HBe seroconversion

[chanthou]

Please help interpret this lab result for my mom:

She was hbe seroconverted in December 2008. HBV dna undetectable since September 2007. Now her HBeAg is negative S/co = 0.30 (S/co1) [Technique MEIA; AxSYM].  Does this mean HBeAb is too weak to maintain seroconversion status? (Since it is very close to zero?) Will HBV relapse soon? (She is on Entecavir 0.5 mg; before she took 1 mg/day).

[stef2011]

The second doctor said she was never resistance because her HBV DNA was always undetectable
this is very ignorant said from a doctor, resistance and hbvdna as i said before is easily possible since the mutant is less potent than wild type and will take years to break up and make hbvdna detactable, usully secondary compensatory mutations appear to improve hbv replication.

at this point the best choice would be tenofovir which is much cheaper and much potent with no resistance detected until now, also nitazoxanide should work preventing resistance but i don t suggest that for this purpose since we only have in vitro studies and no in vivo trials about prevention of resistance
tenofovir has also a generic called tenvir (about 99usd), tenofovir is also sold at about 10usd or less per bottles in poor asian countries where the generic tenvir is taking all the market, if you have access to asian contries i have seen prices between 7-10usd

The question is whether she can stop entecavir now and go with Teno alone because entecavir is very expensive.    
there is no data on entecavir resistance blocked by tenofovir and it is not known if tenofovir can keep hbvdna for long so she absolutely must keep that combo, if she is hbe negative she can add nitazoxanide and hopefully clear hbsag in 1-2 years

we have this data about lam resistance:
1) entecavir useless and much less potent than the other options below
2) lam+adv, much more potent than etv, no other resistance mutations development
3) tenofovir, best choice and if doesn t get hbvdna und tenofovir+ftc, no other resistance mutations development

since trial found that lam+adv is more potent than etv or adv monotherapy i think that it is better to keep etv+tnf

if you check in the community there is also a generic for etv made in india and i'd definitely choose tnf+etv+ntz

[chanthou]

Actually my mother took LAM in January 2007. Her initial HBVDNA was 5 millions copies.  In April (3 months later) it was down to 800 copies. Then in September 2007 another test showed that HBV DNA was not detected (less than 500 copies).  And since then she continued to be undetected until now (with more senstive machine she has less than 6 UI/ml).  The doctor changed to 1 mg baraclude because LAM did not cause HBeAb postive after on year (although HBeAg became negative; HBeAb was on borderline between postive and negative--they say doubtful). He said LAM was not working or became resistant (we didn't have resistance test).  And after 3-month baraclude her HBeAb became clearly positive. The second doctor said she was never resistance because her HBV DNA was always undetectable. Because of cost we asked whether she can take 0.5 mg.  That is why he change to 0.5 mg (saying 1 mg is given to people who have problem with LAM). Thank you.

On another question: my friend was apparently resistant to LAM and then Entecavir (HBV DNA lowered for a while and then climbed to 30,000 copies/ml).  The doctor asked her to change to Tenofovir.  My friend took Teno and Entecavir 1mg per day.  After 5 weeks she becomes undetectable. The question is whether she can stop entecavir now and go with Teno alone because entecavir is very expensive.    

[stef2011]

no now resistance cannot be done, it needs hbvdna high, when i made the test i was 135iu/ml and they used an assay used for research so they could see only population >20%, this test detect mutants>5% population but hbvdna was too low

in any case they are not sensitive enough i have see a research on lam and adv users with hbvdna und and normal alt, more than half of them on biopsy had the mutants in the liver and the wild type in mononuclear cells in the blood, this is simply to say that mutants take years to make hbvdna detectable and that lam and adv are not safe at all

also changing to 1.0mg is useless latest hbv congress in vienna said that etv cannot be used on people that used lam despite resistance detected or not because it will lead anyway to resistance sooner or later, the only safe alternative is tenofovir

thay have found tht the very little percentage of people not developing lam mutants (about 10%) are those who get hbvdna und by 4-12weeks, if your mother did so probability of no resistance is high

also my mother used lam but she had inteferon first so she got hbdna und by about 4 weeks then after about 1 year had transplant so now hbsag is negative, she didn t develop resistance thanks to hbvdna und in 20days

[chanthou]

I will take her to have resistance test on Saturday and I will let you know. If resitance is found, then can she continue with the 0.5 mg baraclude?

[stef2011]

if i were you i'd go for combo or cccdna biopsy, this might sound exagerated to doctors but i bet they would do this if it was his son since how can you see if there are lam mutants?

i also see they discuss hbeb pos or neg...this has nothing to do with mutants which are often present even before therapy (hbv generates mutants all the time it can be the same mutant to drugs or not).
i have been found rtq215s mutant before therapy so it is not difficult to have them baseline.
only tenofovir has never been found with resistant mutant both naturally or on therapy (only 2 cases but hiv+hbv so it cannot count hiv has many immune system problems with hbv)

[stef2011]

i know this very well since it is my main problem....
On ultrasound, her liver looks grainy.she has severe fibrosis, i guess grainy can be small regenerative nodules (liver is regenerating but these small nodules increase cancer risk, they will get away with time)

(Fibroscan = 10.2 Kpa), values higher than 10kpa are at increased liver cancer risk like in cirrhosis, she needs a healthy diet and total supression of hbv like in cirrhosis.reistance can be very dangerous like in cirrhosis and worsen what she has regressed by therapy.
check alt, hbvdna, hbcab igm<0.08s/co closely or start a combo of etv+tenofovir to prevent resistance as close as possible to 100% but only if she has no lactic acidosis problems and no kidneys problems

bluberries (153gr per day) and black rise has shown to reduce fibrosis and also 2-3 cup of coffee per day

it is reported that etv regress fibrosis greatly in 3-6 years time so as for my situation your mother will regress all this damage, once she is below 10kpa she has no more worries
it is very important to prevent resistance in this situation like for me on cirrhosis, cirrhosis starts from 12,5kpa, i am at 13,9 and hopefully decrease 2 points by october (lready dreased 2,5 points from march)

my god how can they say she is not resistant without a mutation test?etv should not be used on lam users because lately it has been found inefecctive even at 1mg since resistace develops by time (56% by 5 years).Resistance is registered in cccdna only cccdna by biopsy or hbvdna test can say if resistance is present

having such severe fibrosis i'd never risk on etv, i actually don t want to risk on myself because resistance test detects only populations over 20% so i will combo

the bad side of combo etv+tnf or tenofovir mono vs etv mono is possible kidneys damage in less than 1% but making blood tests you can see before kidneys damage happens and change drug dose or drug while if resistance happens you cannot reverse it

[chanthou]

Thanks, Stefano.  She is undetectable (lower than 6 UI/ml on Cobas Taqman). On ultrasound, her liver looks grainy. (Fibroscan = 10.2 Kpa). Last ALT 29 UI/l. She changed to 0.5 mg because doctor thinks she is not resistant to LAM (She was undetectable on LAM since 2007, but in 2008--one year after her HBeAg was negative, but HBeAb is + or -. So the 1st doctor thought she was resistant to LAM although HBVDNA was undetectable at the time. So, he asked her to switch to Baraclude 1 mg. After 3 months on Baraclude the lab result became clear: her HBeAb became +.  Then, she continues Baraclude 1 mg until recently.  The second doctor said that she was not resistance to LAM so 0.5 mg Baraclude is enough. Then, she has changed to Baraclude 0.5 mg.  Her HBsAg = S/co = 4713 (before it was 4900).

[stef2011]

is alt lower than 19?hbvdna pcr has sensitivity 1-10iu/ml?

[stef2011]

hbe seroconversion by antivirals has no meaning in terms of stopping therapy but it is a sign hbsag and cccdna are decreasing, she must continue therapy until hbsag become negative

that is a good sign and hbsab will appear by time but that is not important hbv eradication happens also without hbeab.
she is also lucky because hbsag gets low on hbe positives and hbsag seroconversion happens at higher rates than hbe negatives

why was she changed to low dose 0,5mg?did she have lactic acidosis or renal damage?
the trial with 1.2% resistance at 6years is on 1,0mg dose not on 0,5mg dose (0,5mg dose first year then all switched to 1,0mg dose)