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hbv is not Cytopathic, but some mutants selected by nucs are hence USE OF LAMIVUDINE, ADVEFOVIR and TELBIVUDINE IS "CRIMINAL"!


said in easy words, less potent nucs make hbv monsters mutants that damages our cells directly when infected........
although low genetic-barrier NAs may decrease viral load and increase survival in the short term, we predict that there may be long term detrimental effects in patients who have selected these variants. Supporting data comes from a recent study(Hosaka et al. 2010. Hep Res) where the rtM204I variant, which can cause sW196*, was shown to be a significant risk factor for the development of HCC, whilst the rtM204V variant, which does not result in truncated HBsAg, was not.

hence USE OF LAMIVUDINE,  ADVEFOVIR and TELBIVUDINE IS "CRIMINAL"!


Directly Cytopathic Drug-Resistant HBV Variants
N. Warner1; S. Soppe1; D. Colledge1; L. Selleck1; S. A. Locarnini1
1. VIDRL, North Melbourne, VIC, Australia.

Background: Treatments for CHB include antiviral nucleoside/nucleotide analogues (NAs) which target the virus by inhibiting reverse transcription. NA resistance is widespread, characterised by point mutations in the overlapping polymerase/envelope genes which encode amino acid changes in the reverse transcriptase domains of the HBV polymerase, and can encode two types of changes in the surface proteins; 1) stop codons at the C-terminal end of the surface proteins, and 2) amino acid changes that do not truncate the surface proteins. In this study we examined the pathogenicity of these variants in vitro.
Methods: Huh7, HepG2 and PH5CH8 cells were transfected with genotype D HBV infectious clones or surface protein expression constructs encoding 1) surface stop codons rtM204I/sW196*, rtA181T/sW172*, rtV191I/sW182, or 2) full-length surface proteins rtA181T/s172L, rtA181V/sW173F, rtM204I/sW196S, rtM204V/sI195M. HBsAg expression and secretion were measured by Western blotting and quantitative serology. Proliferation, apoptosis, and intracellular HBsAg levels of transfected Huh7 cells were measured using flow cytometry up to 5 days in culture.
Results: HBV variants encoding surface stop codons were completely defective in HBsAg secretion, which could be partially rescued by co-expression with wt HBV. HBV encoding full-length surface proteins were secreted from the cell with varying efficiency. Flow cytometry was used to show that the truncated surface proteins accumulated to high levels intracellularly. Cells transfected with these stop codon variants had low levels of proliferation and high levels of apoptosis. The most cytopathic variant was rtM204I/sW196*, followed by rtV191I/sW182* and rtA181T/sW172*. This cytopathic effect was shown to be directly due to expression of the truncated surface proteins. HBV encoding full-length surface proteins had wt levels of apoptosis, proliferation and intracellular accumulation.
Conclusions: HBV surface stop codon variants selected during NA therapy accumulate inside, and are directly cytopathic to the host cell, causing apoptosis. Apoptosis and chronic liver injury are strongly associated with disease progression and the development of HCC. Hence, although low genetic-barrier NAs may decrease viral load and increase survival in the short term, we predict that there may be long term detrimental effects in patients who have selected these variants. Supporting data comes from a recent study(Hosaka et al. 2010. Hep Res) where the rtM204I variant, which can cause sW196*, was shown to be a significant risk factor for the development of HCC, whilst the rtM204V variant, which does not result in truncated HBsAg, was not.
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Avatar universal
There are flow of cytometry  immune tests.. I had those done.. They were looking for HIV in me, I pressed them on.

Is nagalase levels test available in the US?

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Avatar universal

we live with millions of virus, retroviruses and bacteria in us, we are 90-94% not human cells and only 1-4% human cells, this is why it is useless to test for most viruses, we just live in a balace with them and cooperation since many of them allow us to live

what you do need to test is immune system health because this is how we live in balance with viruses/bacteria and diseases but unfortunately there are no tests to measure immune function and those we have mean very little

testin for:
vit d levels
nagalase (less than 0.6 means macrophages work checking our body for pathogens, if more than 5 macrophages can be activated, immune system is blind and immune suppressed)

a part from those tests if you never get sick and never need drugs your immune system is working.
cd count tests, wbc counts are not useful because it is not the number of cells but quality to allow immune system to work.you can have all high numbers but high nagalase so all cells not working
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Avatar universal
I have tested myself for just about all the viruses. Many doctors think I am crazy, but I did a very thorough evaluation of myself.. partly because of that black hairy tongue that after your recommendation has gotten better.. This what else I have antibodies too..

CMV, EBV, ParvoB19, Micoplasma Pneumonia, Toxoplasma. CMV does stress immune system by itself.

Infectious disease doctors tell me that most people have being exposed to these to and to not to worry about. But how do Herpes virus such as CMV and EBV interact with HBV remains unknown and what they do to the immune system that perhaps develops a lag of response to HBV

And this is what researchers should be studying. Instead you see what is going on this side of the pond. Long product testing on  very few people of the drug that can help us.

This is very frustrating..
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Avatar universal

they use combos of highly toxic drugs much diiferent from us, we may look at them just for the sides but since we use tdf mono or etv mono we are very very far from the sides experienced by them

i also dont think hbv can stay after 10 years of tdf or etv if we add intf, it is a fact that hbsag lowers after years and years of nucs and intf add on can just fasten this process
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Avatar universal

gallo under trail in australia admitted hiv was never isolated and less than about 40% of ptients dying of aids had positive hiv tests, so hiv equal aids was never proven.

aids is caused from unhealthy life styles, drugs use, chronic infections of many viruses/bacteria, damage of malt mucosa, chemicals in food....never look at hiv research because there is nothing scientific and much markting in that filed
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Avatar universal
Exercising and etv. I try to swim daily to keep muscle loss from taking antivirals to a minimum. And to also oxygenated my body better. Generally i can swim ok on etv. But of course being off the medication the work outs go much easier. Heart rate is less. So that is another thing of antiviral drugs that are not addressed at all.  HIV infected people report also elevated blood pressure from nucs taken for a  period over 3 years. Anybody has any comments about it?
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Avatar universal
A word about Etv from my experience living with core promoter mutant. It.suppreses it well. But as soon as i stop it the virus comes back strong again.

Also as a possible  side effect my hair have stopped growing. It is not falling out or anything just not growing. I need haircut like once every six months now.

Also i have developed elevated blood pressure on etv. Something Hiv folks report as a side effect of taking nucs for a long time.

Also  i had sunlight sensitivity from etv.  And cannot stand the hot weather now. My skin turns red and body gets very hot. So i have learned to manage it and avoid being out on the sun  for too long.

Also etv caused me to have headaches - migraines to be exact when I started it taking 1 mg daily. 0.5mg was ok.  
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Avatar universal
Stef. Which researcher you have corresponded in LA? I cant locate one to work with me. Those  that call.themselves researhers do product testing for a drug  company/s rather then unitilize available treatments.
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Avatar universal

tomorrow i am rechecking hbvdna, it can be that stopping alinia i just got some hbv between 1-5iu/ml and it just got und again now
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Avatar universal

580000iu/ml, but it is the mutants to define response, only very high hbvdna at 10*7-10*8 needs combo sometimes,

in 1 month it got to 3400iu/ml so it just a matter of low level mutants

And how long have you been on entecavir?
2 years

you feeling better now than before you started with your anti viral medications?
of course i do but it wasn t entecavir to make me feel better but heptech products and gcmaf, of course these two work better when hbvdna is und but without them i dont think entecavir alone would have regressed my cirrhosis so fast
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Avatar universal
Hello Stef,

How much was your HBVDNA when you first started with your anti viral treatment of 0.5 mg of entecavir? And how long have you been on entecavir? Are you feeling better now than before you started with your anti viral medications?
Thank you.
Helpful - 0
Avatar universal

as LA researcher said in mid 2010, etv is only partially active on me and ntz probably suppressed the mutants

it can also happen to have some hbvdna detactable from time to time for others and it is not dangerous if it goes und again the next month, but in my case i prefer no risks
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Avatar universal

studies from drug manif are done to fit data in order to maximize sells, they are not done on patient's sake focus

the hbvdna in the serum must be as low as possible, they used 50iu/ml at the time of the study just because there were some old machines with that bad sensibility

my point is making hbvdna und as much as possible in the liver, not in the serum.if you hve so much hbvdna you rik resistance because it is much more in the liver, infact my alt are always abnormal (by the way the study also uses alt normal 40 or 45, a piece of cake to boost good results doing like this)

in my case, cirrhosis, there must be no hbvdna and normal alt as soon as possible, to my point of view this antiviral has been a total failure, if it wasnt for hepatitistech antioxidant therapy who knows how my liver would have been
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Avatar universal
I mentioned a study conducted by Bristol Myers on entecavir monotherapy versus ent plus tnf.

Just try to goolge-search "study by Bristol Myers on Entecavir monotheraphy". The results came out just 2 days ago.
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Avatar universal
Did your doctor followed up by increasing your dosage to 1mg from 0.5mg you were taking?
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Avatar universal
Hi Stef,

Sorry to hear that you think ent was a failure for you. However, 20IU/ml is not bad, isnt it? In one study I read conducted by the drug manufacturer (Brsitol-Myers) they were discussing HBVDNA of less than 50IU/ml and for them that was undetectable, after 96 weeks. The study compared ent monotheraphy and  ent plus tnv on nucleoside-naive chronic HBV HBe Ag+ve and HBV HBeAg-ve patients . I am trying to look for the link so I can post it here. I read it last nite.

How long have you been taking ent?  Although  your result of less than 20IU/ml is still undetectable to some labs.
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Avatar universal
Hello 4est,

I did see my doctor last Wed Nov 9th and I asked her why she prescribed me 1mg ent as opposed to 0.5mg recommended by the manufacturer of Ent (Bristol-Myers) and her answer was: "that is the dosage recommended by American Liver Association."

Then I told her that the drug manufacturer suggests 0.5mg for nucleoside-naive patients like me and she said," one can do 0.5mg or 1 mg" ; however she said "here, (meaning the hospital where she is), we give 1mg following the Amer Liver Assoc."

Obviously, 1mg will be more potent and since ent has an issue of resistance, (small) compared to tnv, which has none so far, then maybe 1mg will work better? I hope and pray.

Then I asked her if it is going to be toxic and she said "NO".

I have to start treatment at some point, and it has to be soon. I have waited long enough holding off treatment which I should have done beginning of this year;  and I think I have gotten enough answers to my questions and issues, and I must do something now to lower my viral replication, regardless of whether I am confortable with it or not. No matter what I do with my diet, no matter how much liver support supplements I take and no matter how much vitamins and antioxidants I take, it looks like it will not lower the viral replication. Virus has a mind of their own and it will continue to make "copies' and it is scary, unless we do something to put it under control.

With God's help, I hope I am able to tolerate this medication that at this point in time, I cant overlook and hold off anymore.
Helpful - 0
Avatar universal

vitamins/antiox dont interfere with antivirals, except maybe milk thistle, you better restart it when hbvdna und

as to etv it has been a failure on me and i will be swtching to tenofovir soon, probably combo.as i lowered nitazoxanide hbvdn is back detactable although less than 20iu and alt is 35

if you start etv better use 1mg dose, as i have always thought it is less potent than tenofovir
Helpful - 0
Avatar universal
Hi Stef,

Maybe I missed most of your posts because I have been here only since early Oct. What did you do/eat to get rid of fatty liver?

With the so many vit/antioxidants you are taking, how do you schedule them in such a way that they dont interfere with each other along with your combo antiviral treatment?

Are you able to split a 1mg entecavir pill to get a lower dosage of 0.5mg?
I thought that as you advised that I should be on 0.5mg and I think that I will be more comfortable taking 0.5mg because that is the dosage recommendation by Bristol-Myers for nucleoside-naive patients (like me), and 1mg is for lam resistant patients who are trying to switch to ent. If it is alright to split the 1mg ent I have, I will do so and start the treatment today , I am thinking at 4 p.m. (2 hours after my lunch and 2-3 hours before dinner). When do you take yours? They say to take it 2 hours after and before a meal.

THank you as usual. Your extensive knowledge has been of great help to everyone.
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Avatar universal
no, I'm not on antivirals.

My HVB DNA is around 100 UI/ml and the other result are good (you can see my results at http://www.medhelp.org/posts/Hepatitis-B/My-result/show/1568816?personal_page_id=2249050) so is not need for antivirals consideration in my case.  
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Avatar universal
Yes. I read about red rice also. Maybe I should try that too. But I would like to recommend you to google-search about "miracle drink". There are 2 versions which are I though equally good: juice 1 carrot, 1 beet, and 1 apple OR 1carrot, 1 potato and 1 appleand drink it with an empty stomach in the morning when you wake up. Then you can have breakfast after an hour. We cant go wrong on this "miracle drink". We eat these vegetables and apples on a daily basis. Only we are taking these in the form of juice. Absolutely, there wouldnt be side effects nor toxicity, BUT only health benefits. Beets for one along with carrots, are really very very healthy. SOme others include cucumbers and celery in the juice.

Are you also on anti viral meds?

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Avatar universal
good luck with your doctor and keep us informed about the discussion results and decision.

as regarding the rice, I notice that you mention brown rice, maybe you should try read rice (look for red rice in this website).
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Avatar universal
good luck and keep us informed about the discussion results and decision.
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Avatar universal
From te time Iw as diagnosedin 2000 till June 2010, my doctor said I did not need treatment with HBVDNA at 1780IU/ml and with normal ALT (below 2X UL of 19, i.e. below 38) and my ALT till now has always been 31 and below.
However, she wanted to start me with treatment since Jan 2011 when HBVDNA started to replicate for 6 consecutive months. The latest being 27400 in July 2011.
The only hesitation right now is the dosage, Her prescription was 1mg and website on entecavir says 0.5mg for nucleoside-naive patients. I thought for first-time treatment from what I have read is 0.5mg and 1mg for those who were on diff antivirals bnefore who became resistant to it i.e.those who used lamivudine and became resistant and switched to entecavir has to use 1mg.
I wil ltry to see my doctor tom even tho my appt is still 3 weeks from now to ask why 1mg. Otherwise I am really leaning on starting with treatment. After so much hesitations and reading I thought we should lower the viral count in our blood and at this moment in time, only antivirals it seems like can lower it. I dont think that at this point diet will help. HAving a well-balanced diet will certainly be good for the liver, however I dont think that it will lower viral replication. Even with treatment, liver is still infected but my doctor told me that if I were her family, she should start treatment. When I have always expressed concern about hesitation with treatment, she asked me why do I want the virus in my body. I thought that diet can lower replication and it looks like not maybe because of age and immune system.She recommended entecavir because of my osteopenia.
Besides avoiding fats and red meat, I try to juice an apple, a carrot and a beet when I wake up in the morning and drink it with empty stomach. Try to google-search "miracle drink" and see if this will be beneficial. I thought there is no harm to drink this. Vegetables are good for the liver, besides being cancer-fighting foods. I eat brown rice instead of white and whole grains and whole wheat bread instead of white. Also, I try to avoid sugar. I eat fish esp salmon which is a very good source of Vit D, but very very seldom meat. They say to eat plenty of carbohydrates for energy and foods that are easily-digestible.I also read drinking water with freshly-squeezed lemon 3X a day is good for the liver, as well as juicing fresh oranges 2X a day and drinking it with empty stomach. I also line-dance as my form of exercise and a lot of walking. I live in NY and we do a lot of walking here. I never drink. not even white wine nor red wine, altho red wine is healthy for the heart. Never smoke either.
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