Hep B

[cally44]

Hi

I was wondering if someone could give me a good understanding of my hep b case. I was diagnosed last year of having chronic HBV. I am sure I got it from birth through my mother who has already cleared the virus. I am Asian in my early 30's and I don't know my genotype. My ALT And AST were rock normal and my dna was in the 800's iu/ml pcr. In Sept of last year I did another series of tests and everything was normal except that my alt and ast were a little raised to the 50's and 60's but my dna was undetectable. I also did an ultrasound and everything looked normal. MY AFP was also within range of the lab.

My GI specialist told me to check my blood and do another ultrasound after a year. I thought it was 6 months that one should do these tests.

Now could this be a sign of clearing the virus since my dna was undetectable? Can your dna be undetectable one day and then jump up to a crazy number the next?

Also, is it safe to say I am not a precore mutant? I am e antigen negative and e antibody positive.

Thanks for the help

p.s. Hepbresearcher, I am asian yes and in my 30's with asian background.  How can I do the genotype test to make sure I am not a precore mutant?

[cally44]

Thanks HepBresearcher,

So can I just ask my GI specialist for a genotype test and if I am genotype A, I can be assured that I am not precore mutant right?  So will I just be a carrier for the rest of my life without going on any sort of antiviral?

Also, my other question is that my mom who I think I got this disease from had it many years ago while living in the far east.  Her titre showed 50 (antibody) and no antigen is present so she has cleared it.  Now, what I want to know which I haven't received an answer is was she a chronic carrier who seroconverted given the fact that her titre is 50 and not higher or do you think she had acute HBV and then was the 95% that cleared it within 6 months?

My other question is that my doctor said I only need to test myself once a year (ultrasound, AFP, and blood tests).  Do you think I should ask him to do it in 6 months time or wait for a year?  Right now my AFP is 5.7, ultrasound showed normal, and everything else was within normal lab range.

Thanks, you should join the Hep B list serve...have you heard of it?

Cally

[jboyhk]

This site shows the 'definition' of the clinical profile of a precore mutant. It seems ALT elevation is a key component.

http://www.medscape.com/viewarticle/459763_2

In such patients, the diagnosis of HBeAg-negative CHB can be made when the following criteria are fulfilled (Table):

Increased serum ALT level (ie, ALT levels > 2 x upper limit of normal [ULN] on 1 occasion, or ALT > 1.5 x ULN on at least 2 monthly determinations), as a biochemical marker of ongoing hepatocellular damage;

Detectable serum HBV DNA levels, to establish active HBV replication and, presumably, HBV-induced hepatocellular damage;

Exclusion of other concomitant or superimposed causes of liver disease; and

Moderate-to-severe necroinflammation on liver histology, compatible with CHB.[32,33]

[cally44]

Hi

So Hepbresearcher, I am a little scared and nervous after reading your message.  Can I have a pre-core mutant in me?  My first DNA showed 850iu/ml and now it is undetected with a rise in Alt and AST...could that be a postive sign that perhaps my body is recognizing the disease and hopefully will develop antibodies?  I thought that is what happens when a flare occurs with no increase in DNA...if my ALT and AST increased, shouldn't my dna too?

So if one is e antigen negative can't they just be that instead of calling it precore mutant?

I am a little confused.

[Jimmy1971]

I tested HBV DNA undetected (< 10 IU) last July, last year. I again did the DNA test in December the same year and the DNA was detected with 135 IU. Within 5 months my DNA jumped from undetected to 135 IU.

I am not sure if the virus has escaped the immune control and going to rise up. Could this be mutation considering the low viral load? What sort of course of action I should take at this stage. Should I go on treatment to keep the virus undetected? Or just watch the viral load and LFT's. My LFTs are all normal at this stage

I must admit that I have been stressed badly since I found out about the virus 6 months ago. Could the stress have caused the virus to be detected?

[jboyhk]

You raise the main point. Since the protocol is to not biopsy an inactive carrier at this point (risks outweigh the supposed benefit), how is one to know the state of their liver?

I guess a non invasive method like Fibroscan has to made part of the protocol for inactive carriers.

[Hepatitis Researcher]

At the time of a miniflare, at the ALT peak, DNA is often down already, as I explained above, because the immune response is now underway, clearing (low DNA)  and killing ( high ALT).

You can be eAg neg and no precore mutant. It cannot be decided on clinical grounds, only suspected. You need to test for it. But a good poercentage of precore mutant carriers are still ok, it is only one piece of a complex puzzle.

And yes, you could be on the way to clear the surface antigen and develop the neutralizing antibody. While this is a rare event - 1% per year- it does happen. It is not a well researched event - due to its rarety- but there are some reports that it occurs sometimes concomitant with a miniflare, just like the eAg seroconversion.

[ADKmtnMan]

I have been diagnosed with Hep B for just over a year now -- had two acute phases, after which no antigens developed and the Doc started me on Pegasys Interferon injections.  Into week 13 of 48 and saw my viral load drop from 165,000 to 400.  However, last blood test (two weeks ago) now shows my viral load increased minimally to 600. Dr. said he will be concerned if this is the start of a pattern of increases.  Not taking any anti-virals at this point. I am experiencing a precipitous and worrysome drop in platelets.

[Hepatitis Researcher]

Its a matter of testing expense and timing.

The HBV DNA - in reality the number of virions circulating and thereby - in the peripheral immune system , not the liver - alerting and raising a new wave of attack against hepatocytes once this number reaches a certain, individually diferent, threshold is a precursor and earlier marker of bad things to come.

Thus the HBV DNA rise almost always precedes the immune attack on the liver, that is then reflected in rising LFTs.

In chronic HBV, even the carrier state, there is, depending on remaining viral numbers and adaptive power and other important factors like current epitope structure, a constant slow evolution of the remaining viral genome from the controlling pressure of the T cell system that tries to keep it in that state. From time to time there evolves some form of immune escape - often by mutating a critical controling epitope in the core protein /e antigen system that allows the virus to expand again. This is eventually followed by a flare, that often reestablishes immune control with a new set of T cell clones against the mutated epitope.
Over time, the available repertoire of the T cell system is circumvented and the flare is not truly efficient to reestablish low/no damage immune control. Furthermore the critical intracelular production of the eAg ( despite serum eAg negativity) that supplies the visible epitopes on the hepatocyte surface is often curtailed by mutations in the region that controls e-Ag expression - the so called core promotor mutations, that gradually evolve in many (like 50%) of chronic carriers.

Thus chronic "e-Ag negative hepatitis" evolves over the years in many so called "healthy carriers" often unknown to the carrier with substantial liver damage done before action is taken. This slow evolution of HBV mutating away from immune control and the need to watch for it is not yet part of mainstay HBV healthcare practice and conceptual insight.

In answer to the question then, if you see a rise from PCR UND or very low - like 400copies/ml to say 7000copies/ml, you know that HBV is on the rise and chances for a new flare of miniflare or invisible flare ( in between monitoring times) are high. The decision to treat prophylactically with antivirals long term  in this situation (rising DNA after years of low or UND) depends - in current practice of the elite hepatologists -on the current state of the liver: With high damage present one does not want to risk additional waves of fibrosis or furthering cirrhosis. This practice might change in the future towards  lowering the treshhold for antiviral therapy once "resistance proven combos" are established and accepted and the toxicity of these combos has been shown to be very  low, even at long term use. This is likely the practice of the future.

[jboyhk]

My dr's have told me to check the viral load again only if the LFT's jump up (once you are established to be an inactive carrier).

Is that sound advice?

[Hepatitis Researcher]

If now HBV DNA is undectable you can't test for GEnotype. If there is DNA now or later , find a lab that does HBV genotyping with the Inno Lipa test kit. Some labs can also test for the presence of the precore mutant, also with yet another Inno Lipa test kit.
Again, monitoring is the key. LFTs and viral load, twice a year.Purpose: to act quickly ( using antiviral therapy)  if the virus/hepatitis comes back, which quite often occurs from the so called " healthy carrier" state. After a few years with everything "normal" patients often forget to monitor. You must be the driving force, you are potentially sick, not the Dr.. Keep it on the calendar.
Also at least once a year US/AFP to rule out hepatocellular carcinoma. Even with UND HBV DNA or even UND Surface Antigen you are still at risk for that, particular if infected at birth. Early detection is key to successful elimination, if it happens.