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 know ,it is always a risk ,the question which one is bigger.I was infected at the age of 31,no drugs ,alcohol or other disease and yet I didn't clear the virus,must be luck!

[4est]

Increase from 20.000 to 120.000 can be a indication that treatment can be considered. Also age have to be considered and in you case also this indicate that treatment can be considered.

Treatment can be considered even if no harm is done by hvb, only for prevention.

I don't know what to say on this case if is ok or not to start treatment , but @stef2011 can have a comment on this, he have more knowledge on this.

to treat or not to treat is always a hard question.

[lila58]

HBs Ag  37845 ui/ml in 2010 and 37182,58 in 2011 .25 0H vit D 35,2ng/l in 2010 and 48,3 ng/l in2011 all at the same lab. in my east E town.The rest of tests  and the hepatologists it was in Germany.The one who recommend ed treat. said no to interferon for the HbeAg negative status but viread or baraclude.He didn,t have a fibroscan so a month later I saw a different one where I had a US and fibroscan and he said just monitor.They belong to the same teaching hospital ,so strange.In 2010  my HBVDNA was 20.000 copies at  the same lab in Germany this year.(120.000 copies)

[4est]

try als to have a look on qHBsAg (HBsAg quantitative) and also base on this you can made a decision, especially base on your expectation.

If you find qHBsAg to a low value, you can try to start antivirals until - you put HBV DNA und and after that start INF to force a seroconversion.

If you find qHBsAg at a high value you are on a the same like now, you can try or you can monitor.

[lila58]

I am 53y old infected for 22y(100%sure)living inSW US where doctors don't know much about hepb,one of the reasons i am holding treat.I saw 2 hepatologists in Europe this summer, one told me to treat with antivirals based on myHBVDNA 20.000iu/ml .The second one based on my labs ,US and fibroscan 4,2kPa,SR 100% said just monitor.He said my liver is better than his.I tried to have my genotype and precore mutants but the result came nonconcludent(it should be D).I just wanted to say that i am lost and confused like you.

[Babylove0728]

My next appt with my hepatologist is Nov 22. Which means I will have to wait for her new prescription to say 0.5mg. Almost one month of waiting again.

If you think that the difference between 0.5mg and 1 mg is very very little in potency, then I guess it is ok to take 1 mg then?

I wish my hepatologist is very knowledgeable like you. She said she is making a study about the role of antivirals on chronic hepatitis as part of her research.

If that is so, I am  wondering why she did not recommend checking my genotype and fibrosure before start of treatment. It seems that she based treatment acc to the number of years I have had HBV, my age  and my HBVDNA of 27,400 (not sure if IU or copies). Acc to her once HBVDNA on chronic HBV HBeAg-ve patients reach more than 10,000 it merits treatment regardless of ALT and AST. She also never recommended Vit D3 check.