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Entecavir + Interferon combo
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Entecavir + Interferon combo

Dear all,

     I have been on Entecavir 0.5mg for over 6 years and my HBV DNA is nearly undetectable.  I will see my doctor tomorrow and what tests should I perform so as to assess whether I will benefit from the Entecavir + Interferon combo treatment (i.e. higher chance to achieve Hbsag seroconversion.)  Many thanks.

Regards,

Cyrus
127 Comments Post a Comment
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Avatar_m_tn
6 years of usage but not Undetectable? I thought you have to be undetected in 6 months. Do you mind sharing your latest lab result starting with HbsAg (iu/ml), HbeAg -/+, HBV DNA and Fibroscan?
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Avatar_m_tn
Yes still detectable, last HBV DNA was about 180 copies /ml.  I am HbeAg+ and have not tested for HbsAg quantity.  Fibroscan done a month ago and will see my result tomorrow.
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Avatar_m_tn

detactable hbvdna after 6-12 months is failure of the antviral and add on of tenofovir or tenofovir switch is needed.i hope hbsag lowered even if hbvdna was detactable

if you add intf you can keep etv and see results of this combo, please let us know after 6years intf should work on hbsag
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Avatar_m_tn
Should I do some tests e.g. hbsag quantity, hbv genotype etc. to assess my successful rate before I start etv + intf combo?
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Avatar_m_tn
Yes, I also thought etv is not effective for me but my doctor (as my previous post mentioned) advised me to use entecavir 1mg instead of adding on tdf.  I will see him again tomorrow and don't know what to do.
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Avatar_m_tn

no increasing etv dose is useless, 1mg has even less potency than 0.5mg on latest reports and doesn t work to prevent resistance, it really makes no sense
best option is 6months of combo etv+tdf, if hbvdna becomes totally und etv can be discontinued

unless your doctor has benefits from the drug maker to prescribe etv what he says makes no sense, tdf is more potent, no resistance, cheaper and same effect on kidneys function as etv

or you may try intf+etv 1mg, intf should work on the partial response of etv and little hbvdna detactable might stimulate intf response more

yes make tests to check for resistance mutations, genotype, hbsag quantity, whatever the results i d try intf anyway unless we find a very high hbsag up to 10.000-20.000iu/ml
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Avatar_m_tn
Just want to mention some latest research findings:
1. The rate of HBeAg seroconversion using antivirals is lower in real practice than those reported in clinical trial
2.  Intensifying entecavir (Baraclude) treatment for hepatitis B by adding pegylated interferon lowers HBV viral load and increases the likelihood of hepatitis B "e" antigen (HBeAg) loss, according to a report at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2012) last month in Boston. A related study found that hepatitis B surface antigen (HBsAg) levels during treatment can be used to predict response to interferon.

Nucleoside/nucleotideanalog antivirals that interfere with the hepatitis B virus (HBV) lifecycle are standard treatment for chronic hepatitis B. They perform well for lowering HBV DNA levels, but serological response, including HBeAg and HBsAg loss or seroconversion, occurs in only a minority of patients.

Interferon -- long the mainstay of hepatitis C treatment -- stimulates the natural immune response against viral infections and may contribute to improved outcomes for hepatitis B as well.

Milan Sonneveld from Erasmus University Medical Center in Rotterdam and the ARES study team conducted a controlled trial that enrolled 184 HBeAg positive patients with compensated liver disease at 15 sites in Europe and China. About 60% were of Asian ethnicity and all major HBV genotypes were represented.

One group was randomly assigned to take 0.5 mg/day entecavir monotherapy for 48 weeks; the other group received the same dose of entecavir, but after 24 weeks of monotherapy they added 180 mcg/week pegylated interferon alfa-2a (Pegasys) and continued on triple therapy through week 48.

Results

    74% of participants in the entecavir monotherapy group and 83% in the interferon add-on group achieved HBV DNA < 200 IU/mL, but the difference did not reach statistical significance
    53% and 61%, respectively, reached HBV viral load < 20 IU/mL, again not a significant difference.
    8% of patients the entecavir-only group and 18% in the add-on group experienced HBeAg loss, which just missed being significant (P=0.068).
    In a multivariate analysis, the only factors independently associated with combined response were:

o   HBsAg level at baseline: odds ratio 0.42, indicating that a lower level raised the likelihood of response;

o   Addition of pegylated interferon: odds ratio 3.78, or nearly quadruple the likelihood of response.

    Adding pegylated interferon to entecavir was generally safe and well-tolerated.
    5 people experienced serious adverse events, including 3 ALT flares during the entecavir monotherapy phase.
    Neutropenia (0% vs 23%) and thrombocytopenia (0% vs 8%) were significantly more common in the add-on group compared with the monotherapy group; no one in either arm developed anemia.
    2 people developed severe neutropenia while on pegylated interferon.

"Addition of pegylated interferon alfa-2a to entecavir monotherapy increases HBV DNA, HBeAg, and HBsAg decline," the reseachers concluded. "Addition of pegylated interferon alfa-2a to potent [nucleoside/nucleotide] analogue therapy may increase chances of finite therapy."
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Avatar_m_tn
Thanks Stefano for your prompt advice.  I am a bit afraid of the heavy side effects of interferon.  
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Avatar_m_tn
How about side effects after a liver transplant not afraid of those? You have e antigen positive hbv. Why they were treating you with nucs then interferon was the rightvway tovgo about it. These doctors who prescribe anti aids drugs to us kill us really. Speak with honest docs they will tell you
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Avatar_m_tn
With this study result, should I still try interferon?

Entecavir and interferon-α sequential therapy in Japanese patients with hepatitis B e antigen-positive chronic hepatitis B.
Enomoto M, Nishiguchi S, Tamori A, Kobayashi S, Sakaguchi H, Shiomi S, Kim SR, Enomoto H, Saito M, Imanishi H, Kawada N.
Source
Department of Hepatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.

Abstract
BACKGROUND:
The outcomes of sequential therapy with lamivudine followed by interferon have been unsatisfactory in Japanese patients with hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B. However, the efficacy of sequential therapy with entecavir and interferon remains unclear.
METHODS:
Twenty-four HBeAg-positive patients (23 men and 1 woman; mean age 39 ± 7 years) received entecavir 0.5 mg alone for 36-52 weeks, followed by entecavir plus interferon-α for 4 weeks, and lastly by interferon-α alone for 20 weeks. Twenty-three patients had genotype C infection, and one had genotype A infection.
RESULTS:
No entecavir-resistant mutant variants emerged in any patient. Hepatitis flare occurred in three patients during interferon-α treatment after the withdrawal of entecavir, but none had hepatic decompensation. Serum hepatitis B surface antigen levels did not change during or after therapy. Serum hepatitis B core-related antigen levels were significantly decreased at the start (P < 0.0001) and at the end of interferon-α treatment (P < 0.0001), but returned to baseline levels after treatment. Twenty-four weeks after the completion of the sequential therapy, a sustained biochemical, virological, and serological response was achieved in 5 (21 %) patients. The proportion of patients in whom HBeAg was lost during entecavir treatment was significantly higher among those with a sustained response than among those with no response (P = 0.015).
CONCLUSIONS:
The rate of response to sequential therapy with entecavir and interferon-α in Japanese patients with HBeAg-positive chronic hepatitis B was not higher than the rate in previous studies of lamivudine followed by interferon.
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Avatar_m_tn
Any advice, please?
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Avatar_m_tn
No advice, just some opinions. As you can see from both studies, responses to ENT + PEGINFN combo vary. Of course, your situation is not typical of both studies. Firstly, I want to ensure that you have complied with your daily intake of ENT on an empty stomach. HK has some of the most experienced liver doctors in the world, so you have an advantage there. Finally, I would check your quantitative HBsAg level before deciding.
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Avatar_m_tn
Dear Stephen,

Thanks for your prompt advice / opinions.

I had been taking entecavir at 1700 hrs everyday (I would finish taking my lunch at 1400 hrs and would start my dinner after 1900 hrs).  A few months ago, I changed to take entecavir at 2300 hrs (just before sleep) and I would normally finish my dinner before 2030 hrs.  Is this routine ok for the empty stomach requirement?

Yes, I agree that Hong Kong has some of the most experienced liver doctors (as we have my Hep B carriers here).  But my doctor would like to prescribe entecavir 1mg and I don't want to take entecavir indefinitely (due to its carcinogenicity).  That's why I ask if my chance for ent + interferon combo.  I will definitely ask him to test my HBsAg quantity today.

Regards,

Cyrus
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Avatar_m_tn
Thanks for the info. Yes, most people ENT just before going to bed. As for carcinogenicity, I believe there is on-going monitoring of this since ENT was approved by FDA because ENT tested positive in for carcinogenicity in an animal study. So far, FDA has not issued any warning nor made changes to the label information.
Still 180 copies/ml, i.e. 33 iu/ml, is a very very low number, below the "detectable limit" of many assays. Some research indicated INTFN can reduce level of HBeAg (as well as HBsAg), so it should help with your seroconversion, whether it is desirable to have the e-Antigen seroconversion is not clear to me.
Just my opinions.
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Avatar_m_tn
Today I met my doctor and get my latest result:

Fibroscan : 4.2kPa
HBV DNA : undetectable

He advised me to continue 0.5mg entecavir monotherapy as I am still HBeAg+ as he predicted that my outcome using ent + intf combo will be the same as the ent mono.  I did request to test for HBsAg quantity and will discuss with my doctor again when I know my baseline HBsAg to see if it is worthwhile to add intf.

Thank you all for sparing your time in giving me valuable opinions.
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Avatar_m_tn
Dear Stephen,

      May I know that if my HBV DNA is now undetectable, will it rebound soon or later?  Many thanks.

Regards

Cyrus
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Avatar_m_tn
I am sure it will not rebound soon, but in the future, I would say no too. Of course, it is just my opinion. So far, research indicates response to Entecavir continues to be durable, that is, if you keep on taking Entecavir, you keep getting response. It seems your liver is in good condition (4.2Kp), hbvdna undetectable and I bet your ALT is also normal. So what can you expect in the future? I think, after you seroconvert your e-antigen, after a further 12 month consolidation, you may consider stopping all treatment and see whether your immune system can maintain control on its own. This seems to the view favored by researchers in Taiwan. Or you may consider combination with Peg INFN with the view to aim at clearing your HBsAg. Or you may just continue Entecavir until you seroconvert your s-antigen too.
So I think you are in a very good position, your HBsAg level may give you a better prediction of what is going to happen next.
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Avatar_m_tn
Dear Stephen,

Thanks a lot for your response.

Regards,

Cyrus
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Avatar_m_tn
Dear Stefano and Stephen,

Thanks a lot for your valuable advice before.  I just got my HBsAg quantitative result which is 456 IU/ml.

With this result, should I start interferon and what is the estimated chance of a  complete cure?

Many thanks.

Regards,

Cyrus
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Avatar_m_tn
HBsAg of 456 iu/ml is a very good number. If you were HBeAg negative, you would be considered "inactive". It is certainly favorable to clearance by PegIFN treatment. I cannot give you an estimate. You may like to consult your doctor or seek an opinion from one of the experts.

In a recent study in China, 16 HBeAg negative inactive carriers with HBsAg < 200 iu/ml received PegIFN treatment and all of them cleared their HBsAg. Your situation is different as you are on antiviral treatment and still HBeAg positive. However there are studies that indicate PegIFN is more effective for HBeAg positive patients than HBeAg negative.
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Avatar_m_tn
immediately start peginterferon with entecavir add on and ezetimibe add on, chance to clear is highest and you may clear in just 24 to 48weeks

see otan results, she/he had about same hbsag level and cleared hbsag in just about 16weeks
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Avatar_m_tn
My ALT are normal  SGPT  35  limit is 15-72
                             SGOT  38  limit is  20-52

HBsag =Reactive
HBeag= Non Reactive
Anti-Hbeag= Possitive.

Is i am inactive and is there any cure for this
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Avatar_m_tn
your alt are not normal, those ranges are so obsolete alt range has been updated few years ago to alt less than 30 for men and less than 19 for women

to know if you are inactive you need fibroscan less than 6kpa, hbsag quantity in iu/ml less than 1000iu/ml genotype A and D, less than 100iu/ml C and B (not sure about b and c so i ve used a very low level) and hbvdna quantity in iu/ml less than 2000iu/ml

even your alt are not normal so you are not an inactive carrier at all, your doctors may be very very ingnorant on hbv and not updated on the diseases since years better change doctors
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Avatar_m_tn
Recently i have done the alpha feto protein AFP 2.91 ng/ml Reference range is upto 20 ng/mL is this within range.

My doctor told me as ALTs are within range no need to do the HBV DNA and no need to take medicine is it write.
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Avatar_m_tn
afp is useless as marker of HCC, it stays normal in most of HCC cases and gets high with alt flares inflammation....just a mess, US every 6 months is the best way for monitoring HCC prevention

My doctor told me as ALTs are within range no need to do the HBV DNA and no need to take medicine is it write.

change doctor this is from prehistory and not updated on personalized hbv cure at all, if he is not able to manage an easy patient like you who can clear hbv he is just selling drugs to the chronic carriers...i d call him seller and not doctor.since i met such doctors myself too and they made me a lot of damage today i dont even consider them doctors and just want the best doctors/researchers

etv may clear your hbv in a very long time or hbv may mutate hbsag/hbcag and escape your immune response now, you better use peginterferon add on and stop it now, when you look for another doctor just ask for "expert liver specialist updated with latest personalized hbv therapy which is made by combo antivirals plus peginterferon"
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Avatar_m_tn
as said in previous post your alt is not normal both the lab you use and your doctor are 2-3years not updated about hbv, this is not tollerable becuase everything can change from year to year in the "cure of hbv" not just managment
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Avatar_m_tn
peginterferon plus antivirals is used since 2004-2005 so this is nothing knew, today we know it allows hbv clearance on low hbsag carriers
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Avatar_m_tn
Your ALT is mildly elevated by the new standards. To be certain you do not require treatment at this stage, you should measure your viral load(hbvdna). Hep B is a chronic disease and can be tricky. You should not rely on just one test, or test results at a single time point.
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Avatar_m_tn
Dear Stefano,

Could I just use Interferon + entecavir combo or ezetimibe must be added on?

Btw, I notice from my blood test report that the HBsAg quantitative measure was done 1 month after my blood was drawn.  Will this affect the test accuracy?  Many thanks.

Regards,

Cyrus
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Avatar_m_tn
Dear studyforhope,

Any suggestion from you about my case, please?

Many thanks.

Regards,

Cyrus
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Avatar_m_tn
You are und now on entecavir, but it was pos for 6 years, it might be smart to switch to tenofovir.

If you start ent plus interferon now, you do have a small chance to clear the surface antigen. Better, much better than patients with a higher hbsag, but still small, maybe 30% if limited to one year, getting a little higher with extended treatment. But the side effects are not trivial, so it is a somewhat difficult decision.

Ezetimibe is a fascinating add on, but we need to see first how stefanos surface antigen will further develop with this treatment. There is a first hint of an effect, but we need to see more.
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Avatar_m_tn
Dear studyforhope,

Could you please further elaborate why it would be smart to switch to tenofovir?

Many thanks.

Regards,

Cyrus
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Avatar_m_tn
Your response to entecavir was suboptimal since it took you 6 years to reach an uncertain undetectable status. Entecavir resistance can start with mild partial resistance mutations.

While it might not ever progress any further, tenofovir is very available and even much less prone to any  resistance.

Furthermore tenofovir is an obligate chain terminator and will never be incorporated in mitochondrial or any DNA, since it is lacking the connecting hydroxyl group. Entecavir however can rarely be incorporated into the growing DNA chain, this feature might be the reason for the high cancer incidence in the animal studies as Stephen mentioned. Thus far it does not seem to be a major concern in humans, the FDA has requested a long term study on this from BMS, no red flags seem to have surfaced yet.
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Avatar_m_tn
Dear studyforhope,

Thanks for your kind advice.

In case I need to switch to tenofovir, should I first keep taking entecavir concurrently for six months before stopping it as previously advised by Stefano.

Provided I can tolerate the side effects (I am now 39 y.o. with 4.2KPa fibroscan result last December and recent ALT of 25), do you think it is worthwhile for me to start interferon treatment with my HBsAg = 456 IU/ml?

So in what range of the HBsAg level will have a higher chance of clearing HBV?

Many thanks.

Regards,

Cyrus
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Avatar_m_tn
One week of  overlap will be sufficient if you switch to tenofovir.

With your sag level a trial of add on ifn is meaningful. More detailled predictions cannot be made.
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Avatar_m_tn
You say find a doctor that has an up to date knowledge on treating hbv. I have seen maybe 50 people already over 7 year period and they have no clue what they are doing. Just following treatment guide line they were given. And that is it.

It is really a frustrating feeling. But nothing but nucs is available here. :(  and when you try to reason with these so called doctors they get upset and leave. That is what we have to deal with.  

I am open to go to any country they take me for real treatment. And I am sure people are. But  it really ***** how they treat us here for the amount of money we pay. We pay more then you Europeans. Docs hers minimum make 150k that is just primary care internal medicine docs. It is unbelievable how bad things are regarding hbv care and attitude of these so called doctors. Bunch if greedy snobs that only care about money.  
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Avatar_m_tn
Dear Stefano and studyforhope,

I will soon discuss with my doctor whether I should start the combo i.e. adding interferon on top of my existing entecavir treatment.  He seems unconvinced that interferon will work on my case and so if you have any research papers to share, I could show him for further discussion.  Many thanks.

Regards,

Cyrus
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Avatar_m_tn
There are almost no publications on this combo at this time.
The results are only good when the starting hbsag quant is very low and the dna is und.

Here is an example of a nuc first then ifn  add on therapy trial.

J Clin Virol. 2012 May;54(1):93-5. doi: 10.1016/j.jcv.2012.01.024. Epub 2012 Feb 24.
Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B.
Kittner JM, Sprinzl MF, Grambihler A, Weinmann A, Schattenberg JM, Galle PR, Schuchmann M.
Source
I. Medical Department, University Hospital Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Jens.kittner@unimedizin-mainz.de
Abstract
BACKGROUND:
Nucleos(t)ides effectively halt disease progression in hepatitis B but require long-term medication.
OBJECTIVES:
To determine whether add-on of peg-IFN to an ongoing nucleos(t)ide therapy accelerates decline of HBsAg and induces seroconversion.
STUDY DESIGN:
We observed HBsAg kinetics in 12 patients on a stable oral therapy with undetectable HBV-DNA who additionally received peg-IFN-alfa 2a as an individualized therapy. 3 patients were HBeAg positive. Mean baseline HBsAg was 4695 (range 16-15,120)IU/ml.
RESULTS:
A continuous decline of HBsAg was observed in 2 patients. The slope, respectively, became detectable at week 8 or 16. HBsAg had dropped by 2.90log(10) or 4.25log(10) fold at week 48, and anti-HBs appeared at week 40 or 32. Patient A - HBe-positive, genotype A, F3 fibrosis - had been HBV-DNA negative for 10 months receiving entecavir plus tenofovir. Previous therapy with peg-IFN had been unsuccessful, but now the patient experienced HBeAg seroconversion at week 24. Patient B - HBeAg negative, genotype D, cirrhosis - had a low initial HBsAg level of 16U/l. Receiving entecavir, his HBV-DNA had previously been non-detectable for 27 months. In the remaining 10 patients HBsAg declined only by a mean of 0.09log(10) (range 0.01-0.25log(10)) after 8-24 (mean 16.4) weeks, and therefore, peg-IFN was stopped. No unexpected side effects were observed.
DISCUSSION:
We observed that the add-on of peg-IFN induced HBsAg seroconversion in 2 out of 12 patients. Response rates may have been higher with prolongation of therapy. The add-on concept merits to be evaluated in a clinical trial
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Avatar_m_tn
Hi

Just wanted to tell you that you should not be that scared of IFN sides.
In my case its just being tired on afternoons just after shot and dehydration so I drink a lot of water. Besides that maybe I could say trouble with concentration but I'm not sure if its the IFN or the nerves with the disease.

I would try Interferon for sure. Week 12 or 24 you can check HBsAg again and check if you are responding so its not that long.
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Avatar_m_tn
Thanks a lot but the thing is whether my doctor is willing to start the interferon.  The other concern of mine is that I may not be able to go on a trip if the injection of interferon has to be done by medical practitioners.
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Avatar_m_tn
I understand.
The injections are very easy to do by yourself. The needle is maybe 2cm long and you do it in your abdomen (can also be leg but I prefer abdomen as there is more fat :) )
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Avatar_m_tn
Dear calebz,

Thanks but IFN is a prescribed medicine in Hong Kong and I think I could only get it from my doctor if he approves such treatment for me.  Btw, how is your result after IFN injection?

Regards,

Cyrus
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Avatar_m_tn
Not sure at this moment yet. I am on week 18 with injections.
My DNA keeps the dropping curve from 170000 IU/ml baseline to 3000 IU/ml on week 12, but my HBsAg is acting up baseline 4400 dropped to 3700 w4 and goes back up 4400 w8 and to 4700 w12.

Doc says we need to wait for W24 to see what is the pattern of it and then rethink my treatment.
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Avatar_m_tn
Dear calebz,

Good luck and hope you can achieve sustained response.

Regards,

Cyrus
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Avatar_m_tn
You asked for literature for your doctor. Here is the abstract that showed the best success rate. Note that all cleared patients had very low hbsag quant at start.


Improvement of HBsAg Loss by additional PEG IFN in Nucleosides Analogs treated Chronic Hepatitis B Patients
Zhongwen Wu, Jifang Sheng, Lanjuan Li; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases,the First Affiliated Hospital, College of Medi- cine, Zhejiang University, Hangzhou, China
Background and Aim: Suppression of HBV-viral load by nucleos(t)ide analogs(NAs) treatment reduces disease progres- sion but requires indefinite treatment. Hepatitis B surface anti- gen (HBsAg) loss or seroconversion is a rare event after long term treatment of NAs. PEG-IFN could induce sustained immune response and lead a significant decline of serum HBsAg., Our study aimed to explore whether NAs treated patients who have achieved sustained virological response (SVR, defined as HBV- DNA < 1000 copies/ml) and obvious decrease of HBsAg level, add on the treatment of peg interferon alpha-2a for 48 weeks could achieve high HBsAg declination and even got HBsAg loss. Methods: 32 chronic hepatitis B patients have received NAs for 1.5-4 years, 65% of the patients achieved HBeAg sero- conversion. all patients with HBV-DNA < 103 copies/ml, obvi- ous decrease of HBsAg level 100-500 IU/ml (using time-resolved immunofluorometric assay) were enrolled into the study and divided into two groups: GroupA with 16 patints (M/F: 14/2, median age 31years, 5 HBeAg positive,)
received additional peg-interferon alpha 2a (180ug/w) for 48 weeks; other 16 patients (M/F: 13/3, median age 34 years, 6 HBeAg positive) in Group B continued the NAs therapy for 48 weeks. Median baseline HBsAg was 209.64 IU/ml in Group A and 193.18 IU/ml in Group B. Results: In GroupA, eight out of 16 patients (50%) had a continuous HBsAg decline which lead to HBsAg loss (<0.5 IU/ml), HBsAg seroconversion was observed in five of them (31.3%) . Quantitative HBsAg highly decreased to below 10IU/ml in twelve patients (75%). Two out of 5 HBeAg positive patients had HBeAg seroconversion, 1 had HBeAg loss, In Group B, no significant HBsAg decline was observed at week 48, even fluctuated round to the baseline level, and none of six HBeAg patients in group B achieved HBeAg loss or seroconversion. Conclusions In chronic hepatitis B patients, with SVR and obvious decrease of HBsAg level after NAs treatment add on a finite course of peg interferon alpha- 2a treatment could significantly drop the HBsAg level (75%), even lead to HBsAg loss /seroconversion (50%) . This appears to be a promising approach for further investigation.
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Avatar_m_tn
Dear studyforhope,

Thanks a lot for your information.  Btw, I am also a bit concerned on whether the IFN add-on will lead to acute hepatitis.  Is this common?  Many thanks.

Regards,

Cyrus
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4853518_tn?1360053723
hi  gusy   im  hepa b  reactive,
  can  you  explaint Me what is this   my  reuslt
last  Feb 25 2013 (cov is .236  AB 2.420)

March 15 2013 the new   hepa screen. is
(cov .30 Ab 2.420)

have a improvement or not  plzzz  help Me guy
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4853518_tn?1360053723
hi  gusy   im  hepa b  reactive,
  can  you  explaint Me what is this   my  reuslt
last  Feb 25 2013 (cov is .236  AB 2.420)

March 15 2013 the new   hepa screen. is
(cov .30 Ab 2.420)

have a improvement or not  plzzz  help Me guy
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Avatar_m_tn
No at your surface antigen level, interferon will not lead to any substantial acute hepatitis. But is has severe side effects for some, others tolerate it pretty well.
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Avatar_m_tn
i've done 2 ifn course.. the last was 14 months.. no sides at all,.,
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Avatar_m_tn
Any change in qHbs after 2 courses? I am on my 28th week of Pegasys. Hbs goes up and down within 10% range. Baseline is 10 000 iu/ml. After 24th week no change in quantity of hbs my doctor suggests me 96 weeks of interferon instead of 48 weeks. So far no decline in qHbs. Some papers say if no decline on 24 weeks then useless to continue interferon but my doctor is of diffirent opinion.  
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Avatar_m_tn
no.. on 24 wks you shoud stop according to guidelines... anihow i kept on as my docs think ifn has an effect also after the therapy..
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Avatar_m_tn
Hi. I have similar experience - my hbsag is just fluctuating and I'm at week 18.
How is your DNA level and ALT during treatment?
I saw some chart where there is a small chance of SVR even if HBsAg doesn't decline so lets not give up.
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Avatar_m_tn
Did your liver condition improve durinig interferon treatment in terms of Metavir score? I mean did you do fibroscan before and during the treatment to monitor progress?
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Avatar_m_tn
My DNA went to undetectable but the baseline was 1000 iu/ml not high anyway. ALT was in the upper top but within normal level now somewhere inbetween,
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Avatar_m_tn
... so why have u been treated with sucha  low baseline??? are you EAG-ve?

I had last bioposy in 2007... it was close to Metavir score 1...
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Avatar_m_tn
because Hep b is not only about HBV DNA but qHbs to me. Being undetectable in viral low is so much depressing for me knowing I have many Hbs and the only possible medicine affecting hbs is interferon that's why i started tx. Perhaps getting undetectable with interferon gives more advantages then getting same with  NUCs, I do not know, I hope so.
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Avatar_m_tn
Dear all,

I will meet my doctor tomorrow to discuss with him whether I should add-on IFN to my ETV monotherapy.  While I the add-on treatment might give me a chance of getting rid of Hep B, but I am also concerned about whether the treatment may poise negative effects on my general health and also turning my chronic hepatitis into acute one.  Any comments are greatly appreciated.  Many thanks.

Regards,

Cyrus
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being under etv will make any possible alt flare a totally non issue, remember that even compensated cirrhotics can be treated by peg.i d definitely go in to etv+pegintf+simvastatin your levels of hbsag are the same as otan and she/he cleared by 16weeks on pegintf+sim

so you are in such a favourable status that hbsag may even be cleared before the first round of tests which is ususally at 12-24 weeks
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as to sides most have just like a flu which is not even to consider so bad, others have none...i mean with the possibility to clear hbsag so fast i d jump into peg immediately
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Dear Stefano,

Thanks a lot and I will talk to my doctor today.  Will keep you all posted.  

Regards,

Cyrus
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Dear Stefano and calebz,

I just had my first shot of IFN this morning and I developed fever (39 C by ear thermometer).  The fever subsided to 38 C after taking 1 pill of 500mg paracetamol.  Other than fever (and some flu-like symptoms) and high pulse rates (about 80 - 90 pulses per minute), I feel generally fine.

Just wanna ask how long will the fever last and will you continue your daily routines e.g. physical exercise?

Furthermore, mine IFN is packaged in pre-filled syringe and the nurse recommends me to place the syringe in room temperature for about 1 hour before injection.  Will this affect the effect of the IFN?  

Many thanks.

Regards,

Cyrus
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this fever usually happens only at first injections


the nurse recommends me to place the syringe in room temperature for about 1 hour before injection.  Will this affect the effect of the IFN?  

i guess not but i remember my family members did not left it so long,  small vial gets to room temp in few min
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Dear calebz,

Any experience you could kindly share?

Many thanks

Regards,

Cyrus
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I think I had 38 degrees but in my case its very hard to tell as when I had my first injection as I had a mild cold and I'm not sure if I should assign my 38 fever and cold sympthoms to the regular cold or to IFN. Nevertheless they went away within 3 days.
I didn't check my temperature that often as I felt pretty good in general. I think you need not to worry about temperature and stuff like that if you feel ok.
You know your organism best and just adjust to it - if you feel tired then rest/sleep. In my case even 20 minutes of rest/sleep works wonders on the afternoons.

Nobody told me about warming up the synergies before injection so I just take it out of the fridge and inject. I think if it was important they would label it properly but as stef said warming up this amount of liquid is a matter of minutes.

I know first injection is a little panic on whats gonna happen but try and drink a lot of water and heads up its gonna be less and less sides every injection.
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Dear calebz,

Thanks a lot.  Do you continue exercising while on IFN or reduce the intensity of your physical exercises after starting IFN treatment?

I recently started to suspect I have hypertension (blood pressure ranges from 120 to 140 / 75 to 85).  Is this contraindicating to IFN treatment?

Many thanks.

Regards,

Cyrus
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I did but stopped as stef suggested you shouldn't get tired when on interferon.
Only a 30 minute walk everyday and regular house activities.
High blood pressure starts 140+.
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Dear calebz,

Thanks for your prompt reply.  Even a 30-minute moderate jogging is not recommended?  In fact, I quite like cycling and will usually ride for 1 hour in the early morning before going to work.  Is this forbidden?

I know high blood pressure starts 140+ and I somehow approach this ceiling and don't know whether it is due to entecavir or other factors (I have a very bad mood after being diagnosed with bronchiectasis half years ago) since I have very normal blood pressure last September.  :(

Many thanks!

Regards,

Cyrus
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bronchiectasis

you can try liposomal vit c for that and see if it improves by 5-6 months of use
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Dear all,

I just got my week 12 result, Hbsag : 1.01 IU/ml. (before treatment was 456 IU/ml)

Please advise what I should do next to increase my chance of seroconversion .

Thanks a lot.

Regards,

Cyrus
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I'm so happy for you cyrus! You are on your way to clear the virus or probably cleared by now! God bless you..
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Congratulations Cyrus 131. So happy for you.
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Congrats Cyrus. Very good response. Just a quick question, the injection site, do you get bruising and how long does it go away?
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No or not much bruising observed.
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It is so great to see that your treatment is working for u. I'm currently in almost the same state as u were before u started IFN. But anyway, hope u get rid of hep b as soon as possible. Can't wait to hear good news from u!
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Keeping injecting PEG until get HBSAB.  
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Thanks for the response. Also, do you take any supplements/health food?

Just had my second injection. The first injection site still have some bruising.

My injection still need lots of practice. Not much fat to work around and the hand is too shaky and unsteady.

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Dear all,

This morning, my wife helped me to do the interferon injection.  When the needle was in my belly, she pull the syringe to see if there is blood coming out.  She did and saw no blood.  Then she performed the injection but when she pull out the needle, we found that trace of blood was inside the syringe.  Just want to know if the interferon was injected into a blood vessel, any adverse effect or will it render this injection useless?

Thanks a lot

Regards,

Cyrus
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Bleeding from small vessel. not significant.  You have to cannulate a vein properly like a medical train person to get any sizable volume into a blood vessel.  
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To Cyrus,

How is your other blood work like ALT and WBC/neutrophils level? Your treatment seems to be on the right, positive track and I wish you all the best.

Correct me if I am wrong but did you miss one dose because of flu?

Thanks.
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Dear Stefano and Studyforhope

I just got my latest qHbsAg result which indicates my level is <0.05 IU/ml as at 19 February 2014, meaning negative.  My last qualitative test on HBsAg and HBeAg was still positive as at 6 February 2014.

My questions are whether the threshold in determining positive / negative is different for the quantitative and qualitative tests?  

What should I do now?  e.g. check for whether I have Anti-HBs or to inject Hep B vaccine in order to achieve s-seroconversion?  If I do not develop Anti-Hbs, should I continue peg-interferon injections beyond 48 weeks?

Many thanks for your kind advice.

Regards,

Cyrus
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congratulations Cyrus .Thanks for posting the data .
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Hi Stef

The Hbsag levels of Cyrus and Otan were same . However Otan cleared it in 16 weeks . Whereas the Otan DNA levels were quite high at the start . Could it be the Simvastatin effect worked for Otan .

Thanks
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so happy that you cleared hbsag too, which week is 19 feb?

don t worry about difference in quant and qual, it doesn t matter and is not relevant here.now you need to monitor hbsab level and keep peg until a good level of hbsab is achieved

if you dont see an hbsab in 2-3months you can also try the following to stimulate immune system:
hbv vaccine
zadaxin
gcmaf
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also consider to keep entecavir for 6-12 months even when hbsab becomes detactable, there are no guidelines for this but researchers that cure patients this way keep antiviral for 6-12 months after peg is finished just to be sure no relapse
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there are 2 members here clearing hbsag in combos where simvastatin is present:
otan peg+sim
another member i dont remember now: tdf+sim+gcmaf

too little patients to say it helps but since we know it prevents hcc, fatty liver and has few sides if any, it can be tried by others to confirm

both otan and other member had low hbsag, i think this is the main factor for peg response but this said sim may have a role or not, we need to find out
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About 45 weeks.  Should I check the HbsAb level? I am afraid my doctor will not allow me to inject interferon beyond 48 weeks.
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you absolutely need to keep peg beyond 48weeks until we have good hbsab, check this in advance and look for another doctor if there is any trouble

i remember otan got n touch with a researcher/doctor in HK or singapore, check her posts, he was very expensive but studying and treating to make hbsab once hbsag is neg
he is using peg, zadaxin and hbv vaccine

or simply look for another doctor willing to go over 48weeks

the maximum peginterferon strength is after 48weeks, in the second year of use, and this is quite normal to use 96weeks on responders

you may also start the hbv vaccine or zadaxin before 48weeks if these are non prescription in your country
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Dear Stefano,

Thanks.  Since I have hep B since birth and I am now 40 years old, is my chance of getting liver caner and fibrosis the same as before?  Should I continue to have ultrasound screening of my liver every 6 months as before?

Best Regards,

Cyrus
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is my chance of getting liver caner and fibrosis the same as before?

no in any case, also data we have is too little to say hcc risk is increased, we may say this on cirrhotic patients.i suggest you have regular nagalase screening if nagalase is normal there is no way to develop cancer, it also takes very long time for cancer to develop after nagalase become abnormal

Should I continue to have ultrasound screening of my liver every 6 months as before?
yes and if you add nagalase monitoring too you can be sure to have no surprise
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Dear Stefano,

Just had a follow-up yesterday and got my latest blood test result

Dated : 11 March 2014
HBsAg : Negative, HBsAb : 22 mIU/mL

I will continue to take Entecavir 0.5mg for further 6 months.  Is this HBsAb level low and do I need to further boost the immune response by injecting vaccine like Otan did?

Also, I have injected interferon for 49 weeks and I still have 1 spare dose in my refrigerator.   Should I inject it in the coming week?

Your expert advice is highly appreciated.  Many thanks.

Regards,

Cyrus
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very good! Congradulations!!! By the way do you have data on you liver stiffness before you started treatment and now?
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Dear Andrey,

Before treatment is 4.2Kpa (Fibroscan) and this is my last test.  I have done Fibroscan recently.

Regards,

Cyrus
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this is fantastic!!! I wish my hbv could end up in this way!!!
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have last injection, of course

hbsab 22miu/ml is too low, it would be best to keep etv for 6-12 months and if hbsab will not rise to 200-250miu/ml it is best to have hbv vaccine

is your vit d level good?
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Congrates cyrus.
I am also chronoc hepb patient
my latest blood report are here
plzz give me advice how to cure hbv
Hbsag confirmation test positive.
Antihbc total Reactive (CMIA) 12.86
antihbc IgM non reactive.(CMIA) 0.5
Antihbs Non Reactive.(CMIA) 0.81miu/ml
Hbeag Non Reactive(CMIA) 0.36
Hbv Dna Undetechable(PCR) <3.6 iu/ml

ill wait for ur valuable comments
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Steff, what are your supporting points for keeping etv after testing hbsag neg on inf treatment?
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that s guidelines once hbsag neg and hbsab pos the antiviral must be kept to normalize and consolidate immune response (remember cccdna is still there)

i believe only italian guidelines took care of this, very few countries around the world are actually curing hbv patients and taking care of consolidation...maybe only few words about this by researchers/most expert liver specialists
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I think there is always chance for hbsag relapse even when you test neg after inf course and in order to decide weather you need to go for next peg shot or maybe even go prolonged course you need to monitor your hbsag kinetics while on treatment. Just imagine if you were still hbsag positive on week 44 and started bebing neg on week 48. Is it wise to stop inf right away? or maybe prolong inf for a couple of month or so?
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How exactly can one find a good, non biased,  knowledgeable doctor?? Thanks
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good to see you folks are getting good responses :)
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I HOPE THE DOCTOR CAN FIND CURE OF IT. I AM HOPEFUL TOO
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Dear Stefano and studyforhope,

Sad news indeed.  I rechecked my HBsAg on 10 September 2014 and got my result today that my HBsAg is 'POSITIVE' again i.e. my Hep B relapsed!

I have discontinued my interferon as scheduled (after 48 weeks) after I developed Anti-HBs in March 2014.  I have not ceased and still continued to take entecavir 0.5mg daily as a precaution advised by you.

I did not get the vaccines (which I am terribly regretted).  Kindly let me have your expert opinions.  Many thanks.

Regards,

Cyrus
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first of all check the level of hbsag and hbsab, after we have this result i would go for hbv vaccines, zadaxin or gcmaf if low.if high another round of pegintf

is your vitd25oh kept at optimum levels around 100ng/ml?of course this is mandatory for immune function and if low must be corrected as soon as possible

as to the use of entecavir or tenofovir i would wait for the expert opinion of studyforhope.i personally prefer tdf because more potent
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another thing i dont have time to read the full post now but if you had only 48weeks of pegintf i strongly suggest to restart it.the most potent effect of peg on immune system is between first and second year (not shorter or longer), so this might be the best choice togheter with vit d or simvastatin as some of us are trying
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did you check your hbsag in quantity again? By the way Paris2013 also relapsed after extremely low hbsag achieved by interferon and anti-hbsag development as well.
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Dear Andrey,

Thanks for drawing my attention to Paris2013 case.  The only difference between me and Paris2013 is that I achieved HBsAg undectable (I don't know whether it is equivalent to clearance) and then attained the Anti-HBs at 22mIU level (I know it is low but my doctor would not prescribe further interferon and I was too stupid to think I had already won the battle of HBV).  Now I was tested positive for both HBsAg and HBeAg.

I haven't checked the HBsAg quantity but will do so these few days.  What do you think about Paris2013's doctor about it is useless to repeat interferon as it appears that we (me and Paris2013) have no permanent control on the HBV.

Would studyforhope please kindly advise.  Many thanks.

This disease is indeed very frustrating!!!

Regards,

Cyrus
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My opinion is that your hbsag titer went below cut off level (<0.05) while paris2013 was 0.09 iu/ml almost below. Both yours and her immune system should establish permanent control of hbv but for some reasons that did not happen. Meanwhile you both continued taking entecavir after pegasys but it did not help to keep hbsag cleared.

See page 18 of below presentation: http://www.aphc.info/pdf/2014/Luncheons_13012014/S-251/Jorg_PETERSEN.pdf  

Some people clear hbsag with Baraclude mono without any relapse in the future, this is really possible while we have two members here that cleared hbs and relapsed. I already start thinking that hbsag relapse is irreversible.

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let us wait intil your quant hbsag comes back. if your dr does not want to give you more interferon then there is very little that you can do to change the course. taking antivirals will slow the regrowth of the infected cell number.

i think if you retreat later with ifn you will have a response again. It is the lack of the proper epitope tcell clone combination and an insufficient cytokine milieu to keep the tcell clone in an effective state that limits the permanent internal control.
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Dear studyforhope,

Thanks for your expert advice.  So you mean it is better to repeat another course of interferon?

Regards,

Cyrus
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ifn or likely better a course of zadaxin. if you are in hongkong, it is available there.
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Dear studyforhope,

Thanks a lot for your prompt advice.  While repeating IFN for another course is off the guideline in Hong Kong, I am not sure if there are doctors who will prescribe me a course of zadaxin.  Btw, how long is a course of zadaxin?

My doctor just commented the effect of repeating IFN is very limited in my case as "No one know if my immune response can be further enhanced by
repeated another course of interferon."

I think I will check my qHBsAg before considering my further treatment regime.  

Many thanks for all your support!

Regards,

Cyrus
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I know Cyrus that it is frustrating when you almost cleared but relapsed, however look at the positive side of it that you responded to treatment and you are more likely to clear than many of us who still have long journey
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you can try extended interferon course off lable or find doctor in Singapore for prescription (extended course is very normal there, I can recommend you a doctor).
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Hi there,

Sorry to hear that. I hope my next appointment in 4 weeks time is OK. My surface antibodies climbed from 55 to over 300 in 10 weeks (week 38 to week 48). Fingers crossed it remained so.

Just wondering that since Paris2013 did not experience any elevated ALT during IFN treatment. What about yourself? Did your ALT level goes up?

My ALT was still on 125 2 weeks after IFN.
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hei cyrus, sorry to hear that you relaplsed, but it is good you checked it and find out soon, i dont think it will be a problem for you to clear it, as you took so many years entecavir. i wanted to ask you if you remember, can you tell me your hbvdna or hbsag quant before you start taking entecavir ?
thanks .
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My ALT did go up to some 90+.

My pre-treatment hbvdna was undetectable and HbsAg was 456iu/ml.

My doctor is still skeptical about the effectiveness for another course of interferon in my case.  If I can't convince him, I will need to revert to more expensive private doctors.  Should I restart treatment and when?  I last finished 48-week interferon in mid March 2014.
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Yep, it's a tough break. IFN is no picnic really. Every week you have to man up and take the shot. You have experience in that now but are you willing to go through that again? I would imagine your HBsAg will be in the low level.

I would give it another shot. As it's been done by trials, IFN can be a 96 weeks treatment plan as well.

I also suggest many things to boost immune function such as Vit D3 daily (at least 3000iu daily), herbs like curcumin and garlic, regular green tea and lots of vege juice.
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once we know how much it relapsed we can say if re-treatment is urgent or not

for example if you relapsed to 10iu/ml it is very probable you will gain back immune control slowly

also try high dose vit d first making vitd25oh 100ng/ml and pth 10-20pg/ml (if target pth is not reached increase vit d to more than 150ng/ml, during this supplementation avoid milk and dairies and increase water to 2.5l per day, keep an eye on urine calcium too although 99% it won t rise

as to curcumin i dont know if that is ok, it has antinflamatory effect so according to the balance of immune system it can boost or suppress immune response.green tea, 4caps of cpffee per day and juices ok for sure
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Dear studyforhope and Stefano,

Just got my quantitative HBsAg result : 0.15IU/ml.  I haven't checked my Anti-HBs and so don't know whether I still retain the Anti-HBs at good level.

Grateful for your expert advice on what should I do next.  I am still on Entecavir 0.5mg daily.

Many thanks.

Regards,

C Y Or
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From my non expert advice, you are very lucky, definetly going to clear hbsag, but you need vaccine i guess and some treatment! That is a very very low quantity  Wait for the expert opinion  of our experienced friends here , stef and study
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continue peginterferon+etv plus vitamin d3 10.000iu daily

maybe try adding also simvastatin, hbv vaccine and zadaxin

i d say this is not a clear relapse, i guess immune system is still working on it but it is best to chose immediately what to do and pegintf is for sure the best choice to consolidate clearance
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It's unclear if this will stay low or slowly return to higher values even if Entecavir is continued. In my opinion,if you want to stabilize or seroconvert the hbsag zadaxin for about 6 month is the most promising option, better than peg ifn. You would see success also in clearly increasing anti hbs titers. It should be easy to find a doc in hong kong who will prescribe zadaxin to you.
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Dear studyforhope,

Do you need I still have detectable Anti-HBs?


Cyrus
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You might have a very low titre just above the threshold. It is not of major functional importance at this point. But the Tcell stimulation with Thymosin alpha/Zadaxin will likely get your Ab titre substantially up. Even then that is just mostly a good marker of improved Bcell function, but what matters will be the increased Tcell stimulation that will tend to attack and decrease remnant infected cells, a process that you cannot easily see or measure, but it will result in a neg surface antigen. there is also a factor of luck involved here, epitopes and matching Tcell clones  must be available for stimulation or might occur de novo.
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is zadaxin the best drug once we reach very low hbsag and some detectable hbsab?
or this combo might have more chances pegintf+ydf or etv+zadaxin+vit d3+hbv vaccine with aldara on skin where we inject vaccine?

thanks
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aldara on the skin where you inject the vaccine is a very promising approach, and very available. The injections should be done intradermally, maybe 6 to eight injections spaced about 1cm on skin that has been prepared with aldara 2 hours before and again immediately before the injection. the doses for intradermal vaccinations are less than for intramuscular. having zadaxin in the mix would enhance it further, a Canadian trial has proven that.

Strong data support the notion that at a very low hbsag Zadaxin can induce a more permanent seroconversion than peg ifn.
it is unclear if antivirals at this time are helpful or harmful for the final effect. I have seen a paper where the group with antivirals did much worse than the one without it at this stage. Maybe the slightly enhanced virion production at this low stage gives incentives to immune processes.
Vit D is beneficial at all these approaches. It is unclear if very high doses improve the situation further over just high doses.
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