"..the majority of virions released at a low production like under antivirals is locally absorbed onto hepatocytes and never reaches the circulation. Thats why the UND viral load is so misleading."
So do you agree with AASLD's practice guidelines for treatment criteria of hbe- Hep B? And the difference between chronic hbv and inactive hbv? (Or would you add/emphasize something else (tests like fibroscan, or even invasive ones like biopsy) in addition to the usual ALT, ultrasound and HBVDNA?).
Thanks
sorry typing error
10 oct 2012 hbsag 4396iu/ml
used architect with automated quant kit for both tests, no sample diluition
it is interesting to note that between 10 oct 2012 and 16 oct 2012 i used daily suppository of imiquimod 12.5mg and had tests among these close dates (but just had results on hbsag 16 oct now):
10 oct 2012 hbsag 43696iu/ml alt 44 creatinine 0.7, started imiquimod daily suppository for 9days
16 oct 2012 hbsag 3681iu/ml hbvdna 31iu/ml alt 42 creatinine 1.2
21 oct 2012, stopped using daily suppository and switched to weekly suppository 25mg which showed no results until i stopped definitively on early jan 2013 and started ezetimibe
if imiquimod is to be ever tried by others or me daily suppository maybe the best schedule although inflammation is high from creatinine increase, fever was not high just 37.5°
i have been using about same time daily (just forgot totally ezetimibe one day)
i ll use iber every day exactly same time or if necessary even 30min in advance and recheck bile acids few hours after taking it
imiquimod did make inflammation fibroscan increased from 4.5kpa in october to 4.9kpa instead keeping constant decline as previously
i ll also keep etv+tdf, the local prescribing liver specialist prefers the combo too he wants to stay on the very safe side
thank you so much for your help
So it looks like the ezetimibe was not realistically working on entry inhibition,
or more precisely to block the NTCP in a reliable 24 hours fashion. Your biliary acids were very low, which shows that there is no blockage of the HBV receptor. You have to consider the pharmacokinetics of the ezetimibe and possibly also the irbesartan. Blockage is only effective if it is a 24 hour continuous affair. If you leave the door open for the rats just one hour a day, your house will be filled with them.
to see if the irbesartan does a better job in vivo, you can simply measure your bile acids now after you take it. Considering the intense dynamic of the bile acid re-circulation ( 15 grams are recycled about 10 times per day!) any effect of blockage will be rapidly noticeable as an increase of circulating bile acids. That level might also change dynamically in response to various level of blockage of NTCP as the drug levels in blood will vary due to the drugs pharmacodynamic behaviour.
In other words, they might increase an hour after irbesartan, only to decrease to baseline 3 hours later. This needs to be considered in order not to interpret the values naively.
Under Myrcludex full blocking dose, the bile acids go up quite dramatically but its effect needs to be maintained 24 hours also, since obviously partial time entry inhibition is ineffective. Virions can wait in line until the doors open again, even if only shortly within 24 hours.
Regarding blip of DNA positivity after imiquimod:
If there was a temporary increase in liver inflammation, it could reflect the temporary increased lysis of hepatocytes. The intracellular virions are by far more abundant than the ones released into the circulation and also, very importantly, the majority of virions released at a low production like under antivirals is locally absorbed onto hepatocytes and never reaches the circulation. Thats why the UND viral load is so misleading.
But you could have a temp release of intracellular virions by lysis, causing the blip.
The Pisa researchers are incorrect in saying that ENT plus TDF is less potent to suppress replication than TDF alone.
While it is fundamentally true, that the lack of synergism or even very effective additiveness among antivirals is caused by competing for access to the polymerase binding site like several cooks in a tiny kitchen, there is a slight measurable degree of additivity between TDF and ENT, when you have a clean and clear model situation to address that question.
I know of a research situation, where in a particular patient a successive exchange between TDF, then ENT, then TDF plus ENT was performed.
it was also repeated to confirm the findings. It was measured with a research only ultra high sensitive quant assay. The results were clear: TDF alone was slightly superior to ENT alone, and the combo was clearly superior over both monos, almost one log further reduction compared with the monos.
Technically the antivirals have different efficacy on the three block-able modes of the polymerase; Priming, reverse transcription and extension of the incomplete plus strand. ENT is the only one that effectively works on the priming step, but TDf is better in RT and single strand repair mechanisms inhibition.