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.

[lila58]

I ignored this virus for 20 years,getting tests not quite every year .Two years ago I had my first viral load 1090iu/ml.I am HbeAg- ,don't have any pain in my liver but I just found that I have osteopenia in some bones,even osteoporosis in others so another thing to worry about.I take from last yearLegalon forte(milk thistle),vitD3 2000iu brand Carlson and started to take Rebuild osteoporosis formula brand Metabolic maintenance.I also take ALA 600mg and B-complex phosphorylated but I am not good in taking pills.I started to eat much healthier ,I was never a junk eater and ate pretty much homecooked meals.I don't exercise,walk sometimes and very active.Let us know about your decision.

[lila58]

thanks for the link,I am working on this.I'll have to pick one,at least i can have my tests free,wish me luck!

[Babylove0728]

I am as confused as you are, I could see. Only because it seems that my hepatologist is not that knowledgeable, and with the so many things I read online, it confuses me more.

She wanted me to start treatment since Jan 2011 with tenofovir. I held off because of toxicity to kidneys and can cause bone loss. Then I met her again in March and my HBVDNA went down to less than 10,000; so I held off again. This time I told her to check my bone density. In April ,results came back that I have osteopenia; so she recommended Entecavir.

I am still not confident so I came to this forum for opinions. Then everyone said, get fibrosure and genotype. Until now I havent gotten it yet because I do not know where to get them her in US.

Are u HBeAg-ve as well? It is really hard to start treatment. For people like us, treatment could be lifetime. Only for HbeAg+ve that treatment can be stopped at a certain point.

What do you feel right now, since u hv had this for 22 years now? Do u feel bloated somehow or do u experience liver pain?

Are you doing something with ur diet or taking liver supplements meanwhile?

[4est]

have a look on this link http://www.hepbnet.org/ maybe it will help you to chose for the 2'nd (3'rd) opinion.

[lila58]

I worked in health care in a country where hepb was spread like flu.(needle stink from a patient w acute hep b)It is the onlything that i am 100% sure about this disease.I don't want to go into details here,but i'll try to send you a pm later.I have tu go now.

[4est]

how do you know that you have infected at age of 31 ?