Ultra deep sequencing

[Bob0620]

Do you guys have this test. It's not common ah hospitals.

Purpose is to detect viral mutants. Better than standard testing

Link : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327662/

[stef2011]

keep in mind that no mutants until now made resistance on tdf and the drug worked even with a194t.this is due probably to the fact that tdf stays in the cells for very long time and at high quantity.this said, i d go with etv+tdf if such mutation was present

there is only one case of no response to any antiviral in a patient who developped so many mutations (primary and secondary) doing monotherapy with all nucs and failing and it is thought the combo of both primary and secondary made non response

[Bob0620]

I got an email form the reseacher :

Thank you for your comment.
In our study, the mutation resistant to tenofovir(A194T) was detected in only one of 14 chronic-naive patients.
These results suggest that the mutant HBV clones comprising tenofovir-resistant mutations could latently exist even in the NA treatment-naïve cases.

[stef2011]

all useless on hbv to lower hbsag, truvada is very old, it has a lot of sides longterm especially on kidneys
it was all just marketing and crazy to use on healthy people and it doesn not cure hiv eather

[Bob0620]

Thanks for the info. GS 7340 ( new Tenofovir ) look promising too.

[StephenCastlecrag]

Yes. Embritiacibine is in phase 3 for HBV. It is the recommended combo in the event of resistance to Tenofovir.

[Bob0620]

Tenofovir + Embritacibine just approved for HIV. Do you think it can used for HBV ?

[stef2011]

if your doctor agrees the best is add on 4-8weeks and then slowly discontinue etv

[stef2011]

i dont know you have to talk to your doctor it depnds if had response already to it

[new_hepb]

I started treatment with entecavir for last 1 month. Can I go on tenofovir now?

[StephenCastlecrag]

I read the paper. The results are consistent with
1. treatment naive patients have a variety of mutants, so it could explain why antivirals may not be effective or become resistant quickly for some patients as they have mutants even before treatment.
2. Entecavir is more effective against G1896A precore mutants.

As for explanation why natural eAg serconversion occurs, the result is a bit confusing. The scientists still believe it is due to precore/ core-promotor mutations, but believe some other mutations are also involved. I hope this type of research can provide a mire definitive explanation why natural eAg seroconversion occur and why some go on to develop HBeAg negative chronic hepatitis.

[stef2011]

meanless to us of course drug makers have their intrest in both resistance and use of other nucs

[stef2011]

Results
Most genomic changes observed in viral variants were single base substitutions and were widely distributed throughout the HBV genome. Four of eight (50%) chronic therapy-naïve HBeAg-negative patients showed a relatively low prevalence of the G1896A pre-core (pre-C) mutant in the liver tissues, suggesting that other mutations were involved in their HBeAg seroconversion. Interestingly, liver tissues in 4 of 5 (80%) of the chronic NA-treated anti-HBe-positive cases had extremely low levels of the G1896A pre-C mutant (0.0%, 0.0%, 0.1%, and 1.1%), suggesting the high sensitivity of the G1896A pre-C mutant to NA. Moreover, various abundances of clones resistant to NA were common in both the liver and serum of treatment-naïve patients, and the proportion of M204VI mutants resistant to lamivudine and entecavir expanded in response to entecavir treatment in the serum of 35.7% (5/14) of patients, suggesting the putative risk of developing drug resistance to NA.

[StephenCastlecrag]

A most interesting paper. We may be one step closer to explaining natural seroconversion of the eAg.