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.

[Babylove0728]

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.

[4est]

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.  

[Babylove0728]

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?

[4est]

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).

[4est]

good luck and keep us informed about the discussion results and decision.

[Babylove0728]

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.