trial: hbsag clearance after 4ys hbvdna und and stopping tdf

[stef2011]

http://clinicaltrials.gov/ct2/show/NCT01320943

it is possible that stable nucs therapy with potent tdf or etv rescue immune response after many years or that the alt flare due to tdf stop makes cccdna unstable and clears hbv, very interesting trial

one thing is certain normal ast/alt make cccdna very stable and abnormal alt are needed to lower hbsag and cccdna fast

[stef2011]

2. Stop antiviral and wait for a flare in ALT or a flare in hbvdna or both(?), then hit the patient with Interferon.

no that s too dangerous, during alt flare you have immune system activated already no need to add interferon

to me th ebst safe way is: tdf  and then intf add on when hbsag starts to go down while hbvdna well suppresed

for those with perfect liver the stopping rule may be tried but be sure to be monitored perfectly by very expert doctors, the alt flare although very rare may also get in to liver failure

[Cjb3695]

Is there a danger in ALT flares though? Can it kill you?

[StephenCastlecrag]

You may be right. Previously, we assume Dr Gish may put you in a trial using GS9620 (TLR7 agonist). Maybe you can ask him about the trial - we all love to hear inside information :-)

[StephenCastlecrag]

This is really interesting: take Tenofovir (or any antivirals) until hbv dna is undetectable, then stop and wait for a flare?

1. A Chinese forum member jokingly made the same observation after reading about Patient 4318 who stopped tnf, had a hbvdna and ALT flare, resumed TNF and then cleared HBsAg.
2. Another Chinese forum member suggested patients with undetectable hbv dna should drink alcohol in order to kill off some liver cells with cccDNA.
3. stef2011 posted a case of a young man who took Lam when he was 20 and achieved undetectable hbvdna. Because he did not want to take LAM forever, his doctor put him on Interferon at the same time. Sure enough, he had a big ALT flare, BUT his hbv dna remained low! And he cleared the HBsAg later on.

So what does all this tell us? After achieving undetectable hbvdna using antivirals: stop and wait for a ALT flare or start Interferon?

So to have a bet each way, may I suggest a third way:
1. Achieve undetectable hbv dna using a potent antiviral
2. Stop antiviral and wait for a flare in ALT or a flare in hbvdna or both(?), then hit the patient with Interferon.

LOL. I wish we have an explanation for these HBsAg clearance cases.

[djxpress]

I have not read the study yet, but my hepatologist (Dr. Robert Gish) mentioned a study to me that Gilead was going to do that was supposed to get people off nucs all together.  He said I may be able to get into the trial.  

Maybe this is part of that study?

[stef2011]

yes i strongly agree with you and i also think the alt flare is what is needed to clear cccdna while during tnf alt are too low

i remember the old study of interferon+adefovir and that researchers noticed that those with some hbvdna not suppressed and abnormal alt had lower hbsag/cccdna than those on complete hbvdna suppression.their guess was some liver damage is needed to get cccdna unstable and reduce it faster