Treatments, experiences, comments

[cajim]

Notes from "Chronic Hepatitis B: Preventing, Detecting, and Managing Viral Resistance" by Keeffe, Emmet B., Dieterich, Douglas T., Pawlotsky, Jean-Michael, and Benhamou, Yves in Clinical Gastroenterology and Hepatology 2008;6:268-274.

Full paper in http://www.sciencedirect.com/science/journal/15423565

1.  Monotherapy using lamivudine has the longest history of use and shows highest rate of resistance.  A 2003 study of 998 patients showed 65% lamivudine-resistance mutations in 5 years.  Lamivudine should no longer be used as monotherapy.

2.  Monotherapy using adefovir has 29% mutation probability in 240 weeks, according to a 2006 study of 125 patients.

3.  Entecavir is 100-fold more potent than lamivudine or adefovir.  In a 2006 study of 673 patients using monotherapy of entecavir 3% showed virologic rebound in 96 weeks of which 3 patients had lamivudine-resistant virus at start of treatment.  A 2007 study indicated that the cumulative probability of virologic breakthrough associated with entecavir resistance was  0.8% over 4 years.

4.  Combination therapy (CT) using telbivudine plus lamivudine and monotherapy (MT) using telbivudine alone in a 2005 comparison of 104 patients did not show a difference in effectiveness.

5.  Combination therapy (CT) using lamivudind plus adefovir and monotherapy (MT) using lamivudine alone in a 2003 comparison showed CT superiority: by week 52, CT group remained virally suppressed, HBV DNA levels increased in the MT group.

6.  Combination therapy (CT) using adefovir plus emtricitabine and monotherapy (MT) using adefovir in a 2004 comparison of 30 patients showed greater antiviral activity with CT.

7.  Combination therapy (CT) using lamivudine plus peginterferon alfa-2a, monotherapy (MT1) using lamivudine, and monotherapy (MT2) using peginterferon alfa-2a in a 2004 study of 537 patients showed 18% resistance with MT1 and 1% resistance with CT at week 48.

"A combination of 2 potent nucleosides/nucleotides with different resistance profiles may prove to be the optimal first-line treatment for chronic hepatitis B."

"Drugs such as entecavir and tenofovir have such low rates of resistance..."

"Current treatment of HIV infection is based on creating a high genetic barrier to resistance.  ...  Current guidelines for initial treatment of patients with HIV infection reflect that view by recommending a combination of 3 or more agents from different classes having different mechanisms of action.  ...  Although data are not available for all antiviral agents used to treat HBV infection, it is becoming clear that single-drug therapy may not provide a sufficiently high barrier to resistance."

[cajim]

I am waiting for reply from Beijing to see what they say about my after treatment lab results.

I am also seeing my US doctor on 07/21/08.

Will keep you posted.

Best.

[zellyf]

Well, cajim, I think it was a valiant effort and I appreciate your maverick approach. If everyone thought like me there wouldn't be cures for anything.   What's the next step for you?

[cajim]

My Experience with全息自灸疗法 (Whole Rest Self Curing Method)

Background:

1. My profile:  Asian, male, 49yo, with positive HbsAg, negative HBeAg, positive e-antibody, fluctuating HepB DNA PCR, highest being 487165 IU/ML, fluctuating ALT, highest being 123.
2. My lab tests:

12/21/06:  HEP B PCR QUANT = 107000 IU/ML
03/19/07:  HEP B DNA, ser/plas, PCR = 100316 IU/ML
02/29/08:  HEP B DNA, ser/plas, PCR = 487165 IU/ML

               ALT       AST ALT       AST
09/29/05:  40         28 11/30/07:  123       50
12/08/06:  31         25 12/31/07:  34         29
03/19/07:  31         27 02/29/08:  46         36
10/29/07:  87         49

Aim:  Find a treatment that can stabilize my liver condition without requiring me to be on medication for life and without having to deal with resistance.

Method:  Using全息自灸疗法 (Whole Rest Self Curing Method) and its accompanying oral drugs.

1. More about the method: http://www.medhelp.org/posts/show/473007?post_id=post_2700725
2. My doctor’s opinion: “I have no idea what it is and have no trust in it at all.”
3. My friend zellyf’s opinion: “I totally agree with your doc about the Chinese patch therapy.  China has an endemic HepB problem...if that patch worked it would be of great economic interest to China to make sure that therapy was available to everyone who might benefit.  There is no reason in the world why they would want to ignore a successful treatment.”
4. My friend stevenNYer’s opinion: “Sorry Jim but there is no cure.  Believe me, I've looked and those before me looked...no luck.  The are many formulas but unfortuately the only thing they really cure is a heavy wallet.  Elmer Fudd looked.  Bugs Bunny looked.  Porky Pig looked.  Daffy Duck looked.  All no luck.   Sorry....couldn't help myself....hahahaha.”
5. Pros and Cons for me:  a) I may not have to be hooked to antivirals like Baraclude for life and friends at this forum may benefit from my trial one way or the other:  if it works you could try too, if it doesn’t you know to avoid.  b) It cost me $2000, my insurance did not cover it and it cost me 3 months of not being able to use Baraclude and risk associated with the wait.

Administration:  Please refer to the picture under cajim profile.

1. The treatment consisted of the oral pills (B) and the patches (A); the former was 3 times daily after meal and the latter was 4 patches (C-E) every 5 days on both arms in turn.
2. Starting date 04/09/08; completion date 07/08/08; 4/17/08 felt a little heavy in liver area; 05/07/08 and for about two weeks felt general itching, had to scratch till a little bleeding in leg; 07/04/08 6:30am swelling sensation in liver area; 07/11/08 swelling/pain/sensation in liver area, not sure what it was.
3. Intake of pills and application of patches were generally timely with the exception that on 06/16/08 dinner pills were forgotten due to party at friend’s made up next night before bed and once or twice noted one of the bubbles on arm burst due to bumping against the door or a friendly pat on the arm.

Results:

My lab readings before treatment:  positive HbsAg, negative HBeAg, positive e-antibody, HepB DNA PCR 487165 IU/ML, ALT 46.

Chinese Patch Treatment from 04/09/08 to 07/08/08.

My lab readings on 07/07/08 after treatment: positive HbsAg, negative HBeAg, positive e-antibody, HepB DNA PCR 404736 IU/ML, ALT 57.

Discussion:  Sadly, there was no result that I hoped for, $2000 and 3 months down the drain.  At least, fellow patients can learn from my experience.

Conclusion:  StevenNYer is right, “The only thing they really cure is a heavy wallet.”

[cajim]

Referral 3.

As my three month trial of 全息自灸疗法 (Whole Rest Self Curing Method) is coming to a close, the Beijing hospital urged me to send them my after trial test results and gave me the contact information of patient 3, saying his treatment effect was not shown almost 1 year later.

Today I called referral 3 (Z), a 35 year-old Chinese man whose HBV status was diagnosed in 1998, after which he sought both western and Chinese herbal treatments with no cure.  In July 2007, a female relative of his who tried the patch and felt it worked recommended the patch to him.  Z tried it with modification: the hospital asked him to apply 3 or 4 patches every 5 days; he felt his body could not absorb so much at one time creating waste and changed to applying one patch a day; also the hospital asked him to simultaneously take some oral herbal medication; because he was in Guangdong where the oral medication was not found and because he did not want to buy it and have it shipped from Beijing, he eventually did not take the oral part of the treatment.  Two months later his lab results showed no change so he stopped.  In June/July of 2008, he took his company physical and found his HBsAg has become negative, the rest unchanged: HBeAb positive and HBcAb positive.

What do you guys think?

[stevenNYer]

Thought this may be a good idea:

http://www.medhelp.org/posts/show/492008

[cajim]

Strange!  How come I have C3 below under 6 and it does not show?

C3.  If inadequate response (HBV DNA >=2000IU/ml) then add a more potent drug and monitor every 3 months.

Could you add it at end of 6?  Thanks.

[cajim]

Notes on "On-Treatment Management Strategies for Chronic Hepatitis B" Clinical Care Options, by Ira Jacobson.

1.  "In hepatitis B, where treatment is usually long term and where viral resistance is a significant problem, the issue is not so much whether one can stop early because of either a high likelihood of success or the inevitability of ultimate failure, but optimization of treatment to ensure the greatest likelihood of long-term viral suppression with a minimal risk of resistance."

2.  "resistance is much more likely to occur when viral suppression is incomplete."

3.  "The clinical consequences of HBV resistance are extremely important. When resistance occurs, it puts the patient at short-term risk of a hepatitis flare, which is particularly of concern in patients with advanced liver disease, and at long-term risk, the progression to cirrhosis and hepatocellular carcinoma, even if the patient currently has mild liver disease. Resistance also complicates therapy because changes in the regimen are required and there is cross-resistance among the various HBV antiviral drugs."

4.  Early, Profound Suppression Leads to Greater Sustained Response:  The 2006 study of 1367 patients by Zeuzem S, Lai CL, Gane E, et al., "Optimal virologic and clinical efficacy at one year is associated with maximal early HBV suppression in nucleoside-treated hepatitis B patients." (Program and abstracts of the 41st Annual Meeting of the European Association for the Study of the Liver; April 26-30, 2006; Vienna, Austria.) showed that greater virologic suppression at Week 24 of telbivudine or lamivudine treatment was associated with superior clinical outcomes at Week 52.

5.  "To date, we have no data demonstrating additive viral suppression from combinations of HBV drugs,...so far, the viral suppression achieved with combinations represents the level of suppression attained with the more potent drug. The authors of this publication concluded that there is no basis for combination therapy at this time, except in established resistance, because of the data showing that adefovir plus lamivudine is better than lamivudine alone in lamivudine-resistant patients."  But, "even if combination therapy does not confer additive viral suppression, it may well prevent resistance from emerging in patients who are at risk of resistance because of incomplete viral suppression."

6.  Road Map for On-Treatment Management of Chronic Hepatitis B, Expert Viewpoint August 2007, by Keeffe, Emmet B.:

A. Assess for primary nonresponse at Week 12; go to B
B. Assess early predictors of efficacy at Week 24; go to 1 of C
C1.  If complete response (HBV DNA negative by PCR) then continue and monitor every 6 months.
C2.  If partial response (HBV DNA 60 to =2000IU/ml) then add a more potent drug and monitor every 3 months.

7.  Conclusion:

"In conclusion, we have seen a major shift from a reactive to a proactive approach in the prevention of resistance during hepatitis B therapy. We feel that we should not wait for virologic breakthrough, certainly should no longer wait for alanine aminotransferase breakthroughs to occur in patients taking long-term therapy and that we should not even wait for virologic breakthrough, but rather, in patients with residual viremia, at time points that might be associated with the emergence of genotypic resistance, we should check for that, we should become familiar, if we are not already, with the genomic sequencing assays that are available commercially and use them in this situation. Viral genomic sequencing should be done whenever viral resistance might be present, such as in patients with residual viremia at 1 year or beyond, and any time there is a virologic breakthrough.

The goal in all patients should now be HBV DNA undetectability. This is attainable in the great majority of our patients with currently available drugs. Residual viremia, and this represents the proactive approach to which I have referred repeatedly during this discussion, at pivotal time points should lead to a change in the regimen, such that one need not even wait to monitor for genotypic resistance, much less viral or alanine aminotransferase breakthrough. We have robust data now that give clear guidance in the case of several of our drugs as to what levels of viremia early in therapy, such as at 24 weeks, and I think we will see more data at even earlier time points, should make us think that down the line we are likely to sustain unacceptable risks of emergent resistance.

In patients who have residual viremia at pivotal time points, in whom we think the regimen should be changed, there is increasing emphasis among many experts about an add-on paradigm rather than switch, and increasingly the add-on paradigm applies to suboptimal response as well as to resistance, although I think there are more data bearing on this point in resistance, whereas the arguments in patients with suboptimal response are more theoretical, and we do need more data. I want emphasize that add-on therapy is always preferred in patients with established resistance rather than switching to another monotherapy."

[cajim]

Paid 13338 Chinese Yuan plus postage for the medication for a 3 month course of 全息自灸疗法 (Whole Rest Self Curing Method).  Will start tomorrow (04/08/08).

[stevenNYer]

Make no mistake about it...I would LOVE to be wrong on the no cure thing.

But you do have to keep in mind, that in place where there are hundred of million of people with HepB, there WILL be some who spontaneously clear (that 1 %) and 1% of hundreds of millions is still alot of people.  And they would all market their cure formula, which in the internet age, it's easy to do.  So I would say these testimonies are even perhaps REAL, but it doesn't change the facts.

[cajim]

Referral 2:  On 03/28/08, I talked to referral 2 (E), a 30 year-old gentleman  who was diagnosed with HepB  five years ago during a physical.   He tried different medications but the blood test results remained abnormal.  Two years ago, an acquaintance in the same town started on this treatment.  He visited the acquaintance and started this treatment that lasted 3 months at the end of which his blood test results became normal.  That was two years ago.  He had annual tests for the last two years and the results continued to be normal.  Even though his treatment stopped two years ago, he did take some Chinese liver protection meds per his doctor's advice until now.  As for his acquaintance who also received this treatment, the results were not as good as his.

[cajim]

I think you maybe 99% right, but I hope or wish you are wrong.

[stevenNYer]

Elmer Fudd looked.  Bugs Bunny looked.  Porky Pig looked.  Daffy Duck looked.  All no luck.


Sorry....couldn't help myself....hahahaha

[stevenNYer]

Sorry Jim but there is no cure.  Believe me, I've looked and those before me looked...no luck.

The are many formulas but unfortuately the only thing they really cure is a heavy wallet.

[cajim]

全息自灸疗法 (Whole Rest Self Curing Method)

Details in Chinese at:  http://www.yigan120.com/

Summery:  It is known that many treatments of HepB have the undesirable effect of developing resistance.  It is also known that all chemicals once in our bodies have to be detoxified by our livers which are already weak without this load.  Chemicals are not intelligent.  When they attack HepB viruses thay also attack liver cells.  Researchers have noticed that patients who got rid of the HepB viruses naturally after the acute period and subsequently became immune to HepB virus have roughly the same number of virus fighting cells (T-cells, B-cells, etc.) as patients who were unable to get rid of the HepB virus and subsequently became chronic HepB patients with the important difference that the virus-fighting cells in the former did their job and killed the viruses while the same number of virus-fighting cells in the latter learned to coexist with the viruses.  The Whole Rest Self Curing Method aimed at waking up virus-fighting cells in the latter to do their virus cleaning job.  By putting a pad on the arm for 8 to 12 hours, the Chinese herbal elements on the pad will wake up the virus-fighting cells.  The resulting varicella on the arm has many HepB virus fighting cells.  Take care not to break it for best results.  One treatment period is 3 months, cost between 528 and 792 Chinese Yuan (excluding postage)

Personal experience:  In an effort to understand this Chinese-Medicine based treatment, I contacted the hospital located in Beijing China (address and phone number at http://www.yigan120.com/) on 03/25/08.  According to their doctor, the treatment has no side effect.  I asked for the opportunity to talk to their former patients and was given a referral.  On 03/26/08, I talked to referral S, who was diagnosed with chronic Hep B 5 years ago after which he tried a number of treatments with unsatisfactory results.  Around October 2007 his cousin,  also a chronic Hep B patient, recommended this treatment to S.  Prior to starting the treatment, S's viral DNA count was a number x 10 to the 7th power.  The treatment lasted 3 months.  In February 2008, his blood test showed all negative results.  At present he is not taking any medication and his former swelling sensation in the abdomen is no longer present.  I asked if I could talk to his cousin.  After getting okay, he gave me his cousin L's number.  According to L, he had Hep B for a long time and had tried both Chinese herbal medicine and Western chemical medicine.  The frustration was that when he was on medication blood results would be good but when he stopped medication blood results would be abnormal again.  The Chinese herbal medicine had the additional frustration of being bitter and taking a long time to boil.  He almost gave up.  During a 6 month rest from work, he searched the internet and came across this treatment.  He went to the hospital and saw many patients like him being treated there.  He told the doctor his history and the doctor said he could try it for a treatment period (3 months) and see.  He went through the treatment and went for a trip.  While away, he did a blood test and was surprised to see the results to be normal.  After returning to Beijing he did another blood test and the results continued to be negative.  Then he recommended the treatment to his cousin S.

Comments sought:  Are you a patient from China who has undergone this treatment?  If you are, would you please share with this community your condition prior to treatment, your treatment, and your test results after the treatment?  Thank you.

[stevenNYer]

Indeed.  The goal is to learn and stay on top of the game.

[zellyf]

Good stuff, cajim!  Have you shown this to your doc yet?