of course, HBsAg neg = much less virus (close to zero) = much less mutation chances
Thanks
Obviously being geno type C with mutations is riskier.
But HBSAG 'Non Reactive" reduces the chances of mutations?
Even with a pos antibody level, there will be remnant virions produced in the liver.
HCC risk will be reduced if precursor clones are diminished, which typically produce hbsag - not always virions in case of integrated hbv sequences.
But a pos antibody is a strong sign that the remaining hbsag production from all these sources is minute.
Hi Studyforhope thanks
"The undetectable status of the pcr blood test DOES NOT MEAN that no more virus is produced in the liver. It means that the small remnant amount is absorbed and internalized mostly directly in the liver"
So in regards to the above comments even if hbsab are produced does it mean there is still remnants absorbed into the liver?
But would I be right in assuming it dramatically reduces the chances of HCC with hbsab rather than without? like a resolved acute infection for example?
We cannot say at this point if TAF or TDF is more potent in the induction of a hbsag loss.There are good reasons to think that TAF is more potent in the hbv replication inhibition in the liver.
Both substances are just chemical precursors that have to undergo critical transport processes, stability issues while en route to the hepatocyte cytosol and enzyme mediated processing to the final metabolite that enacts the actual inhibitory action on the hbv polymerase :TENOFOVIR DIPHOSPHATE.
NakedTenofovir itself can barely enter the liver cell and is therefore almost completely filtered away in the kidney glomerula, where HOWEVER it is afterwards actively absorbed into the proximal tubuli by a special transport mechanism unique to these cells. That is the reason for its accumulation in the tubuli cells with the resultant toxicity for the kidneys.
Tenofovir disiproxil fumarate, the actual chemical in the viread pill is absorbed in the intestine at a decent about 50% efficacy.
When it enters the bloodstream and reaches the liver via the portal vein, it immediately starts to fall apart with a fairly short time constant, slow enough thankfully that a small portion of INTACT TDF will touch the liver cells and then be absorbed to the inside, where it's further processing via 3 steps to TENOFOVIR DIPHOSPHATE will start.
All the other TDF will dissociate into naked TENOFOVIR that cannot enter the liver and is eliminated in the kidney.
TAF is fundamentally different in its pharmokinetic behaviour in that it is STABLE in the blood stream and will enter the the liver and other organs with ease, LEADING MOST LIKELY TO A SUBSTANTIALLY HIGHER intracellular concentration in the hepatocytes and after the 3 further processing steps will achieve a HIGHER FINAL CONCENTRATION OF TENOFOVIR DIPHOSPHATE in the cell, with a higher inhibition of the hbv polymerase and a resulting slowdown in the remaining synthesis of new hbv dna and virions.
The problem with all antivirals is that the synthesis inhibition is not truly complete, leading to a much slower but ongoing reinfection, therefore no cure, no true dry up op virus production.
The undetectable status of the pcr blood test DOES NOT MEAN that no more virus is produced in the liver. It means that the small remnant amount is absorbed and internalized mostly directly in the liver.
In summary, it is possible that TAF leads to substantially higher TENOFOVIR DIPHOSPHATE concentrations in the liver, despite its dramatically reduced dose of 25mg vs 300mg, which might further result in a smaller remnant virion production and consecutive reinfection of neighboring liver cells so that immune mechanisms operating simultaneously might have a higher chance of catching up and reducing the total amount of infected liver cells better than TDF.
But I have to say "MIGHT" because we cannot directly measure these metabolites and infected cell numbers in a human trial. All we can do is follow surrogate markers like serum hbv dna and hbsag.
It is also possible that the potent advantages of TAF over TDF are mainly lost due to the dramatic dose reduction.
What is quite certain however is that a huge reduction in the kidney burden by NAKED TENOFOVIR will occur with the small TAF dose, and that would in itself be progress towards the kidney and bone problems that , to a small but obvious degree are burdening the long term use OF TDF in some patients.
Stef whats your thoughts on the vit d supplement i posted the link for?