Hbs Ag increase after Pegasys

[andrey19]

Hi everyone!

First of all, thank you all for your support and feedback and giving your personal time to comment on my case.

I am now on my 10th week with pegasys 180 mg mono. My viral load HBVDNA baseline was 5000 iu/ml. On the 4th week it became undetectable  (min detecable range 150 iu/ml), which is good but my hbsag quantity is constantly increasing over treatment. My hbsag baseline was 17000 iu/ml, then went to 24 000 iu/ml on 4th weeek and now 26 000 ui/ml on 8th week (All tested by IFA). I also happened to be in Bangkok and tested my hbs by chemiluminescence method on 7th week and my result is 10 000 iu/ml, I also check hbvdna by CobasTaqMan and it was 32 ui/ml (min detectable range 20 iu/ml). Why is it that much difference between methods in Hbs?  Which one is more reliable?
I am so depressed with these results!I certainly did not expect Hbs to go down to zero but it least not to increase! People what do you think? Does it make any sence to continue with pegasys?

[stef2011]

alinia, simvstatin, vit d3 and maybe vit b12 too but the effect on intf boosting is mild and just confirmed on hcv trials

a member tried simvastain+intf and cleared very fast by about 16weeks another member tried intf+alinia+d3 and had few hbsag decrease

[stef2011]

yes that s the best way and it works because tdf reactivates dentritic cells after a couple of years which are necessary for intf to work

[nihi120]

Thanks..does any medicine or other method to boost IFN. Any chance to be HbeAg become negative while this much higher value of HbsAg?

[calebz]

Yes,that is the current "theory". Study to see if it is better to go with TDF+IFN combo is currently running.. ETA is 2014 december.

[Rome70]

Would it be better to decrease virus replication by tdf first and then when dna is under add intf toactivate immune respons to clear hbsag?

[stef2011]

intf is failing to activate an immune response but i ll wait and see because tdf may help to reactivate intf response later on, also this hbsag up and down can happen in slow respnders

if intf fails to decrease hbsag even at 48 weeks it is best to stop intf and keep tdf mono, intf can be tried again 1-2 years later and then it is easier to work

[djxpress]

the amount that your HBsAg is going up is really insignificant.  If it goes up by a log i.e. from 30,000 to 300,000 - then that is significant.  Theoretically, as your HBV DNA goes down, your HBsAg should drop slightly as well.  

Studies have shown a strong correlation between HBV DNA quant and qHBsAg at higher levels, but a weaker correlation at lower levels, i.e. 1,000 IU and less.

[Rome70]

I also read somewhere that quantity of cccDNA correlates with q-hbsAg.

[nihi120]

Hi All,

I am also undergoing treatment of TDF+PEG. I have just received my week 25 result and very confuse, Here is the complete history to the latest of my result:

Baseline result (mid of May)
Hbs Ag (Quant) : 37903 IU/ml
Hbs Ag : Reactive
Hbe Ag : Reactive
ANTI-Hbs:Non-Reactive
HBV DNA : >1.10x10^8 IU/ml
AST : 42
ALT : 65
June result (week 4)
Hbs Ag (Quant) : 22583.7 (going down)
Hbs Ag : Reactive
Hbe Ag : Reactive
ANTI-Hbs :Non-Reactive
HBV DNA : 320735 (going down)
August result (week 12)
Hbs Ag (Quant) : 36915.98 (going up)
Hbs Ag : Reactive
Hbe Ag : Reactive
ANTI-Hbs :Non-Reactive
HBV DNA : 13825 (going down)

Nov result (week 25)
Hbs Ag (Quant) : 37468.4 (going up)
Hbs Ag : Reactive
Hbe Ag : Reactive
ANTI-Hbs :Non-Reactive
HBV DNA : 152 (going down)
AST : 43
ALT : 55

Should I add any other medicine? My Doctor is saying treatment is going good don't see qHbsAg. I am not facing any side effect. What is your opinion?

[stef2011]

low hbsag reflects immune control and low cccdna it doesn t matter which treatment or off treatment
also hbsag quantity does not correlate with hbvdna or alt

[stef2011]

it can be both, lets see how it goes at 24 weeks and update then

[andrey19]

Hi Stef! I made 3 test with same lab and qHbs is increasing each month. What do you think is it? Dillution problem? or Interferon is not working on my Hbs?

[StephenCastlecrag]

Let me take one step back. When I say scientists now believe that low hbvdna + low qHBsAg together indicate a truly inactive phase - this applies to HBeAg negative patients who are not on medication. They usually have very low hbvdna and normal ALT, and yet some do go on to develop severe fibrosis. This is partly, in my opinion,  because hbvdna and ALT are not being monitored constantly and so some of these patients actually have fluctuations in their hbvdna and ALT. So how do you distinguish between those who are truly inactive and those who appear to be inactive? Here, qHBsAg serves as a good indicator.
For patients on potent antivirals, hbvdna should be kept at very low level, so ALT is normal, and so qHBsAg is less useful as an indicator.

The levels of qHBsAg vary between different phases: highest during the immune tolerant phase and lowest during the inactive phase. Scientists believe the amount of serum HBsAg is a reflection of the amount of "transcriptionally active" cccDNA in the liver. HBsAg is produced in much more quantity than is needed to coat the new virions. So you can have zero hbvdna and yet a high level of qHBsAg in your blood.

So the goal of treatment is to avoid damage to the liver (indicated by normal ALT) by reducing hbvdna to as low as possible (because immune system is activated by virions(hbvdna) in the liver.

So far I have not read any scientific literature that directly links qHBsAg and risk of HCC. Cirrhosis is the biggest risk factor for HCC, and cirrhosis is accumulation of scarring caused by replacement of liver cells damaged by the immune system.

[stef2011]

you need to check hbsag by same lab and same machine otherwise you get different numbers, there is also a possible error of about 1000iu/ml if the sample is diluited manually
new kits dont need manual diluition so there is no error for this

[andrey19]

thanks for your message. I will surely go further with pegasys and I do not experiencing any sides except of my first shot. As for qHbs is reported everywhere that less than 1000 iu/ml is low. What is the medium range? Is it like up to 10 000 or maybe 20 000 iu/ml?

Please correct me if I am wrong. Since hep b is not curable now. The only way we can manage virus is to make HBV DNA undertectable or at least as low as possible. Undetectable DNA means currently no (or little) damage to liver thus greatly reduces risk of HCC and cirrosis NO MATTER HOW HIGH YOU QHBS IS?

[andrey19]

Oh i see, The girl over the phone confirmed me that in order to make qHbs they have to dilute serum by hands and then see the quantity. So the test that I made in Bangkok hospital is performed by automatic dilution, seems more accurate. I am amaized that error gap is that big.

[StephenCastlecrag]

I am not a doctor. I agree that the rise in qHbsAg is really unusual, especially when your hbvdna is lowered by your Peginterferon treatment. It is believed that Interferon has a weak antiviral(reduce hbvdna) effect and immune modulation effects one of which is to reduce the transcription of HBsAg. So this is really a puzzle.

As far as association between qHBsAg and liver cancer, I think you misunderstood. It was believed that a low hbvdna reduces the risk of HCC, but scientists have now refined this further to say that a low qHBsAg + low hbdna together indicate a true "inactive" phase and therefore lower HCC risks. There is no research that showed qHBsAg is a sole indicator of risk for HCC.

As for continuing treatment, personally, I believe you should continue to week24 if you are not suffering any significant side effects. HBV is tricky and rules are just general. Ultimately it is still whether your hbdna is lowered and your ALT is normalized.

Just my opinion.

[Rome70]

Hi Andrey!

10th week is too early to tell about the treatmemt progress. Especially when your hbsag test are kind of unreliable.

As for the testing methods, the problem is that the machine testing range is 0.5 - 255 and to test anithing above that they have to do manual dilution and this is when the error comes in. It is too dependant on the operator. The problem is that the result is not in IU but in the units they only know, and also it is inconsistent even if they test the same blood twice it may well be 30% difference.
There are machins with automatic dilution, that are accurate but i have not found any in Moscow yet.
So make sure the result is in IU ask them to provide it in written, because the girls  on the phone normally do not even understand the question.

[andrey19]

Thanks for your message. I am e-antigen negative. It seems to work on DNA but not on Hbs. I know I have to stop worring but it seems today is the day of panic for me. There are so many reports now saying that Hbs over 1000 iu/ml increasing risk of liver cancer even low or und DNA and my Hbs is increasing month by month even on pegasys.

[Mrt79]

Hi Andrey,
You need to provide more information.
What was your HB status? i.e. e-antigen positive or negative?
It sounds like pegasys is actually working for you and you have only been on Pegasys for little less than 3 months.
Give yourself a chance and worry less.
Good luck with you treatment..