Duration of pegasys for HBeAg negative hepatitis B

According to Roche 2004 trial ( posted in NEJM) 48 week of pegasys resulted in 42% of HBV DNA<20000 copies/ml but it maintained in only 30% after 3 years f/u ( P Marcellin)

A pilot trial ( AM J Gastroenterl 2007;102:2718-2723) pointed out better results of 60 weeks pegasys
( 69% HBV DNA<20000 after 24 weeks off-pegasys periods). It also mentioned greater supress of HBsAg in those who succeed.

It seemed prolonged duration of pegasys is better and duration may be determined by HBs Ag (reduction rate/ reduction amount?) because HBs Ag is a surrogate markers for cccDNA load??

In
http://www.roche-trials.com/patient/trialresults/drugplst_PEGASYS_peginterferon_alfa2a_40KD.html
Roche is trying 72 weeks vs 48 weeks

Do you have any opinion about adequate treatment duration??
The best ( non-invasive) marker for estimating cccDNA amounts in hepatocytes is ??

[alagirl]

I hope you hang around on our boards because truly, most of us have hepc, but we continually get people on here with hepb, and we don't have answers for them.  Just yesterday, a lady posted on a drug called "godex" which I'd never heard of.  It would be wonderful to have this as a more integrated hepatitis format.

Is monotherapy with pegasys the standard treatment right now?  How do they decide the dosage?  Is it a weekly shot?

[stevenNYer]

You profile says you have HepB and are a physician.

I read your other posts.  I'm a little surprised that you seem somewhat dismissive of using antivirals to treat HepB.

The reality of HepB is that there is current no cure.  There are different factors to consider treatment.  I mean if the goal is to for e-seroconversion or to supress HBV DNA, you would not consider anitvirals?  Why?  I'm curious.  I asked 4 doctors on appropriateness for pegasys and they all say, not at this time.

Despite the higher rate a seroconversion to surafce antibody, that rate is still pretty low.  Research indicates that the rate may go up if duration of treatment is lengthened, but for how long?  No one knows at this point and that the problem.  As a patient I don't want to take pegasys indefinately.  If I have a high HBV DNA and can't get it to UND levels on antivirals then I would consider pegasys.  Even if resistance to antiviral occurs, pegasys will still work right?  So why not give antivirals a chance before going to pegasys.  This is my thinking.

Isn't the best marker for estimating cccDNA amounts the level of HBV DNA?.  I'm no doctor but wouldn't it be logical to conclude that if you could reduce HBV DNA to UND levels, there will be less virus to infect the hepatocytes.  And together with CTLs targeting already infected hepatocytes, the cccDNA would go down.  Total elimination of the cccDNA (same as 'cure') is still to be realized.

I would like to hear your thoughts on this.

-Steven

[babamamagogodede]

To Steven:
Most patients take lamivudine but not inject pegasys in our country
As I know, antiviral will cause each infected hepatocyte release less virions per uint of time compared to placebo. It is reasonable that uninfected hepatocytes are safer if viremia is less.
However, I do not think that viremia truly refrects cccDNA load. Under antiviral(s), cccDNA is weaker to make new virions but the cccDNA amount was not largely decreased.

It is almost impossible to wait infected hepatocytes self-cleard because cccDNA replicate as infected hepatocyte replicate.
I think the young is better to take a chance to cure himself the disease. As to the old, it is reasonable to take antiviral(s) lifelong.
Do not forget, all these antivirals are the-like of the-make-of of our genes. They always have the potential to make cells mutation and then to make cancers.

[stevenNYer]

Good post.  By the way nice screen name...the whole family.  I have some understanding of your dialect :)

"I do not think that viremia truly refrects cccDNA load. Under antiviral(s), cccDNA is weaker to make new virions but the cccDNA amount was not largely decreased. ...It is almost impossible to wait infected hepatocytes self-cleard because cccDNA replicate as infected hepatocyte replicate."

Is this a scientific fact or an assumption?  I don't have the expertise to comment on this issue.

But I think we would agree that UND DNA is a good thing.

Lamivudine is still a first-line treatment in you country?  The other later generation antivirals are not available?

I would agreed that Lamivudine is not a good treatment option due to high resistance risk, especially when patient is younger and  / or in immuno-tolerant stage.   I would probably try pegasys in that case as well.  But I think if you are 30-40 and above, antiviral (besides Lamuvidine) is a good treatment option.  

As for risk, it either or.  Risk potential side effects of antiviral or risk documented risk of the virus and high viral load itself.  Like I said, it depends on various factors for each individual.

What specialty is your practice?