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

[stef2011]

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.

[stef2011]

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

[Babylove0728]

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.

[Babylove0728]

Did your doctor followed up by increasing your dosage to 1mg from 0.5mg you were taking?

[Babylove0728]

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.

[Babylove0728]

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.

[stef2011]

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