Drug resistance

[chanthou]

My friend has hepatitis. First, she was treated with Lamivudine, then changed to Baraclude 1 mg/day. 15 months later she was tested HBV DNA 400 copies/ml normal ALT (around 20 UI/l); 3 months later HBV DNA rose to 1,000 copies; another 3 months later HBV DNA rose to 2,000 copies.  Her ALT remains always normal.  Is she resistant to Baraclude or it is normal fluctuation of viral load? Does she need to change medication?

[sima5678]

i had taken hepatitis b antidote in 12 years ago,,,but since 2007 i have physical relationship(non-protected sex) with my partner,,he has hepa b(chronic),,,is there any chance of infections????plz help

[stef2011]

she might also boost immune system by diet by checking blood levels for vitamin D and selenimum and zinc
if deficent she can start organic supplements or check diet for selenium and zinc.vitamin d is from moderate sun exposure

selenium optimun levels 130-150
zinc 900-1200
vitamin d 50-60ng/ml

[stef2011]

She is 23 now. my god they didn't do one thing right, antivirals must not be started at young age

Are you on this combination tenoforvir + NTZ?no iam on entecavir+ntz, we have started entecavir by change nov 2009 without genome resistance test.it was a lucky choice since later when i went to the research center in pisa they cheked evrything and i have rtq215s mutation which might lower tenofovir response in theroy (there is no in vivo data on this mutation only since patients with this mutation also have all lam mutations)

How is it?no sides and everything ok for me

We would like to try ntz and tenofovir. But, we don't know if the doctor here will prescribe NTZ because it is not known her
well of course start tenofovir or interferon according to choice of a new expert liver specialist, at young age interferon is a good choice, is she hbe negative/hbeab positive?also combo ntz+interferon looks like dynamite

as to the prescription it is not necessary ntz is so light as sides that some countries do not require prescription, some in our group boguht it without prescription, send me a private message so i will let you know where they bought it.
in mexico prescription is not required but the price of ntz called daxon there is high 25usd for 6pills vs 204usd for 180pills with nizonide500 from lupin, so it is better i will tell you where to buy nizonide

ntz allowed on babies 1year old, i don't think there are many medicines so light as sides, even aspirin is heavier.plus i ve seen they started a trial on advanced cirrohosis for encephalophaty so there is no worry for that.on the contrary tenofovir must be started with prescription and kidneys function tests

NTZ can cure or just stop progress liver damage.
ntz can eradicate hbv in a high percentage of patients higer than all other drugs on hbe negative, it will make hbvdna undetactable in a couple of weeks and all liver damage will be stopped

she has no liver damage so flares are not an issue until 1000-2000 but she won't have any if she startes ntz before hbvdna gets higher

remember to start ntz before tenofovir because if hbvdna is undetactable ntz will work much less.i suggest to use same strategy as on hcv trials, 4-12 week ntz lead in and then add tenofovir

also consider she doesn't need to make any special diet on f0 liver damage she has the same liver as healthy people without hbv but of course hbv must be stopped to prevent this damage

[chanthou]

Hi cajim,

What do you mean by nutrition, rest and no toxins?
What do you suggest for:
1.  Nutrition?
2.  Rest? (not working hard? How many hours sleep to be enough?)
3.  No toxins (what should be avoided?)

Thanks.

[chanthou]

Thanks, cajim and stefano. She is F0 on fibroscan. She is 23 now.

Are you on this combination tenoforvir + NTZ? How is it? We would like to try ntz and tenofovir. But, we don't know if the doctor here will prescribe NTZ because it is not known here. We don't want to take medicine without proper prescription; if something happens, we don't know how to correct it.

She will meet the doctor again mid-July and will tell him about your suggestions.  NTZ can cure or just stop progress liver damage.

By the way if flares occur, do you know how to cope with it?

Best,
Chanthou

[stef2011]

for example my sister has same situation as me but made interferon while sperimental about 15-20 years ago so she prevented all liver damage so she has no rush
she doesn't want any therapy but ntz since the only one free of sides and more potent than nucs and interferon on her

so she will keep high dose 2g daily ntz and check hbsag every 6 months since hbvdna und since 3rd week of ntz

[stef2011]

i will try it for these resons:

it is known to be the best to prevent liver cancer and even if i get hbsag negative liver cancer is still a risk when on cirrhosis

i am followed in one of the most advanced research center in the world with all tests to follow every detail so it is ok to do it plus interferon is ok on early compensated cirrhosis, it is uncompensated or advanced cirrhosis that is very risky for the alt flares

interferon makes damage on cirrhosis because it activates immune system which kills infected cells and makes alt flares.i have hbvdna und so there is very little quantity of cells producing virus and alt flares will not happen

ntz+interferon is dynamite from what we have seen in our group and will fasten hbsag negative/hbsab positive much more than entecavir

it will be 3-6months not more

only if i find hbsag lower than 500iu/ml i will keep etv+ntz combo because this means hbsag is decreasing really very fast and it will be negative in a short time

[enolia]

Oh I see...That is very serious. You have to be very careful before going on Interferon. For me, keep using NTZ since it seems to work with no sides. You also want a quality of life and not worsen your Cirrhosis plus it is know that Interferon does not work too much on Hbe Neg so why take the risk!
As cajim said, Nutrition, rest, no toxins and also faith (I would say) help.
All the best.

[cajim]

Tell your friend to calm down.  At the Chinese site that I frequent patients like her are in the thousands.  They do what they can and life goes on.  From resistance to decompensated hepatitis there is still a long time and if she takes care of herself, it may never have to come.

Nutrition, rest, no toxins.

[stef2011]

never exposed to antiviral treatment so that probability of lam mutations is very low, but genome sequence is always required before starting therapy since lam, adv, mutations have been found also on patients never exposed to antivirals

for example i have natural mutations rtq215s/q, the rtq215s reduces responce to lam and adv and leads to immediate resistance.
i never started those n the past because i knew they were dangerous but if i started with lam now i would be complitely lost: no adv working, no etv working, reduced tnf and interferon with caution since on cirrhosis....correct choices of antivirals may make the difference between life and death as you can see from me, only ntz could have been ok at that point

[enolia]

Hi Stefano

What does "naive patient" mean?

[stef2011]

so my suggestion is:
tenofovir+ntz, no reistance issues and no sides (tenofovir has sides on less than 1% on kidneys)

[stef2011]

tenofovir resistance has been found in vitro but not in vivo, so only reduced results can be obtained on tenofovir.
the bad is she has been treated with wrong drugs, if it was 2000 only researchers knew LAM was the worst drug ever to use on hbv (there are about 5 to 10 mutations possible under lam that will reduce efficacy of other drugs), so this was the main mistake.
after 2004-2005 it was well know that lam was dangerous and not a cure and also the fact that entecavir doesn't work on LAM resistant is well known and that tenofovir is the only one working in this case.so your friend should have start with tenofovir from the begining as guidelines say now

luckily at the end of all this mess on 2008/2009 guidelines only tenofovir can be used as first line therapy and entecavir only in naive patients.

as regards your friend:
ntz, makes no resistance, active against all resistance mutated hbv strains, it can work as monotherapy on hbe negative, hbeab positive, low hbvdna faster than the other drugs

tenofovir, no resistance detected in vivo, active against all resistance mutated hbv strains

interferon. makes no resistance, active against all resistance mutated hbv strains, can have heavy sides, it doesn't work on high hbvdna loads

[chanthou]

Thank you both.  She is nervous because she has experienced with 2 drugs already and seem not working.  Not sure about the third drug (tenofovir or else). If the third one fails again, will this the end of her day? No more drug to rescue?

If she stops, there will be a flare.  That is why she is not happy now.

[cajim]

1.  Many users of LAM develop resistance, many doctors will prescribe some combo treatment to lower HBVDNA.

2.  Even when HBVDNA is brought to UND it does not mean there is no more virus or there is no more liver damage.

3.  Another direction to look to is to be liver-friendly and help make the body environment good for the liver and non-fitting for the virus.  For a long time, one may co-live with the virus but eventually the body gets healthier and the virus dies out.

4.  How?
a.  make sure the liver gets enough nutrition it needs;
b.  make sure you take in as little as toxins to hurt the liver;
c.  learn the new philosophy that as long as you are able to take care so that you eat well, sleep well, work well, live well, co-exist with the virus and live your natural live span, you have won the battle against the virus.
d.  also learn to be patient and learn not to be so thrown around by lab results because there are many patients with beautiful drug-controlled lab results yet they feel very sick; and there are some patients who concentrate on living right and feel great.

[stef2011]

LDN
my god it is for sclerosis or something with heavy sides?
no way there is no reason for this drug since tnf and ntz are practically free of drugs (maybe tnf some sides on the long period).
LDN is like making experiments i'd definitely go for well known safe drugs already proven safe and on guidelines, tnf 10 years on hiv and about 3-4years on hbv, ntz more than 10 years on millions of aids and babies diarrea

[stef2011]

follow my instructions and search this hbv community for alinia and you will find all the links to info
i ve upload some docs here:

https://docs.google.com/leaf?id=0B_yFgxI8KNcRNmI5YzEwMjgtNWU4MC00ZmYzLTlhNDItZTdiMjdmZTdiOGZj&hl=en

https://docs.google.com/leaf?id=0B_yFgxI8KNcRODEwMTJmNzgtYWMyYS00MDBjLTg3YTEtZTQ5ODQ5ODM5NWYw&hl=en

https://docs.google.com/leaf?id=0B_yFgxI8KNcRYWRhNzg4YTMtMjM5ZC00YmJiLWE3N2ItMTI4MThmYmM3MzU0&hl=en

https://docs.google.com/fileview?id=0B_yFgxI8KNcRNGIyZjk5YzktYTM0Ny00NTg1LThlZWUtNjc1ZGVhMzUzZGVl&hl=en

https://docs.google.com/fileview?id=0B_yFgxI8KNcRNzhhYjcwZTctMGJmOC00MjQ4LWI4ODAtOTlkM2EzNjdlMGVh&hl=en

Low Dose Nextralsone, never heard and nothing on google, do not use it, it is not on guidelines, plus do not trust the doctors have made this incredible mess they are killers not doctors

guidelines says to use tenofovir, unfortunately she has no drugs left but tnf or interferon, all the biggestes mistakes possible have been made on her and there is very little to do

alinia (nitazoxanide) will not be developped for hbv, there is no money from romark for hbv trials, plus there is no pay back from expensive trials since generics are already around in all third world and western countries (it is mainly produced in 3rd world because diarrea viruses are a big iusse there).

plus replicor has a definitive drug on hbv phase II so all companies stopped all hbv trial in 2009, no new drugs will be developped for hbv since there is no payback because of replicor compound, but it will take years for replicor to market new drug

she might also try interferon+ntz but interferon has heavy sides, i'll leave it as last rescue option (same as romark hcv trials, we have hbv people in our group on this combo and it is more potent than nucs)

[chanthou]

Thanks for your information.  Nitazonaxide is not known in my country and it is not prescribed for hepb. Is this drug on trial or generally used?  I saw on Hepatitis B Foundation it is under clinical trial Phase 2 in Egypt (?).

Can you provide more information about this drug in relation to HepB? Some suggest to use Low Dose Nextralsone (LDN).

[stef2011]

forgot to say hbvdna must be undetactable while on antivirals and baraclude doesn't work with lam resistance strains, the doctor made a big mistake i sue him immediately because guidelines are clear about it, only tenofovir can suppress lam resistance without new resistance mutations

i'd keep baraclude+tenofovir+nitazoxanide and stop baraclude when hbvdna gets undetactable if she stops baraclude all of a sudden she might have high hbvdna flares

please do find a good and expert liver specialist and consider that nitazoxanide is not known by most of the doctors and there is a higer rate of hbsag clearance of all other hbv drugs

[stef2011]

if i were you i'd make serious problem to the stupid doctor who made this mess, squential monotherapy worsen hbv disease this is a fact now

of course she is now resistant and only tenofovir might block hbv now, so first of all she must start nitazoxanide (alinia) and tenofovir immediately, because the more hbvdna gets high the less tenofvoir and ntz can work

ntz is active for all form of resistant hbv and activity has been measured for LAM resistant and adefovir resistant strains in particular.if she is hbeag negative and hbeab positive the responce to ntz will be strong and immediate.ntz makes no resistant hbv so she will have no trouble if she reaches und

she can also make a genome check of hbvdna to know all the types of mutations but this is not absolutely necessary because she has now no other therapies but tnf and ntz available

please make her start both as soon as possible because she is now in the most dangerous situation she might ever face, if hbvdna gets very high it might be a very bad problem

ntz must be taken with food (brakfast and dinner) 1pill 500mg X 2 Xday or higher dose 2pills 500mg X 2 X day.the only side can be diarrea because ntz can also kill bacteria and so healthy stomach bacteria too and make mild diarrea so she can take probiotics to prevent this like when you take antibiotics.
i'd start with low dose and rise to the higher dose if she has no diarrea problems

i really hope she is hbe neg so ntz will work very fast, tenofovir sould also be fast if she has not developped lam mutations that reduces tnf responce