if this is crazy thoughts).

Thanks thanks for the cancer briefing. It is great to know. Personally I know very little about this field (even HBV, which I know little until not long ago!)

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Avatar_m_tn
just follow hbsag monthly so you are on time to catch if the decline stops, i guess genotype is asian, so B or C.just another though on genotypes

in case of genotype C maybe peg add on canbe justify with the high liver cancer risk and the less predictive role of low hbsag, while geno B is safe enough to wait for spontaneous clearance
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Avatar_m_tn
We got an update on data. We havn't got the whole thing but looks like:

1. HBVDNA bounced back to 6,576 copies/ml, from previous <1,000 copies/ml
2. HBeAg re-appeared reactive. She had seroconverted HBeAg before during 2014-Jan~2014-Feb short period of time.

Doctor said in the phone that the DNA suppression and e-seroconversion we saw before were just a temprary immune responce after She delivered the baby. When that stage ends DNA and HBeAg will bounce back like what we are seeing now. He suggested us to start TDF. Her ALT/AST is 37/30, while the lab's high-end reference is 36/30.

We have not received quantitative HBsAg yet, but the doctor kept emphasizing that it is "not very useful".

We didn't immediately agree on taking the meds, but suggested repeating a blood test after one month. Because my thinking is, since she's getting to the end of the "immune flare" stage, will she set back to a immune tolerence stage again?

I will post full result after we got all reports. Thank you guys for your opinions!
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Avatar_m_tn
I would wait to see if the viral load comes back down again and the e-antigen turns negative again.  There is no rush to start medication, in my opinion.
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Avatar_m_tn
We have not received quantitative HBsAg yet, but the doctor kept emphasizing that it is "not very useful".

on the contrary this is the most important test because if this increases to higher than 1000iu/ml you lose all possibilities to clear by peg.i d go for peg or tdf and then peg as soon as possible before the chance is lost
tenofovir will make hbvdna undetectable but hbsag may continue to rise despite tdf

is genotype B or C?

of corse the goal here is hbv cure, if we mean to manage the infection only there is no rush at all and the rush of the doctor to start antivirals is not justified becuase there wont be liver damage so fast and fibroscan can track  when this will happen and then tdf is needed
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Avatar_m_tn
so peg mono or tdf until hbvdna undetectable and then peg add on
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Avatar_m_tn
Thank you Stephen and Stef,

My best hope is of course that we would see a decrease of HBsAg (result not out yet), then I can push a case for Peg (with or without TDF), though looks like I really need to persuade the doctor.

Another hope I have is that she will probably go back to immune tolerance stage. She has went through immune clearance => immune control => weak immune clearance with ALT/AST = 37/30. Maybe it's possible for her to set back to just a carrier again.

I will post her HBsAg once we got it.

Thank you guys again for following up, you guys had given me a lot of courage and I'll try to contribute to the community in my ways.
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Avatar_m_tn
Stef & Stephen,

We received the HBsAg, 329 IU/ml. declined from 1100 in Jan to 500 in early Feb and now 329 IU/ml. ALT/AST=37/30, HBV DNA=6.577 copies/ml.

The doctor made some points:

1. He agreed to have another blood test next month, before making a decision on therapy.

2. After I (again) suggested interferon because HBsAg declined, he again said HBsAg is not that useful, firstly because her viral load came back to 6,577 copies/ml,

secondly because pegsys even if successful, there is still risk of HCC or cirrhosis. However I do remember him saying in previous meeting that "If you seroconvert HBsAg before 50 then you dont have HCC risk". He's a researcher so that must be paper-supported. Not sure whether he's saying something different now because DNA is no longer und.

BTW, his attitude towards interferon is not alone in HK, the other doctor we saw also said "Pegsys is rarely recommended due to sides and low successful rate, only for those who's young and willing to put it all-in for once". I think it comes from their experience.

You guys have all given me your valuable opinions above, so I guess not much has changed here. But if I was really missing some treatment window here by waiting for another 1-3 months doing nothing, please do tell me...

I think if we do nothing here what will likely to happen is HBsAg stops declining (or even go up), viral load go up, AST/ALT back to normal (already almost normal). Can I consider that as an immune tolerance stage and thus no therapy would be needed?

Thank you guys for your opinions!

Below is a link to her complete record, easier to read.

https://docs.google.com/spreadsheet/ccc?key=0Aof1yq4cmKBmdGxNSGFtZVQ2eFNTS19BTmg4Ri0wemc&usp=sharing#gid=0

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Avatar_m_tn
I think you are missing the reasoning of our rationale to consider IFN when qHBSAg is low. Most research indicates IFN can lower qHBSAg. So when qHBSAg is reduced to a very low level, we then assume our immune system will kick in to achieve a curve. This has not been universally accepted by the doctors, and rightly so, because there are insufficient clinical data to support this conjecture. So our suggestion is always considered to be an experiment, one we believe has a high chance of success.

As for HCC, it's risk is reduced, but never eliminated, by a cure or maintaining hbvdna at an undetectable level.

I don't know about the bias against IFN treatment by HK doctors, I doubt it is from experience.
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Avatar_m_tn
check if there is any conflict of interest or if public healthcare pays for peg, i dont see any reason against trying pegintf afterall you have 24 weeks to try and see, use of an antiviral won t make any difference or any cure now

you can also see the members here, all those with less than 500iu/ml cleared here

so i d prepear your wife immune system for peg by vitamin d levels at optimum range and then i d try 24 weeks.antivirals can be taken any time in the future and wont clear hbsag
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Avatar_m_tn
Can I consider that as an immune tolerance stage and thus no therapy would be needed?

no she is not immune tollerant, hbsag is too low and hbvdna is still low, 6000iu/ml is a very low hbvdna
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Avatar_m_tn
Thanks Stephen & Stef,

check if there is any conflict of interest or if public healthcare pays for peg, i dont see any reason against trying pegintf afterall you have 24 weeks to try and see,

We are seeing the private side of the hospital, it's like the same doctor but he goes to both private and public side of the hospital. So we are paying for everything. Indeed strange why doctors dont like it.

How do you see that her DNA goes up from und but HBsAg goes down from 500 to 329? Looks strange to me. Could it be that HBsAg had actually been lower, but bounced back together with DNA?
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Avatar_m_tn
Personally, the reason I suggest that you wait for the results of a further test is that hbvdna can go up transiently. So, if there is no urgency, it is often better to rely on the trend rather than just a single reading.
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Avatar_m_tn
Stephen,

Got it. I do hope the next result in March would show some improvements.

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