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.

[veteranB]

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.  

[veteranB]

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.

[stef2011]

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

[stef2011]

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

[Babylove0728]

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.

[stef2011]

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