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New findings from Professor Antonio Bertoletti

Earlier treatment for young patients with chronic hepatitis B more effective in clearing virus.

Link : http://medicalxpress.com/news/2012-09-earlier-treatment-young-patients-chronic.html
22 Responses
Avatar universal
The whole paper is available only  by paying a fee, so I have not read the whole paper. However, there is an editorial comment on the paper. It is a must to read. My interpretation is that the scientists have to revisit their research concerning suppression of our immune functions due to the virus. It seems we have to look at the micro environment insider the liver. This also raises questions regarding the role of excessive antigens in the suppression of immune functions. I hope I am wrong.
Avatar universal
That is a given, early treatment = better success. With any disease is like that..

What is bothering though is the attitude of these doctors (The whole paper is available only  by paying a fee) That is why we don't have a cure available for HepB yet..

Problem is finding an honest and genuine doctor these days..
Avatar universal
Treating young means treating during the immune tolerant phase when viral load is high, but ALT is normal. All guidelines recommend no treatment during this phase. Also the paper makes no mention of how to treat.
Avatar universal
this can be a changing point in the optic of treatment for HBV, but i think that this has to be confirmed by some other study before changing the way.
Avatar universal
makes sense but the present treatments are not very effective.  antivirals won't cure or make you seroconvert to antihbs.  

Interferon repsonse is 10-30%.  
Avatar universal
Interferon is weak and cannot really clear large hbsag loads.  Some people with low hbsag load still do not respond.  I suppose the guidelines only treat when there is more to gain.  like preventing cirrhosis.  Interferon injection therapy is not easy.    

also antivirals get incorperated into your liver cell DNA.
Avatar universal
BACKGROUND & AIMS: Chronic hepatitis B (CHB) infection acquired perinatally or in early childhood has been associated with a prolonged phase of immune tolerance from viral exposure into early adulthood. The immunetolerant phase of the disease is characterized by high levels
of hepatitis B virus (HBV) DNA and normal liver biochemistry, with minimal or no fibrosis. We investigated whether the age of patients with CHB affects their antiviral immunity and whether children and young adults have a veritable state of immunologic tolerance.

METHODS: We isolated T cells from different age groups of patients with CHB and used flow cytometric methods tomeasure production of effector and inflammatory cytokines (interferon, tumor necrosis factor, interleukin [IL]- 17A, IL-22, and IL-8), T-helper (Th)2 cytokines (IL-10, IL-4), Th1 cytokines (IL-2 and IL-21), and the CC chemokine CCL3 (MIP-1). We also measured markers of T-cell exhaustion or inhibition (PD-1, LAG-3, TIM3, LAIR-1, and CTLA-4) and HBV-specific T cells.

RESULTS: Young patients with CHB have a Th1-cell cytokine profile and a partial profile of T-cell exhaustion. Direct quantification of the HBV-specific T-cell response showed that young
patients with CHB have more HBV-specific T cells with the ability to proliferate and produce cytokines than adult patients with CHB.

CONCLUSIONS: HBV infection in younger patients is not associated with an immune
profile of T-cell tolerance. On the contrary, children and young adults with chronic HBV infection have an HBV-specific immune profile that is less compromised than that observed in older patients.
Avatar universal
They are beating the dead bush here. All this is known already.

What they need to be doing is treating people with everything that is available on much larger scale.
Avatar universal

i still have to read but the first thing i think is:

we do know since decades....hbv escpe immune response many times and mutates so much as we grow older, in youth immune system is more active and intf has higher response

drug makers need to drive attention off hbsag
Avatar universal

nothing new from abstract, what is said there is obvious and know already, almost ridiculous

the point is immune tollerant phase does not respond to intf because hbsag is too high and hbv is able to suppress intf, a combo intf+tdf+myrcludex may help or intf+rep9ac+tdf but wht we have available today doens t work to clear hbv!
intf+lam has been tried on immune tollerant young patients and response was higher than adults so maybe more trials are needed with intf+tdf
Avatar universal
nevertheless they should try those combos already today on more people. Interferon plus tenofovir is a good choice. But in my situation where i live it is impossible to try or find a doctor that will do it.

All I am saying is that these world  famous hepatologists need to stop recycling information at conferences and  open the doors in their clinics and actually treat people for not insane amount of money. Treat people on the larger scale.

Of course in those that immune system does not see the virus it will be tougher to get rid of it. If surface antigen is high and is deactivating interferon injections something like Gs 9620 will for sure bring it down to the point where immune system may wake up and will wake up in most  people.

But that we needed combo therapy they knew years ago.
Avatar universal
An important conclusion fro this paper is that "it might be better to start treatment early as young people with their stronger immune system, respond better to treatment and are more able to clear the virus." However, there are other equally important conclusions.

This is the comment from two scientists:

"In conclusion, the interesting study by Kennedy et al details two important, view-changing observations concerning tolerance during CHB. First, there is no inherent age-associated induction of tolerance in children and young adults with CHB. Second, where HBV-specific T-cell response were not previously thought to exist, such responses do exist, and were consistently observed through repeated follow-up analyses. Even the breadth of viral antigens targeted by HBV-specific T cells during the tolerant phase of CHB was surprisingly broad, and counters the prevailing opinion that immune recognition of HBV is somehow completely averted in certain individuals."
Avatar universal
good afternoon step.  can i ask question if u dont mind. for now do u have any recomend new products from the market to cure this hbv. how about ur latest studies. a lot people have hbv waiting for this. thanks for ur answer... godless us
Avatar universal
I like the idea where HBV evades our immune system by producing large amounts of hbsag which eliminates all our antibodies.  

This is evident by the fact that:

Replicor which suppresses hbsag release quickly allows most patient to produce antihbs.  

HBV does not cause generalised immune depression.  Most HBVers have normal immunity against everything else.  You do not usually see AIDS defining illness (eg cerebral toxoplasmois, CMV colitis, Candida oesophagitis) in HBV.  

However, i do realise we should all get rid of it as early as possible. Once the entry inhibitors and replicor comes out, we should all try and eradicate the virus.  

Death to HBV.

Avatar universal
Unfortunately, I don't have any new ones - all the latest ones are already discussed here. For me, the most hopeful ones are:
1. REP 9AC. This drug is based on the assumption that excessive s-antigen suppresses an effective immune response. Results from small clinical trials seemed to support this view. However, I have read a paper that cast doubt on this assumption. So only a large clinical trial will resolve this issue.

2. Use of potent antivirals to suppress hbvdna to undetectable for several years, then stop to elicit a flare or add IFN. This strategy assumes that long period of suppressed hbvdna level can restore effectiveness of our exhausted immune response. This should be tested again with large clinical trials.

On a longer term:

1. Myrcludex  added to existing treatments - this assumes Myrcludex will substantially reduce re-infection and hence accelerate loss of cccDNA?

2. IFN-lambda.

3. GS9620 - a persistent way to obtain IFN without injection.

4. Drugs to inhibit capsid formation, thus providing an alternative to existing NUC in case of drug resistance.

5. RNAi - hopefully this technology has matured and can also be safe.
Avatar universal
they knew all this years ago. That it is the immune system that needs to be rescued, that it is the key factor in overcoming/containing hbv.
Treating HepB before was less of a problem. For instance I will recap how HepB was treated in Russia in USSR - from what  I was told by people that were treating it back then.
As people developed symptoms during acute infetion they put them in the hospital usually 30-40day, start IV, and inject with vitamins it was heavy on D and A vitamins so I am told.. And also start interferon injection in those that had a weak immune response to the virus. That was 1970s and 80s. Where they were pretty much had to deal with it in the blind. There was some form of understanding about HBV. Why injection vitamins and iv fluids? They saw that many people had dysbiosis which was linked to immune system suppression and as Steph2011 said oxydative stress.
Using this method there were very few chronics ever emerged. Most if not all people that were chronic did not seek medical help while experiencing symptoms. How is that for a cost effective and timely treatment..
Now that in Russia for the past 20 years they have adapted many western methodologies and passive hbv treatment, many, many more chronic HBV cases out there. And the old school guy tell no we told you so.  So that is why they are going in a different route with thisMyrcludex, back to interferon and away from these antivirals or using them on top of interferons fro a short time not longer then a year..

So there is nothing new what these so called world renoun researchers write that early treatment equals better is  a given and or that we need better drugs that lower surface antigen in chronic cases.
But They do have better drugs now btw.. GS9620, Rep9AC. Imiquimod btw as far as sic years back was suggested to be used for HCV for its antiviral effect. So they are well aware of what works..
Why should it take half a decade or a decade to approve these? They worry about safety? Really? Don't they worry about HCC that we are facing, or long term side effects from taking antivirals that really are not well suited for hbv since they have very little effect on the surface antigen in the first place. Multiple articles linking Baraclude to Cancer, Tenofovir to kidney damage. And yet it is full steam ahead with these drugs. Might as well put us on Truvada, that is optimised to safety concerns in terms of dosing, and forget about resistance period. That is another issue that they were warning about these drugs. But I think we are heading this way to Truvada, for those that will fail or become drug resistant to all the drugs.
But, Interferon was the best choice for us in the 70, 80's 90's and today.. yet it is not most often used in the western countries.

These guys the likes of Bertoletti should use these drugs today like GS9620, Rep9AC, Myrcludex rather then writing theories and making small trials sponsored by the drug companies and calling it research.
If you watch HBV development over the past five years the progress is very slow if any. But we have options. The studies of Herbal and other supplements that have been reported in traditional medicine are vertually none existant. But they can offer some support to existing therapy. Look at Heptech that Stef2011 takes and how it helped him. This is what I call research, not just obseravtion study of how I like my Baraclude.
If anybody is doing research it is patients like Steph2011 on these forum. People who go further  then most hepatologist will ever go these day by trying the stuff that is available today. And that is just one committed individual. And not a doctor or researcher that spend years in study.
They are taking a totally wrong approach about eradicating chronic hbv. They are giving us antivirals while drug companies like Gilead sit on cures so they can profit more from Tenofovir sales.
And it is ultimately comes down to us folks how active we will be. Sure we need a strong advocacy group to change the way new treatment are introduced directly to the patient, and the amount of time clinical trials take place. There is absolutely no reason why a clinical trial of anti HBV agents cannot be completed within a year. stages 1, 2, and 3.. given the grave consequences chronic active hbv infection does. That is what should be discussed at the liver conferences.
Tenofovir and Entecavir are not safe drugs by any means, the solid safety data is out there for about 3 years on them direct use without concequnces....all the negative data is being reported on nucs on HIV forums about these meds. And yet they are the first choice now of many doctors as the first line of treatment. Judge by this forum. What are the newbies get recommended first with no liver damage, elevated ALT and low viral load? Viread.. when in fact Pegasys or any other interferon is the way to go for them. And their doctor should know that. Yet most hepatologists I have seen would go into arguement against using interferon advocation only the use of an antiviral. And then you look at his office or a clinic and can't help but notice very heavy Gilead presence in terms of marketing literature. And that is where lies the real problem with this.

Adding an antiviral on top of interferon is a good thing - but that at least in the US is considered a rocket science! But do you buy that? Statements like that US is years behind in HBV research? if you compare it to say what DARPA is doing and the projects they work? They got the best dogs on their science teams. That sure could work on HBV or HIV and Cancer and they would go further and faster then say BMS or Gilead. That probably buy off this research from smaller companies if it is promising.
CHB infection is all industry now damnit. And we have to wait another 5-10 years. How many will make it there?
In all their animal studies, and preclinical trials companies like Gilead are well aware what they are putting funds into.

All this info of course is a good for the new guys to educate them about what they are dealing with. But for someone that has been on this bus for six or 10 is interested in real changes where these drug companies start thinking more about the patients life. And these researchers too,  a good start would be not to charge money for someone to read the article :)
Avatar universal
If I were to treat all adults that show symptoms of hepatitis with water, I will get an over 90% cure rate, i.e. they will not become chronic. Of course, those with no symptoms, they will not become chronic because they will not even know  they were infected.
Avatar universal
The question is would you treat inactive carriers. since they are young and supposely got better cytotoxic cells.  They already killed the wild type but cannot overcome hbsag due to cccdna.  So they may remain inactive until they clear hbsag spontaneously or a mutant develops.  shouldn't you let sleeping dogs lie.  

I think one should try to treat immuntolerant phase.  although, the drugs we have now may not work.  
Avatar universal
LOL :)

I agree.
Avatar universal

i agree and they already did even worst with some drugs...curing the healthy ones with invented diseases....only information sharing like medhelp can stop these institutional hidden frauds

by the way do you remember the research at easl showing 30% clearance on inactive carriers with hbvdna und...i think only nucs are generally pushed just to make money while all other treatments are available only by good doctors, researchers or very informed patients

Avatar universal
Boy health insurance companies would live you. You would save a lot of money for them.:)

Here is one point you are missing. Those with very weak immune response tohbv (no symptoms) according to Russian doctors had the higher chance of becoming chronic carriers. That is why they were given them interferon from the get go. To avoid formation if mutants during immune clearance phase. Because chronic hbv is as you know tough to treat..

Now they provide no treatment to acute cases in those that seek medical help and the there is more chronic cases. Way more. And that is a fact that in some cases such as mine hbv really cripples immune system and one is not able to clear it. Why that happens in some individuals and not in others  no one is yet sure. But what i am saying even as far as 20 years back they  knew something that is being reaffirmed today in these research papers.

Early treatment is of course makes sense while the immune system sees and has some control of the virus.  
Avatar universal
Health insurance companies dont like interferon be prescribed at least here  not to have possibly pay for the hospital stay of the patient do to complications.

Good and honest doctors i dont know where to find those. I know  it sounds insane to say but out of  50 or  maybe as high as 100 people i saw nothing but the feeling of frustration   i felt leaving their office. The only thing they do good is charge money. And that is University level doctors here. Private practise people just have no clue what to with hbv.

I really dont know how much money one needs here in states to see people that would treat the way we are discussing here.

It is either tenofovir or baraclude they start out with. And you can tell sometime which drug it would be based on the marketing literature in their office.

Prescribing nucs is easy , and cheaper for the health system so that is why.

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