Research supported antifibrotics - do they exist?

The problems of treatment failure for SOC/IFN nonresponders and the possibility of reducing future supercombo-SVRchances by introducing archived resistance mutations when using "Pseudomonotherapy" - (that is here defined as using  a single  antiviral agent that is not protected against resistance development by its combo with an IFN/riba component (IFN by definition in this scenario is not sufficiently effective in reducing viral replication so that all the burden to tame the adaptive quasispecies evolution falls on the antiviral)) together with the 61% and 65% SVR rates for the latest triple modality in Geno 1s, have raised concern and the awareness for the need for alternate/additional treatment modalities in many HCV patients and their health care providers. Waiting for future antiviral developments is one route frequently recommended, but for the patients  in current need, our repertoire of additional meaningful approaches needs to be carefully reevaluated. Using antifibrotics to halt fibrosis progression is one concept not proven in large trials but it might well be effective in many, because the mechanisms for fibrosis generation are not intrinsically linked to HCV persistence, but rather to secondary response mechanisms evoked in the chronically inflamed liver, with the stellate cell activation holding center stage in this scenario. The following is one of several possible add on modalities.

[Hepatitis Researcher]

In that context, here is another  “component” of a possible multiprong antifibrotic cocktail.

Polyenylphosphatidylcholine (PPC)is just one example of an excellent, well published, NIH grant supported, human study supported, renowned research institution conducted, well respected researcher directed, several time AASLD presented (including a presentation in the grand auditorium, not just posters!), totally nontoxic – generally health enhancing, in combination with IFN SVR enhancing – see below, very available in high quality antifibrotic.

What is the answer to the following questions:
Why are two leading hepatologist, that I questioned in this regard, not aware of it at all?
How many remember that I discussed and described this particular component of antifibrotic measures here at this board about 12 month ago?
How many use this particular item or are at least aware of it?
Who understands the critical difference between “lecithin” and this particular compound?

The following paper is not referring to PPCs antifibrotic capacities, but to its enhancing features to reach SVR on IFN therapy in HCV. This was not a small study – 176 patients participated, it was conducted under strict Germany guidelines. And remember, these were early days- no riba was included. But it is a small but important timeless piece of reality uncovered and now long covered by library dust.Combine it with the above and draw your own conclusions.


Hepatogastroenterology. 1998 May-Jun;45(21):797-804.

Polyunsaturated phosphatidyl-choline and interferon alpha for treatment of
chronic hepatitis B and C: a multi-center, randomized, double-blind,
placebo-controlled trial. Leich Study Group.

Niederau C, Strohmeyer G, Heintges T, Peter K, Göpfert E.

Department of Medicine, Heinrich-Heine-University of Düsseldorf, Germany.
[e-mail]

BACKGROUND/AIMS: Polyunsaturated phospatidyl-choline (PPC) has been shown to
reduce serum aminotransferases in experimental hepatitis. This multi-center,
randomized, double-blind, placebo-controlled trial evaluated the effects of PPC
in patients with chronic hepatitis B and C in combination with interferon alpha
2a or 2b. The diagnosis of chronic viral hepatitis was based on an abnormal serum
alanine aminotransferase (ALT) value (more than twice the upper value of normal),
viral replication and chronic hepatitis found on liver biopsy. METHODOLOGY:
Patients received 5 million I.U. (Hepatitis B) and 3 million I.U. (hepatitis C)
interferon s.c. thrice weekly for 24 weeks, respectively, and were randomly
assigned to additional oral medication with either 6 capsules of PPC (total daily
dose: 1.8 g) or 6 capsules of placebo per day for 24 weeks. Biochemical response
to therapy was defined as a reduction of ALT by more than 50% of pre-treatment
values. The responders were treated for further 24 weeks after cessation of
interferon therapy with either PPC or placebo. RESULTS: 176 patients completed
the study protocol (per-protocol population: 92 in the PPC and 84 in the placebo
group). A biochemical response (> 50% ALT reduction) was seen in 71% of patients
who were treated with PPC, but only in 56% of patients who received placebo (p <
0.05). PPC increased the response rate in particular in patients with hepatitis
C: 71% of those patients responded in the PPC group versus 51% in the placebo
group (p < 0.05). PROLONGED PPC THERAPY GIVEN TO RESPONDERS BEYOND THE CESSATION
OF INTERFERON THERAPY TENDED TO INCREASE THE RATE OF SUSTAINED RESPONDERS AT WEEK
48 IN PATIENTS WITH HEPATITIS C (41% VERSUS 15% IN THE CONTROL GROUP; p = 0.064).
In contrast, PPC did not alter the biochemical response to interferon in patients
with hepatitis B. PPC did not accelerate elimination of HBV-DNA, HBeAg and
HCV-RNA. CONCLUSIONS: In conclusion, PPC may be recommended in patients with
chronic hepatitis C in combination with interferon and after termination of
interferon in order to reduce the high relapse rate. PPC may not be recommended
for patients with chronic hepatitis B. In contrast to IFN and other antiviral
agents PPC does not carry major risks and is tolerated very well.

[Andiamo1]

Is there any way to get access to this through health food stores?  Does Lecithin  contain it?  

Thanks.

[Hepatitis Researcher]

Lecithin contains it in insignificant amounts, lecithin was a control substance in some of the trials, it was way inferior. You will find pure PPC from health food sources, if you look hard for it, I want to emphasize that this is just one example of a component, one leg of a possible multriprong cocktail that has realistic scientific support. Another leg is the reduction of metabolic stress as mentioned recently and previously and the reduction of proinflammatory LPS input to the liver from the intestines - the "eubiosis/probiotic/prebiotic" concept, also explained in detail previously and in much more detail about a year ago.  

[orleans]

Any one have links to the above mentioned? thanks, jerry

[Andiamo1]

In a practical sense, how does one reduce metabolic stress?  How does one reduce proinflammatory LPS?

Thanks for all this data.  You have certainly been a source of lots of great information.

[copyman]

i'm interested in what Andiamo asked you about reducing metabolic stress & LPS. also could someone with stage 1 on a bx benefit from taking Polyenylphosphatidylcholine WITHOUT interferon to keep damage to a minimum while waiting for the approval of the new drugs? thanks again for all the great info you provide here.

[mremeet]

I think the metabolic stress HR refers to is partially associated with obesity, overeating, smoking, drinking etc, lack of exercise and consumption of sugar or things that result in elevated blood sugar. The usual suspects. I seem to remember him discussing that, but obviously he should be the one to clarify.

The search function on this site leaves a lot to be desired. But I found a few links where HR discussed antifibrotics, although in my cloudy tx addled memory banks I think he posted a "seminal work" on the matter that I couldn't find. If anyone else has it please post it. This is fabulous info, we should be grateful to have access to it...I mean where else are we gonna get this stuff?? HR you rock man, HUGELY DUDE! Thanks again...

http://www.medhelp.org/forums/hepatitis/messages/44507.html

http://www.medhelp.org/forums/hepatitis/messages/44136.html

http://www.medhelp.org/forums/hepatitis/messages/44654.html

[scratchinghead]

So I google that long name:
"Polyunsaturated phosphatidylcholine" and got a ton of good links.
Only clicked on this one, and it is chock full of stuff. I guess that big word can be reduced to the word "choline":
http://www.woodmed.com/Phos%20Choline.htm

I remember years ago, when most of you were no taller than your mommie's knee :-() Dirk Pearson talked about the only way to take choline was in liquid form because it deteriorated in air when in powder form. He application was for brain fuel and weight reduction but here is the stuff on the Life Extension Foundation website. (it used to be only Twin Labs had it, now they don't). It's really cheap.
http://www.lef.org/newshop/items/item00541.html

Now, maybe I'm making big illogical jumps here, instead of big logical jumps. I could be way off and so tell me if I'm wrong:
PPC is choline is best taken as a liquid.

[scratchinghead]

and. . . for those whose computers are broken, here is a couple extracts from thiis link:
http://www.woodmed.com/Phos%20Choline.htm

Forms
• Choline is available as a soluble salt, most commonly as either choline bitartrate, citrate, or chloride, or as phosphatidylcholine in lecithin.

• Most commercial forms of lecithin contains only 10-20% phosphatidylcholine.

• Most supplements labeled as "phosphatidylcholine" contain only 35 percent.

• Some newer and more potent preparations contains up to 98 percent phosphatidylcholine. These more pure forms of phosphatidylcholine are preferred since they are associated with fewer gastrointestinal side effects. This is particularly true in the treatment of those conditions that require large doses of phosphatidylcholine (i.e., 15 to 30 grams) because low-concentration forms such as lecithin would be required in such large amounts that side effects would be nearly inevitable.

Intravenous form is also available. The liver is the largest organ of the body and receives the first flush of PC from an infusion. However an exchange of lipids is systemic with every organ, every neuron, every cell sharing the increased PC and the higher performing lipids (HUFAs). It should be expected that improved metabolic performance would also be systemic.

and last but not least:
Appendix: Food Sources of Choline

Choline and Choline Phospholipid Content of Selected Foods, in Milligrams per Serving Free



Food                            Serving                         Choline             Lecithin            Total Choline

Apple                           1 medium                     0.39                 29.87               4.62

Banana                         medium                        2.85                 3.26                 3.52

Beef liver                      3.5 oz                           60.64               3362.55           532.28

Beef steak                    3.5 oz.                          0.78                 466.12             68.75

Butter                          1 tsp.                            0.02                 6.80                 1.18

Cauliflower                   1/2 cup                         6.79                 107.06             22.15

Corn oil                        1 tbsp.                          0.004               0.13                 0.03

Coffee                          6 oz.                             18.59               2.05                 19.29

Cucumber                    1/2 cup                         1.18                 3.06                 1.74

Egg                              1 large                          0.22                 2009.80           282.32

Ginger ale                     12 oz.                           0.07                 1.11                 0.34

Grape juice                   6 oz.                             8.99                 2.11                 9.37

Human milk                  1 cup                            2.10                 27.08               10.29

Iceberg lettuce 1 oz.     8.53                             2.86                 9.06

Infant formula   1 oz.     0.818                           2.97                 1.38

Lecithin supplement      1 tbsp., 7.5 g.               NA                  1725                250

(commercial, powdered)

Milk whole                   1 cup                            3.81                 27.91               9.64

Orange                         1oz.                              13.24               107.35             27.91

Potato                          1                                  5.95                 25.97               9.75

Tomato                        1v                                5.50                 4.94                 6.58

Whole wheat bread      1 slice                           2.52                 6.57                 3.43

                        

(USDA: Composition of Foods. USDA handbook # 8. Washington DC, ARS, USDA, 1976-1986)

[Hepatitis Researcher]

No. its NOT just choline, very far from that. It is a polyunsaturated fatty acid attached to phosphatidyl-choline. I do not like to mention any brand names here, but this is too important to let it go into nowhere. Check the brand name hepatopro. This is exactly that PPC compound mentioned in the article above.

[scratchinghead]

whoa! I just looked at the food sources of choline and coffee (that's C-O-F-F-E-E) has more choline than anything but beef liver (bleah).

Starbucks, here I come!

[scratchinghead]

aha, thank you for setting me straight.
would it be safe to say that the choline in food would also have this fatty acid even though not an exact science?

Heading off to google "hepatopro"

thanks again

[Hepatitis Researcher]

No, lecithin ("choline in food?")was used as a control in the Charles Lieber trials and failed to give the same effect, not surprisingly, considering the importance of the fatty acid tail to be polyunsaturated for membane fluidity and functionality.

[GoofyDad]

I certainintly can't comment on the quality and purity - nor would I put HR on the spot by asking him to - but here's the brand I buy - which is a bit less spendy:  

http://www.vitacost.com/NSI-Phosphatidyl-Choline/cas-1


I also buy their resveratrol:
http://www.vitacost.com/NSI-Resveratrol

and a liver furmula:
http://www.vitacost.com/NSI-Healthy-Liver-Version-2

[drofi]

the study is from 1998 and unfortunately there is a bigger study, which was done in the meantime (2003):
PPC treatment for 2 years did not affect progression of liver fibrosis.
http://tinyurl.com/2ctmuq
http://tinyurl.com/ytct8a
A promissing substance might be mp-1021 from Metriopharm: http://tinyurl.com/274j8h

Regards, drofi

[scratchinghead]

Hey thanks! I love vitacost.

[scratchinghead]

Your Metriopharm link was in german. Act lieber!!

[jmjm530]

I noticed you've been loading up at the health food store since finishing treatment. Would you mind listing your current regimen (you can leave out all bowel movement -related products),  why you're taking, any clinical changes from the supplements, any sfx positive or negative.

Thanks

-- Jim

[gauf]

So the article from 2003 says it isn't helpful after all? No benefit in taking PPC? What's the scoop?

[Whrose]

the 2003 article on PPC was interesting but i am not sure if that particular study would accurately reflect the anti fibrotic potential of PPC because the population of the 789 patients in the study were alcoholics (hx of average 16 drinks/day) and when baseline liver biopsy taken the alcohol intake among paticipants were about 2.5 drinks/day including the hcv positive participants.
in conclusion this study may not reflect the potential anti-oxidant potential of PPC on a patient who has 0 intake of alcohol?

i also could not find literature on MP1021 and would love a english translation of this link if you are up to the task. also are you presently on this and have any personal biochemical or biopsy changes as evidence of its anti fibrotic claims?

thank you for your info.
Whrose

[Whrose]

thank you for the info on PPC.

i would think that anti fibrotic therapeutic regimes would be quite an important adjunct to liver disease in general and hcv in particular. sigh...i wish we had more evidenced based therapeutics in this area!
my question is this...how does one evaluate the true ingredients and bioavailabilty of PPC products? there are so many scams out there.

also if you have time (certainly our tx docs do not) could you give several clinically interesting anti fibrotic therapeutics that have some promise for many non responders in F3-4 class that are in limbo with failed treatments. we need more answers for these ones! for instance there was some excitement over sulfasalazine a while back. i feel a desperate need for some positive therapies to benefit this population of heppers.

best regards
Whrose

[Hepatitis Researcher]

It would be naive to assume that PPC by itself can halt the progression of fibrosis. But it certainly is one very useful component of a multiprong/complex approach in that direction.
To get a good feel for the overall effect of a substance, you need to study many publications in its regard and this substance has the power to contribute a certain degree of hepatocyte protection and reduction of stress signaling onto the stellate system by combining an effect on membrane fluidity and functionality with the local, membrane bound availibility of choline and methyl groups. You could consider it a membrane bound betaine or Trimethylglycine with improved lateral mobility due to its polyunsaturated membrane anchor.The alcoholics trial is dealing with a difficult patient population with doubtful compliance, particularly in a long term trial and more so when the simplest method to halt progresion vom alcoholic liver fibrosis is to stop drinking. So you have an ill defined behaviour in your trial groups, a secondary very strong result influencing variable ( voluntary drinking restriction) and - equally important - the limitations of the semiquantitative nature of determination of fibrosis degree ("measuring fibrosis") by the use of liver biopsy. In the end the picture is blurred to the extent, that you see "no statistical significant effect".
All in all there is too much evidence in favor of its possible contribution to antifibrosis, combined with its overall health beneficial effects and total nontoxicity as to not make it an oblkigatory component of an antifibrotic cocktail.

[GoofyDad]

Not much more to report - just the stuff above, plus cod liver oil, and a probiotic, oh and SAMe - but I haven't been taking that lately - just forgetting to. Sometimes I end up with a full spectrum multi-vitamin instead of the liver formula.

The why part is just trying to improve the old Stage 4 liver.  

[gauf]

per HR's last post. That is good enough for me, I'm getting PPC.

[Hepatitis Researcher]

whrose:
my question is this...how does one evaluate the true ingredients and bioavailabilty of PPC products? there are so many scams out there.

Yes and confusing the identity of one compound with the other by making it all "choline". Thaty why I indicated the one thats pure pharmaceutical quality PPC. There might be others offering the same, but I did not scan the vitamin market for that.

There is no FDA approved multicomponent antifibrotic therapy for advanced  fibrosis HCV patients with treatment failure in current or near future existence.Long term PegInterferon was just shown at the AASLD to be not effective.. So nothing can be recommended in a place like this. That does not mean that a combination of hepatocyte protective, inflammation protective measures/agents and ,very much in particular, stellate transdifferentiation signaling blocking +otherwise proven nontoxic agents are not likely to be effective in that regard. I spent 3 hours at the AASLD to explain those concepts and their practical applications to one individual in particular need. I can point to literature and specific concepts and some aspects of practical application here from time to time in a piecemeal fashion, which has been done and was mainly lost. I can say that the use of various internet liver protective websites is - with some proper information interspersed - mainly futile and totally confusing, possibly wiping out the few specifically effective components that a person was already using. Look at goofydad : He forgets his Same. But at least he takes his Resveratrol....

[Whrose]

dang...whats a compliant and serious consumer to do when evaluating a products claims.
when i visit a health food store i get overwelmed by the products let alone the web! the info given is usually by another ignorant expert. most sites have an expert doctor (usually a chiro into "natural" cures giving alot of unproven hype. often this has me saying good bye to the products.
i  need the biochemical evidence of a product as much as i need to know its purity and effectiveness.
i wish i were there in your 3 hour discussion at AASLD!

thanks  Whrose

[GoofyDad]

Duly reprimanded :)

And I forgot to mention the green tea extract too - which IIRC was presented in a study at last year's pilgrimage of the liverheads....

[Hepatitis Researcher]

Yes, well remembered from the last years liverheads pilgrimage- the green tea posters ( not the posters here, but the presentation at the AASLD 2006 in poster format) re its antifibrotic effects.

It is of course one of the legs/prongs/components I would like to be considered in the antifibrotic regimen that the various practitioners should recommend to their patients. We do not know what works best, I am eagerly looking for comparison of the various in vitro/animal model antifibrotic effects of the promising compounds - but that has not been done.

Note that the extrapolation towards an expected in vivo human effect from an in vitro study that examines eg Tumor growth factor beta one or Nuclear factor beta expression supressive effects in stellate cell cultures is difficult since the concentrations used in viitro and the actual concentratin that you can realistically achieve in the liver by x dosage can be very very different.

Also note that there are quite a few substances that are so nontoxic - like green tea - the FDA expression is GRAS (Generally Regarded As Safe) that taking fairly high amounts in order not to miss a possibly critical contribution to the overall antifibrotic effect is likely a sound and overall effective practice. Always assuming of course that your personal doctor knows about it and approves it. Not a bad idea, to ask him if he is aware of all the respective work regarding these substances, including toxicity studies, antifibrotic in vitro and in vivo trials and other important work that sheds light on the possible health or ill effects of a particular substance. To scan and digest the antifibrotic presentations at each years AASLD alone takes many, many hours and I would seriously suggest that much more time will be allotted for this poster viewing, to give at least a working chance to the conference attending practitionrs to get aquainted with this research and its potential practical consequences.

[Whrose]

i did a quick take on dosage for PPC. read therapeutic range of intake is 800-2400 mg daily, and 4-6 grams or higher for liver salvage. in your view what would be a therapeutic range for cirrhosis. note that hepatopro comes in 900 mg caps with instructions to take bid.

YES i wish that our treatment docs would spend more time scanning and digesting anti fibrotic regimes. most of the people i know are taking measures on their own in a hit and hope loop. i would like to see docs giving "prescription strength advice" to our hi fibrotic population. this is more important than ever as our greatest population of infection are with midlifers, with some having little time to wait for combos way down the road. i am heartened that you have interest in this arena and  privileged to have your wisdom.

[GoofyDad]

i did a quick take on dosage for PPC. read therapeutic range of intake is 800-2400 mg daily, and 4-6 grams or higher for liver salvage.

Have you got any links????

[Hepatitis Researcher]

If my child had cirrhosis I would advise him to take 4 of these capsules a day (as part of quite a few other things that I would advise to take/do ( better do/take!) my child in that setting). I would of course advise him to understand that this is just a nutritional supplement possibly beneficial to his general health and that no claim can or should be made that it has any capacity to cure or mitigate his cirrhotic liver disease at this point in time, until, by randomized, properly powered clinical trials whose results have been analyzed and scrutinized by an expert advisory panel a decision is made by the proper authority that such disease specific claims can be attached to such a substance.I would explain to him, that while he is in need of immediate treatment, the strict rules to attach such claims must be followed in  a world that is filled with quackery claims by people trying to financially profit from the need of the despaired.

[Whrose]

father knows best...LOL beware of the quacks and meatballs in life. and don't forget a penny saved is a penny earned. geesh i think i just saved alot on my car insurance!
hugs!

Goofy. request is http://www.woodmed.com/Phos%20Choline.htm

[Whrose]

BTW.....i am available for adoption  hahaha

[GoofyDad]

I'd need to like quadruple my intake to get into HR's family. Oh, well - I bet his double-wide ain't nohing like my Moma's. Once we get the roof fixed and the skunks outta the wall, it's gonna be sweeeeeeeet....

[viaduk]

Thanks for your helpful posts. I was wondering if you would be able to list what the other things that you would advise your child to do/take.  Again, thank you for the interesting information.  

[viaduk]

And all this time I thought it was "a penny saved is worth two in the bush."

[drofi]

Quote: "To get a good feel for the overall effect of a substance, you need to study many publications in its regard"

I would love to study many publications in its regard and would love to get links to better publications about human trials with PPC, tha the one I have posted. As you know the opinionleaders here in Germany want evidence based data. They will not accept as an argument, if I tell them that a very clever guy in a forum told has this opinion :-)
Any links to good human trials about PPC and fibrosis progression available?

Thank you in advance, drofi

[drofi]

"A promissing substance might be mp-1021 from Metriopharm: http://tinyurl.com/274j8h "

Sorry, the german link was for HR, he is able to read it. I do not have any english article at hand, but will try to get it. MP-1021 is an inhibitor of macrophages and their inflammatory effect. It already has a marketing authorisation from regulatory authorities in eastern europe.

[beamishboy]

may i suggest a bright blue tarp secured with fullsize truck tires...and them skunks are durn good eatin and mite just come in hand,esp if y'all selling the farm buying them there supplementations..        
that said i am following this train of thot w avidity and await translation into english and layman terms with eager anticipation...meanwhile i'm chowing down a porterhouse with dble espresso...

[Whrose]

AND.......it would be nice to know who is the manufacturer of the product one would be choosing.
i am a bit paranoid that somehow it would be from china and have strange chemicals within the preparation that may cause one to faint, seizure, or suddenly speak in tongues.
LOL, i am a cautious and discerning soul. sorry nutritional supplements cause me to question not only their value bio-chemically but the origin of manufacturing. after all this is big business and the dollar is worth alot of deceptions.

[scratchinghead]

yeah, I notice right next to LEF's scientific summaries of studies they put their links to "buy now!". The same with Vitacost.com. It seems like LEF and VitaCost never quote any studies about things that don't work. . . . ..

[gauf]

So, has anyone found the least expensive PPC that meets HRs' criteria?

[DoubleDose]

My question regarding PPC use for antifibrotic effect is this:  Would it make sense for someone who has been SVR for a few years, and who has stage two or three liver damage, to use PPC to help hasten regeneration or healing of the liver?   Would you expect the PPC to add any benefit to the ongoing liver repair that often takes place over time, after obtaining SVR status?

Also, would you recommend SAM-e to augment the PPC (is there any proven benefit to SAM-e?), or any other anti-fibrotic, or anti-oxidant be added to the mix, for the SVR.  I am specifically addressing the SVR who has stablized all typical blood test results, has persistently normal LFT's since ending tx.  I appreciate any insights or opinions you might provide.

DoubleDose

[Hepatitis Researcher]

Regarding “MP-1021” : A substance from Russia, with a codename by the company,  that could be good , nothing or bad. There is not a  single entry in the Pubmed library – probably because the substance, or substance class that underlies it, is simply not disclosed. All the Internet info is from financial new or company hype. Here is a good case that there is simply NO meaningful approach possible, with one exception; Go the German/European union data base and find the company as assignee and then scan the patents for this type of substance -the patent text will reveal what type of substance class is used here,  or what this substance is a derivative from.


A relevant portion of the German descriptive text on the website:

“In der jetzt ausgewerteten Studie wurde die Wirksamkeit einer 6-12
monatigen Standardtherapie bestehend aus Nukleosidanaloga und
symptomatischer Behandlung mit einer Kombination aus Standardtherapie
plus MP-1021 bei Patienten mit chronischer und klinisch manifester
Hepatitis-C der Genotypen 1a und/oder 3a verglichen.”

Translation :
“ In the study before us, in evaluating MP-102, a comparison was made between:

Effectiveness of a 6-12 month standard therapy (against  HCV) consisting of ( anti HCV?) nucleosideanalogs and symptomatic therapy
with
A combination of the above standardtherapy plus MP-1021

In patients with chronic  Hepatitis  C with clinically relevant manifestations of Genotype 1a and or 3a “

Thus according to this company, the HCV standardtherapy consists of nucleosidanalogs and symptomatic ( symptom mitigating) therapy.

To be sarcastic, in Germany the  HCV standard therapy apparently consists already of nucleosidanalogs – presumably advanced HCV Polymerase inhibitors ( obviously in combo, since they used the plural), no Interferon – they improve your clinical symptoms during therapy- with impressive results, the results can now, thanks to MP-1021, be further substantially improved.

All in all, as part of the evaluation process, the quality of the info presented in the context of a new therapeutic entity is an important component, particularly if there is nothing else to evaluate the substance.

Again, this might be an important, clinically useful inhibitor of macrophage/kupfer cell activation ( they used it in tuberculosis therapy in Russia, so probably it is an antiinflammatory agent.
Drofi,  If you could provide the above mentioned  patent analysis it seems to be the only available step to move forward in forming even a rudimentary opinion.

[Hepatitis Researcher]

Obviously it would make sense to first determine if your fibrosis has not regressed already, on its own , so to speak, before engaging in a costly more complex antifibrotic regimen. Something like this PPC/NAC/ALA/TMG/SAme/Silymarin/Catechin/Resvera/(Curcumin?) is probably a very good component of a minimum liver health regimen, always STRICTLY PROVIDED that the lifestyle and the metabolic and intestinal proinflammatory liver stress reducing measures are all in place . I have discussed both the metabolic and the intestinal stress to the liver - both extremely important, at previous times in the detail necessary to make sense of it.

If you want to know what actually and realistically- for you personally- inhibits the proinflammatory response of your Mono/lymphocytes considering your post tx autoimmune issues, there is an incredible lab in Munich , Germany, that will take your fresh blood/lymphocytes, stimulate them with state of the art immunology reagents and then run several independent rests of real time PCR quantitative gene expression ( measuring your respective messenger RNAs with RT PCR) of the main proinflammatory nuclear expression factors ( like NFkappaB) and Cytokines, like TNFalpha, plus Cox2, LOX,  under the influence of Resveratrol, SAMe, Curcumin, VitaminD3, Boswellia ( Loxin -Leukotriene producing enzyme supressing) and others to see if your very immune system will indeed respond to these antiinflammatory substances.  I flew to Europe to investigate this sytsem, needed to get hard data on the antiinflammatory effect of some of these praised inlammation quenching and often stellate cell transdifferentiation blocking  ( antifibrotic) substances.Quite an eye oppener.  But the blood has to be fresh, it is an ex vivo test. It certainly gives all these hyped rantings at the websites - look what goofydad has lifted recently from the bottom of the internet- an entirely new meaning if you have actual hard core high quality molelcular biology data that concern your personal proinflammatory nuclear expression factors and what GRAS substances can block them, in a %inhibition of  transcription fashion.

[merryBe]

I seem to recall in the lost regions of whats left of my brain that long before Durkson the dept. of health and agriculture both did extensive studies on choline. If I recall lecithin has 2 components, on choline, the other escapes me, which work and absorb best synergistically, like Vit. A&D do.

also while the need of these in the diet is entirely essential, the two concerns were concerning kidney function and gall bladder, as too much letchithin could lead to soft stones...

too little of course is deadly, and if memory serves me, the liver will make it's own lecithin out of other things if diet is low in it, it's that essential to life!.

But, the other alert would be that any fatty acid or fat based ingredient
has to be very fresh to not develop rancidity and do more harm than good.

I'm not sure about this and if it's an issue with the PPC. I'm assuming this has fatty acid?

if so:

So it might be advisable to anyone buying it to look for Fresh and Pure as opposed to Cheap.

could you elaborate on this aspect please HR??

[Hepatitis Researcher]

As mentioned before : PPC  its NOT just choline, very far from that. It is a polyunsaturated fatty acid attached to phosphatidyl-choline. "Lecithin" is sometimes used synonomous with phosphatidylcholine without the fatty acid, sometimes with it but it is a compound with A SATURATED fatty acid. And sometimes just with a lot of fat, without the phosphatidylcholine.

Correct,  it must not be allowed to be rancid (partially oxidized), because this will initiate a chain reactions of lipid peroxidations. This is real bad. Store it in the freezer until used. Take some in a smaller, airtight container and store that in the frig for daily use. Do not take the caps directly from the freezer, because a lot of water will condense inside.

Many of these questions have already been anwered ( not this particular one, but the comparison with "lecithin".)  It is important to read every line, which sometimes is hard with so much text.

[merryBe]

thanks for that clarification. I've been reading that during treatment fibrosis does not reverse much, so this may be a real helper.

also, if memory serves, the mucousa is largely made up of letithin components, and if my eyes, so dry they can no longer blink, (thanks to the Riba) are any indicator, I'd says the tx is using up large amounts of these compound as tx does use up seratonin at alarming rates.

perhaps this will solve my dry eye problem as well as help heal the liver.

other than rancidity are there any contraindictions you can think of.
For instance do these lipids aide somewhat in nodule formation? wouldn't want to help the fibroisis but increase the nodules.....

[Whrose]

i am curious and must ask. do you have a financial interest the mentioned compound?
thank you

[drofi]

Good morning,

I am far away to tell that mp-1021 has a proven effect.

But please don't mix it, you still did not tell any data for the more interesting question:

Quote: "To get a good feel for the overall effect, you need to study many publications in its regard"

I would love to study many publications in its regard and would love to get links to better publications about human trials with PPC, than the one I have posted.

As you know the opinionleaders here in Germany want evidence based data. They will not accept as an argument, if I tell them that a very clever guy in a forum told us that he has this opinion :-)

Here is the question again:
Any links to good human trials about PPC and fibrosis available? Any human efficacy trials for PPC available?

Thank you in advance, drofi

[CockSparrow]

Whrose - do you have a financial interest the mentioned compound
----------------------------------------------------------
I cant believe you asked that question.
CS

[drofi]

Quote: "To be sarcastic, in Germany the  HCV standard therapy apparently consists already of nucleosidanalogs"

Yes, it does. IFN and RIBAVIRIN.
Didn't you know that Ribavirin is a nucleosidanalog?
http://en.wikipedia.org/wiki/Ribavirin

[Whrose]

sorry. i believe it is a legitimate question. afterall docs have no problem in the medical forum with such disclosures, and should not here. it is an honest question. if the science supports this product i am very interested in it and so would many hepatologist! i respect HR and his kindness to come and talk with us and am grateful. i have learned from him and others in some cool discussions.

[evangelin]

I just can't thank you enough for taking your valuable time to help us with this information.  My husband is a twice non responder with cirrhosis. I know you aren't God and you can't know for sure it
will help, but your guesses are a whole lot better than mine.  I greatly appreciate your help.  
God bless you for this sacrificial use of your time.

[Tallahassee]

Whrose - do you have a financial interest the mentioned compound
----------------------------------------------------------

Like CS, I also can’t believe you asked that question!

Pick a Biochemistry book, or just Google and you will see the significance of these lipoproteins/ fatty acids/ etc. for healthy metabolism of every human being.  And of course, people with compromised liver function need more purified, easily absorbable form of all nutrients.

HR used his valuable time to help and educate us!  Oh, and you are -- oh -- I'm speechless.

HR, Thank you very - very much for all your help!!!

All the best, always!!

[scratchinghead]

What is PPC made from?

[Tallahassee]

HR,

Thank you very much for helping us!!!

I compared "Hepatopro" Supplemental content of 900 mg of PolyenylPhosphatidilCholine (or Polyunsuturated Phosphatidilcholine):

Total Fat  0.8 Gm
Saturated Fat  0.06 Gm
Polyunsaturated Fat  0.19 Gm  
Monounsaturated Fat  0.59 Gm
(for some reason the sum of unsaturated and saturated fats doesn't adds up, but this is not important).

The formulation above consists of 190 mg of Polyunsaturated fats or  approx. 21% of the total 900 mg softgel.

I found another product which claims that its 900mg of PPC consists of "up" to 70% of Polyunsaturated fats.  http://nutrasalpharmaceuticals.stores.yahoo.net/phoschol9001.html

I don't like the "up" word, but do you think this (2nd) product is more "polyunsaturated" so to say? :-)

As always, you are great!

Thanks a LOT!!

[GoofyDad]

HR - Thanks for your contributions - you are improving the lots of many people here.....


Talahassee - That formulation's on my radar screen too. I notice the investigatory trials they cite  don't mention the polyunsatoration ascect at all. I've email the merchant a question about that -  I'll post any response.

But here's a bonehead question: What's the significance of the polyunsaturated?

[Whrose]

spare me your lecture. i really am not interested.
my question was not defensive but honest.
your response was chastising and self reflective.

HR. to be clear. i join in the chorus with everone here and am grateful for your generous time and kindness. thank you and please i hope you are not offended by my questions.
if i could i would pay for conversations like you have presented.  thanks always.

[drofi]

Quote: "Pick a Biochemistry book, or just Google and you will see the significance of these lipoproteins/ fattyacids/ etc. for healthy metabolism of every human being."

Correct. Pick a Biochemistry book or just Google and you will see the significance of water for healthy metabolism of every human being. Does water help against fibrosis progression?
I get impressed from hard facts only and nothing else. Good clinical trials, no opinions.

[GoofyDad]

Your point is well taken, and your analogy good. The thing is - sometimes in the absence of hard facts, we need to apply conjecture and common sense. To extend the water analogy - imagine where we'd be if our ancestors awaited clinical trials before they'd drink water.

For me - I will look forward to reading any data that comes out re: PPC and cirrhosis - but since ppc is demonstrated harmless, with added health benefits, and stands an excellent chance of reversing fibrosis -- I think waiting for more data would be imprudent at this point. That's for me - everyone has their own approach.

Be well.  

[CockSparrow]

Tallahassee was spot on. HR was attempting to make us think outside the box so to speak and you questioned his motives.
CS

[Tallahassee]

A fatty acid molecule is monounsaturated if it contains one double bond, and polyunsaturated if it contains more than one double bond.

In simple terms: Imagine that you have four (4) arms (just like every carbon molecule, and carbon molecules are like a back bone for all organic matters).

Having 4 arms, you may hold 4 different people simultaneously with your hands -- this will be your "SATURATED" state, because you used up all your arms and can't possible to add any other person (or a chemical substance, for example, oxygen or hydrogen) to be held.

Now imagine that two persons left you and now you have two "free" hands.  Remember, you have a total of four arms (hands). So, instead of acquiring other new people (or chemical) for "holding time", you chose to use two hands simultaneously to hold two remaining people (who happened to be happy to be with you :-)

See, you are holding two people with TWO hands --- you entered UNSATURATED state  -- why? -- because at any given moment, if conditions are right, you may change your mind and grab "passing by" molecules of OXYGEN (for example) with your "double bonded" hands, without losing your original devoted two people (chemically speaking, without breaking your structure, or backbone).

Unsaturated fats have these "double" bonded connections - hands; thus making a molecule potentially chemically more active – at any given moment - let say olive oil exposed to heat -- and boom -- unsaturated fats became saturated with oxygen and looses its "healthfullness".

If fatty acid's molecule has one double bond -- it will be called monounsaturated fat.   If it has two or more double bonds - it will be called polyunsaturated fat.   As you can see, than more double bonds, than more likely a molecule will be more chemically active -- either it will be a protection from free radicals, or its ability to enter cell membrane to re-establish original cell structure,... or rebuild cells,... or just participate in the endless process of so needed bio-chemicals production (in this PPC's case --- for production of S-Adenosyl-Methionine, as one of the substances).

I hope this makes sense.  English is not my first language, I think I was lost in the midst of my "holding hands" metaphor.

If it is still does not make any sense, I will try later again :-)

But anyway, if one product has 21% of polyunsaturated fats and the other has "up" to 70%, I would like to know from what exactly "up" starts :-)

All the best!


Where double bonds are formed, hydrogen atoms are eliminated. Thus, a saturated fat is "saturated" with hydrogen atoms. In cellular metabolism hydrogen-carbon bonds are broken down - or oxidized - to produce energy, thus an unsaturated fat molecule contains somewhat less energy (i.e fewer calories) than a comparable sized saturated fat. The greater the degree of unsaturation in a fatty acid (ie, the more double bonds in the fatty acid), the more vulnerable it is to lipid peroxidation (rancidity). Antioxidants can protect unsaturated fat from lipid peroxidation. Unsaturated fats also have a more enlarged shape than saturated fats.

[Tallahassee]

"See, you are holding two people with TWO hands --- you entered UNSATURATED state"
________________________________________________________________________

Should read:   See, you are holding two people with TWO hands for each person (using all 4 of your hands for only two people) --- you entered UNSATURATED state .

[Tallahassee]

I guess, in life, if you hold somebody with two hands -- the union should be stronger :-)

But in organic chemistry -- the second double hand "just looking for a trouble" to get attached to something. :-)

[GoofyDad]

T'hassee: Unsaturated fats also have a more enlarged shape than saturated fats.

So that would explain what I was seeing at the beach all summer....

Thanks!!!!! That was a great chemistry lesson!

[Hepatitis Researcher]

I have absolutely none  financial interest in any of these compounds or any, even the slightest  connection with any of these companies that sell them. For some specific products i haven taken the time to investigate brand specifics with respect to purity, quality control and content, because there are big problems with many of these  If you carefully read this thread, you will see that I was hesitant to give out any brand names, but the confusion of this PPC with Cholin and lecithin made it necessary so that some who might want to try this, can actually proceed and will not waste their energy in the wrong direction.
BTW all the panelists/hepatologists  in the top level discussions in the satellite meetings and the presentations  have heavy financial interest/are beeing compensated by the pharmaceutical industry.

They have to disclose that now at the beginning of these discussions/presentations. Should they be excluded from presenting or medical community opinion forming?

How long would a meaningful discussion have to be to cover the deep problems, but also the importance of development of effective medicines powered by the drive of these investors/stockholders/executives? I cannot participate in these questions, since that takes real time and it takes real time to work on a knowledge base necessary to optimize the approach to these burning real life biology/medical questions that surround the treatment of Hepatis B and C and fibrosis progression..

[Whrose]

thank you for your response. yes i perceived you were hesitant and i really appreciate you giving the information. it will save alot of $ and frustration finding the best products.
to answer your question. no. they should not be excluded from presenting or medical opinion forming.
we pay our physcians well and i have high regard for their educated opinions, as i have for yours.
it is strange to me that others contribute motives to my question, as if i crossed over some invisible line when i feel comfortable with such questions and not out of the norm. i perceive also indignation at such a question. the response is always interesting and revealing.

best regards

[mremeet]

HR - PLEASE don't be offended, keep the good stuff coming. This has been a fascinating and perhaps even lifesaving discussion. Thank you for taking the time.

whrose - What you asked wasn't out of line, it was a reasonable question to politely pose. But HR has been visitng here on and off for about a year now, and he has been thoroughly vetted by many here who have either spoken to him on the phone and in some cases have met him in person for a consult/fibroscan. He's also been vetted by medhelp too. He's here to help us, and he has never, ever attempted to sell us anything, I can assure you. He has spent substantial amounts of his obviously valuable time really and truly helping desperately sick people by providing them with extremely valuable information that us mere mortals would otherwise never learn about. And he does it FREE OF CHARGE and always has since being here.

In short HR's a righteous dude, if you haven't been hanging out here that long you might not know that yet. But trust me he is, so lets avoid going down the road of even vaguely suggesting he's here to sell us something - believe me he's not. (and I'm damned wary of that kinda thing, trust me!)

[Hepatitis Researcher]

Re the polyunsatiurated side chain question - see above :  considering the importance of the fatty acid tail to be polyunsaturated for membane fluidity and functionality.

Now for the chemically oriented/interested : Why would unsaturated carbon chains make a membrane more fluid.? Why is oil oil ( a fluid as opposed to butter)   -because of the unsaturated state of many of its fatty acid esters.

The answer lies in the rigidity of such a carbon chain with double bonds between some of the adjacent C-atoms . It restricts the free rotational movement of the double bonded C atoms, making the whole molecule less flexible and adaptive. This in turn results in the fact that they are now less able able to cuddle up close to each other, wich increases their van der Waals Forces and energy gain. Thus they can move about easier and the cellular membranes are indeed to be considered as a two dimensional fluid, in which proteins, receptors and many molecules that need to interact with each other in chance  encounters have to be free to do so and with a low index of viscosity, because this will increase the speed, at which reactions of importance for the molecular physiology of membrane  bound can happen. That is one of the reasons why the omega-3 fatty acids have such fundamental health implications.

So we end up with the seemingly paradox that a more rigid molecule creates a more fluidy membrane!
And why do we get the omega fatty acids mostly from cold water fish? Because they feed on the cold water plankton, those unicellular organisms really need a lot of polyunsaturation in order not to have their membranes freeze up to a nonfluid nonfunctional state.

[scratchinghead]

Damn your good.

[Whrose]

thanks. i am a polite person and asked my question with due respect.
btw. i don't have a problem with financial compensation for brillance.
i am touched and amazed by HR's kindness and appreciate as much as any of you...truely! if i were in CA i would be knocking on his door with my check book open. i certainly recognize his excellent education.
again thanks for your very nice way to respond to me. you are a gentleman.

[merryBe]

thanks for the refrigeratant/rancidity tips.

you know now that I think about all this, I seem to recall lechithin being the primary ingredient in various mucousa...particularly the mucous that maintains the eyes.

which means, this suggestion may be more corrective of the Riba dry/itchy eye syndrome than any ointment. I mean it just makes sense if the liver is compromised it can't make enough of it's own compounds that the mucousal linings would all suffer....this could then explain people having the dry cough sides as well.
My eyes feel like someone poured wintergreen in them, or used a blow dryer....I think I'll be considering this PPC very seriously.

[merryBe]

since coffee remove far more minerals from your body than it adds since it is a stimulant/duiretic, and since with tx all stimulants are out, as you will find out when you start your Riba.....

then too, be it coffee, beefsteak of beef live, the key to obtaining this through food sources would be to keep all the other chemical considerations in mind.
like for instance, you do not want to increase your iron, as liver failure causes toxic levels, so eating the above mentions 3 item would add to this problem...

also the citrus increase can cause you to hold on to Iron.

I can see why HR recommended the pure PPC and not a food source, there's just way more than the one chemical you are getting otherwise, and the idea is to create the good, not do more harm.

[Hepatitis Researcher]

Thanks for the realistic and kind words. You are surely aware that "legitimate questions" sometimes, if the context has provided them already, are borderline unwise and inappropriate. Whrose, Would you ask your famous hepatologist if he gets paid by the pharmaceutical  companies? You could and you could also ask your severely overweight hepatologist why ihe is not taking care of himself, while recommending anti NAFLD lifestyles to his patients. It will make him more open to prescribe you off label NTZ/SOC on the basis of the conference presentations?No, of course, it will not influence him the slightest.

  The implication of financial interest is of course always that your opinion is shifted in favor of what you get paid for, and that is indeed - human nature, and an essential feature of evolution- often the case.The disclosure clause, now commonly used in presentations of medical material with financial implications, is supposed to help raise suspicion towards the opinions presented.


Mremeeet, Important contributions here, simply aimed at helping other people, like the taste of the Telaprevir pills that you once presented here to help some decide if they were in the placebo arm got knocked down with hostility by others who did not like the slightest air of criticism in that realm.I wonder if anyone else perceived that critical piece of info and  I personally like  the harsh , no nonsense approach to everything, including intolerance to smooth bull that you often displayed, properly, in my eyes, when it comes to treating a potentially deadly disease.

[Tallahassee]

HR,

Thank you very much for chemistry & medical lessons.

I'm still trying to figure out what questions to ask my GI tomorrow ... regarding my low IgM & IgG.  http://www.medhelp.org/posts/show/338367

If you recall, I'm about 6 months post tx (and Hep. C NEGATIVE!!!!) and developed IgM & IgG deficiency. You pretty much gave me peace of mind ... that eventually my bone marrow should recover.  You also said that I should me monitored by a Dr.

So, I'm trying to come up with tests to suggest to my Dr. for my follow up/ monitoring.  

You mentioned:
- Flow Cytometry for B-cells (+ surface IgM & IgG)?

- will I benefit at this time from "Quantative Measurement Immunoglobulins Isotypes" (in order to exclude other humoral Immunodeficiencies)?

- also "Immunoglobulin Electrophoresis"?
--- of course, it is all in addition to repeating CBCs test.

I recently read about IgM-IgG complexes and also B12-IgG-IgM complexes were measured in unique (?) cases with high B12 concentrations (and I have high B-12 levels – over 4000 in May of 2007).

If you recall, my latest RBCs became slightly more reduced ... and I went through mental “exersice” trying to eliminate other, more innocent, causes for my newly acquired anemia... I even took for a week Iron Gluconate, just to make sure that I don't have iron deficiency.

If you may think of any beneficial diet / supplements – please share it – I’ll be grateful forever

Since now, after the treatment, to ask Dr. for blood tests, it is like almost "pooling teeth", I must be very specific, precise, and present my case knowledgeably during my short appointment with the Dr.

Oh, how I wish now that after my biochemistry degree, instead of engineering, I went to medical school... Oh well...  But I decided (and told that to my husband!), if I'll recover and if we'll win lottery, I definitely will enroll to a Medical School, not for practicing medicine, just for more knowledge. :-)

All the best and THANK YOU!

[Whrose]

thanks again for viewpoint and your answer.
the disclosure cause the way i understand it is to expose bias. however when the bias is met with sound principles, does it matter?  we all benefit from the efforts that these conference presentations give to the medical community and ALL the dollars that support them. i don't care if the money came from the mafia!  we need dollars and we need answers.  if you had answered yes to my question how would that change the evidence and science behind all your words?
dear no i would not ask my overweight hepatologist why he is not taking care of himself. i am seeing him for his expertise and solutions to my problems, not as his judge to personal lifestyle habits. but i might make a comment to him in the context of concern if the right moment presented. as for my famous hepatologist and his financial backings to research. yes i would ask. i am curious about these things. it is always within ones right not to answer.  pharm companies that compensate these docs have picked the cream of the crop. it is to our benefit that their research is supported.
in fact i wish you had the $ backing your thoughts and research. prevention of fibrosis will be of such value to our community that it brings tears to my eyes to consider its potential! you are a very nice person and also a dedicated one with intelligence. i would leave my trust fund to dedicated ones like you.
thanks again for all you do.
warm regards

[scratchinghead]

Thanks! Make sense to me. Better start weaning myself off coffee.

[merryBe]

yes you are a huge help! It's not often anyone gets the benefit of a vast resouvoir of knowledge on their specific disease. I doubt any other forum in here is so blessed/

that said, got another huge question

I'm wondering HR could you comment on the cholesterol lower aspects of PPC.
Mine is123 total right now, and this, plus the supposed itchy skin reactions (with riba alreafy on board that's a yike) plus the PPC being a soy derivative (allergies for some) ( that's the only source?....well it becomes a little more of a puzzle....wouldn't lowering cholesterol be a possible containdication given the 123?

[Hepatitis Researcher]

Your cholesterol is low because your liver cells are hampered in their synthesizing activity.  It is not likely that PPC would further lower the total cholesterol in this setting. Plus this can easily be followed.
Yes, the PPC is made from Soy, and if somebody is allergic against soy, it is a no no to use it, like any other soy product.

[Hepatitis Researcher]

The knowledge regading PPC is mainly from Dr. Charles Liebers work, he has published several animal studies on the antifibrotic effect of this compound. It is also from abstracts at prior liver meetings, posters viewed there and a personal, over an hour discussion wit Dr. Lieber which allowed me to better judge his qualifications, trust his conclusions and get his ovrall " feel" for this compound. The rest is from what publications are available on Pubmed and the overall trend re lack of any toxicity, likelihood of contribution to liver health by concept and role in membrane biology. There are no further large human trials, since none will pay for those, since this is not an item where you can charge $20 per pill as with the antivirals and if you did, patients would obtain it from other sources once you would have spent the money to further prove its usefulness. I fully realize that this is not enough to convince any authorities in Germany or here ("evidence based medicine") to allow it to be officially labeled and indicated as antifibrotic , indeed, its contribution in this regard might be smaller that we think or even worst case, nonexistent. However, weighing all the available evidence, combined with the virtually nonexistent toxicity, the availability and its low cost it seems a valuable component to someone with inflammatory liver and/or  fibrosis. Please also note, that the above PPC trial tested its efficac y re SVR%  improvement, not antifibrosis, and it seemed well conducted to me. .

I did not comment prior to your request for further links, but first only to the other compound that you linked, since I can only do so much in my limited time.

The compound from the website, that you mentioned, might well work excellent against stellate activation vio reduction of macrophage /Kupfer cell activation pathways in the liver that play as you know a pivotal role in the profibrotic pathway. I am still interested in finding out -possibly from you with bettrer access to european patents-  if you have the time - what the chemical class and basis for this codenamed product is, to possibly get some first idea if it should be included in the antifibrotic compounds of interest list.. If you have access to the compound intself, you could send it to Antox Gmbh in Munich, which will determine its inflammation inhibitory potential for your very own or somebody elses lymphocytes/monocytes using state of the art assays for transcription intensity meaurements under the influence of this agent. If it would work well in that assay, one could next turn to the question of toxicity. The balance between effectiveness and toxicity is quite important in the pursuit and use of such antifibrotics. Totally harmless like PPC  - you can try it, not much lost. Totally effective and totally harmless:  buy stock before anybody elso knows about it. Very effective but very problematic as some  in pharmaceutical development pursued antifibrotics were and are : Weigh your risks, wait until  approval or halting of development.  

I have no personal bond or pride or any advantage from any of these antifibrotic "components".Nor can i precisely gauge the relative contributory power of any of these, I wish there were any side to side comparisons in the numerous animal trials done.  But I do know that the cocktail has worked very well, with dramatic reduction from cirrhosis to stage one fibrosis, confirmed by numerous fibroscans and a liver biopsy in at least two patient cases thus far.

[scratchinghead]

Any chance of getting a grant from somewhere to run a study of your own?

[Hepatitis Researcher]

Drofi:
Quote: "To be sarcastic, in Germany the  HCV standard therapy apparently consists already of nucleosidanalogs"

Yes, it does. IFN and RIBAVIRIN.
Didn't you know that Ribavirin is a nucleosidanalog?
http://en.wikipedia.org/wiki/Ribavirin

hr. Drofi. Sie wissen ,dass ich ribavirin kenne. Nichtsdestotrotz war die Ausdruckweise in der Deutschen Webseite unpassend und sachlich inkorrekt. Man haette sagen sollen Interferon und ja bitte, ein Nukleosidanalog ( das ja immerhin im Verhaeltnis zu Interferon wohl zweitrangig ist (mit einer direkten antiviralen Wirkung von 0.5 log im Schnitt). Diese unnoetigerweise mangelhafte Ausdruckweise in der kritischen Beschreibung der Vergleichsstudie spricht fuer unfachmaennische Bearbeitung dieses Textes, das werden Sie sicher auch so sehen. Gibt zu denken.
Nicht zuletzt stehen die kommenden Nukleosidanaloga als Polymerasehemmer nun auch  im Zentrum des Interesses und dann wird der Plural wohl eines Tages Berechtigung haben.

Alles in Allem sind viele Leute in diesem Forum ueberempfindich und ueberreaktiv.Wird wohl das Interferon und die fuer viele duestere Lage sein.

Viel Glueck und herzliche Gruesse. Wie ist die Lage jetzt bei Ihnen mit der VL Entwicklung?
.

[Hepatitis Researcher]

The key thing to watch is the appearance of any kind of neoplastic disorder - very unlikely. The exact reason why your Immunoglobulin subtypes  are somwhat out of line is very hard to find and I doubt that your doc will or can make many any specialized efforts in that regard. Even a flow cytometry test to see if - within your lymphocytes - the B cell population is on the low side is not a routine test.
The best available test for disturbances in your immune system/hematopoetic system is a bone marrow biopsy, but there is probably no indication for this at this point.Since clinically there seems to be no major rheumatologic disorder present, it will not be pursued by a rheumatologist.

The superhigh B12 level is strange, I assume you take no mega supplements of this, or you would have mentioned it.I am not familiar with any autoimmune disorder with immune complexes containing VitB12.

[GoofyDad]

Thanks for the lesson. I'm starting to get there.... but if you will indulge one more question, I'm still not clear on this: Is the advantage of the unsaturated PPC molecule vis-a-vis the saturated PC molecule that the PPC can slip into the membrane easier -- or is it that once PPC is integrated into a membrane the PPC enhanced membrane has more fluidity?

I wasn't much of a student - eight grade biology was the end of the line for me. That may help  explain my need for the applied sledgehammer learning technique......    

[drofi]

Lieber HR,
inzwischen bin ich in dem Umfeld hep sehr aktiv und bemuehe mich nur bestens nachpruefbare Informationen als Multiplikator weiterzugeben. Daher haette ich mich auch ueber gute Daten zu PPC gefreut. Natuerlich gibt es sehr viele Komponenten, die eventuell einen positiven Effekt auf die Fibroseprogression haben, und wahrscheinlich auch eine geringe Toxizitaet haben, aber das ist aus meiner Sicht keineswegs eine ausreichende Basis um verzweifelten kranken Menschen die Anwendung zu empfehlen. Beispiele sind Silymarin, antoxidative Vitamine, acetylcystein, ursodeoxycholsaure, colchicine, s-adenosysl-methionin und sogar carnitin. Im Grunde gibt es aber zu keiner der Substanzen wirklich überzeugende Daten. Ueber die Wirksamkeit einer Erhaltungstherapie habe ich mir noch keine abschliessende Meinung bilden koennen, die Ergebnisse der HALT-C etc sind enttauschend, aber es gibt ja etliche andere Studien, die dem entgegenstehen. Da bin ich noch abwartend. Hinweise auf moegliche Wirksamkeit von Substanzen reichen meiner Ansicht nach nicht aus für eine Empfehlung. Schon gar nicht in einem Laienforum, in dem so viele verzweifelte Menschen mitlesen, denen andere dann ohne Skrupel den letzten Cent aus der Tasche ziehen. Daher bin ich beim Thema Wirksamkeit und Unbedenklichkeit so kompromisslos. In Ihrem speziellen Fall trifft das aber sicher den falschen Ansprechpartner, denn Ihre Absichten sind ausschliesslich ehrenhaft, das ist mir ganz klar.
Mir persoenlich geht es gut, ich bin motiviert 72 Wochen mit  anschliessender Lowdose phase zu therapieren und bin zuversichtlich Erfolg zu haben.

Viele herzliche Gruesse, drofi

[mremeet]

I don't think HR is either subtly or overtly misleading us into believing that the substances he mentions are scientifically proven to provide benefit. He's only explaining (1) what some of the substances are, (2) the proposed theoretical mechanism of how it might work and (3) the low or essentially zero toxicity of the substances he mentions. He clearly states repeatedly that he does not have conclusive proof that these substances will positively slow, prevent or reverse fibrotic progression. He's simply making the best of what is now known and providing what could be lifesaving advice in the event the theory actually concurs with reality (there IS that possibility drofi!). In the meantime the substances are highly NON-toxic in the doses he recommends, and he also clearly stated to only take these substances under the supervision of a personal doctor (just to be on the safe side). He's been extremely responsible and we all admire and appreciate that he's willing to provide us with these thoughts. Everyone here knows there are no guarantees that what he's discussing will control or reverse their fibrosis or cirrhosis, mainly because he repeatedly says so, and says so clearly. As far as the $$ expense of these substances, I don't know much they cost but if I had cirrhosis and for whatever reason couldn't treat (or failed treatment), I'd spend a lot of money every year just for a reasonable and well thought out possibility that it might help to prevent my *death*, and to buy me more time until better treatment became available. If it turns out to be a waste of money, and all the theory turns out to have been for nought, in the truest sense of phrase - what difference would it make?

[mikesimon]

I think we are so very fortunate that HR takes the time to share his knowledge and insight with us. I fear we members may impose upon him to the extent that he decides to refrain from participation in our discussions and that would be a huge loss to this board. I think we should be careful that doesn't happen. Mike

[Forseegood]

here, here....

[frijole]

Mike, I agree with you.  It seems (not on this thread) that there is some groupie mentality here and that its excess could run off anyone.
frijole

[mikesimon]

When a post is in German and I translate it only to find there really wasn't very much to it I think things are maybe going just a bit too far.This is a public forum and don't we generally speak in English here so the vast majority will be able to understand? And I haven't anything against the poster or the German language. It is good for me to try to understand it but I will admit I needed to use a translation tool to really get it. I just thought someone should suggest that we lighten up a bit so I volunteered. Mike

[Forseegood]

guess I don't mind the occasional German...sorry...but I do think that Frijole's point about not wearing out Senor HR is a good one...not to be a hectoring Biaaach...but I think it's best to try and see if he's answered something first before asking (which I know is kind of tiresome considering the way this is laid out, but one should at least try - I think) so he doesn't end up answering the same questions over and over...I hope youre well Mike Simon...

[scratchinghead]

gazuntite! volkswagen! porsche!

[Hepatitis Researcher]

The polyunsaturated tail, not only improves membrane fluidity, but more importantly allows the PPC molecule itself, due to its stiffer , unsaturated backbone, to be less attached to its immediate membrane environment and move laterally and rotate much quicker around, serving its biochemical purposes in a more effective way. Please consider that the membranes in a cell are not just the surface membrane, but numerous inside membranes as well as in the double mitochondrial membrane.PPC will be in all of these.

[Hepatitis Researcher]

The main post to Drofi was in English, the extra one was in German, since it contained a response to a slightly emotional reaction on his part to my critical view of the German website that he posted with re to  the antinflammatory substance. The ultrafine nuances that i can use in the German language with him was intended to settle this very peacefully.

Thank you all for your good support and the friendly words.

[ruth709]

halo,guys....can anybody help me interpret the result of my med test a while ago...thnak you very much.

SGPT: 58.10   normal value should be 0-49 mg/dl
Hbs Ag Sreening Test: Reactive

Thanks again!

[GoofyDad]

HR - Thank you very much. Extremely enlightening.

Switching gears to the metabolic issues for a moment - what's your take on brown rice and whole grain pastas and the like - are they in the same verboten (see that!!) class as the rest of the starches?
----------------------------------------------
For all interested in PPC - here's how a vendor I contacted differentiates their PPC from PC...

Thank you for your recent inquiry and interest in PhosChol.  The prefix
"polyenyl" simply denotes that the phosphatidylcholine molecule is
polyunsaturated and is often abbreviated PPC.  PPC is used to describe
100%
purified phosphatidylcholine from Soy. There are no other competing
phospholipids in PPC.  When the term phosphatidylcholine is used in
studies
it generally refers to PPC, and therefore a purified
phosphatidylcholine.

Some studies will also refer to Lecithin being administered at 1.8 to
2.7
grams, and this is almost always referring to purified PC. Unless it
states
for example that a PC of 30% or an EPL (Essential Phospholipid) of 75%
purified PC is being used, it is almost always purified, pharmaceutical
grade PPC.
It is a huge nomenclature problem and very confusing.  

From a therapeutic perspective, PPC is vastly different than triple
lecithin, which is sold as Phosphatidylcholine.  Unless you are using
PPC
you are taking a phospholipid complex of some percentage of PC, usually
30%,
and a variety of other phospholipids.  This is important as only PPC
can
deliver a therapeutic dose of 1,2 Dilinoleoylphosphatidylcholine
(DLPC).

As for the taste of the liquid, it's certainly not sweet, but it's
definitely manageable to take and has a slightly medicinal and nutty
flavor.
It can always be mixed with something like applesauce, cottage cheese,
a
smoothie, juices, or oatmeal (once it has cooled) just to give you some
ideas.

[scratchinghead]

If you want to translate German to English go here.
It only does 500 characters at a time and isn't perfect. This was the first link I clicked on when I googled for "German translator":

http://translation2.paralink.com/


anywayGreysAnatomyisoverheadingtobedforevergratefultoallhepcresearchersthankyouverymuch

[mikesimon]

Thank you for your clarification. You bring us a wealth of information and you always conduct yourself as a gentleman. I feel I am in rarefied company when I read your posts.  Mike

[gauf]

Does this mean that PhosCol is the same as hepapro? Does it meet HRs' criteria? Thanks.

[TravelMom]

Hepatapro IS PPC.... This is a good product..

[gauf]

Yes, bur PhosCol is cheaper, so is it comparable?

[GoofyDad]

I really don't know. Just sharing some info I received on PC vs PPC. All things being equal - I'd say go with Hepatapro, as it's been vetted by our resident expert....

[Whrose]

quote: "PPC,NAC,ALA,TNG,SAme,silymarin,catecchin,resveratrol,curcumin, are probably a very good component of a minimum lover health regimen."

would you please elaborate on the recommended therapeutic doses of each of the above.

am starting to get it (although i wish i could pull up your discussions from a year ago regarding your lengthy explanation of the eubiosis/probiotic/prebiotic concept. the prevention of pro inflammatory LPS input to the liver from the intestines. will contiue to try

now i know i am the cow in the field for interupting this great discussion! all are welcomed to ring the bell on the cow. sigh

may i suggest......please consider writing a short reference book of nutrition and liver health and market it soon as possible! i would love to have it as a reference since you won't adopt me.

[Whrose]

ahhhh i meant liver.....not lover...LOL but then again i am a liver lover ;)

[Hepatitis Researcher]

Lost another lengthy post - landing in a spinal therapy center??
So briefly:
Your liver to lover slip of fingers was not so far off : These substances will definitely improve endothelial function - the production of NO............

[JRenquist]

Thanks so much for the info and for using your time to help us. I'm going to try the regimen you would use for your imaginary child, if I can find the 2 components I don't yet have. They have the hepatapro at iherb.com for 25% off retail. I usually find the best prices there.  S.

[JRenquist]

Never mind the last post.  They are out of it at iherb.com now (probably from everyone reading hepatitisresearcher's posts)  

[GoofyDad]

HR - You might consider copying long posts into notepad temprarily as a back-up - or start in notepad....


whrose: if you didn't see this...
http://www.medhelp.org/forums/hepatitis/messages/44479.html

[viaduk]

"But I do know that the cocktail has worked very well, with dramatic reduction from cirrhosis..."

Would you  be willing to elaborate on the therapeutic dosage for the various substances that you mentioned ealier in this thread?  I tried to find your previous posts regarding this approach, but the search function here is not very helpful.

Thank you.

[scratchinghead]

I googled the stuff and just picked one of the links and it has 2 sources for LEF PPC for $44 or so.
http://www.shopping.com/xCC-co900-price_range_30_90-softgels

[scratchinghead]

Thats the good stuff.

[GoofyDad]

It' also available at The Vitamin Shoppe bricks-and-mortar stores - about $38.50..

[scratchinghead]

The $44 prices include shipping and handling. So I bet we are about the same.
Heppy Thanksgiving!!!

[GoofyDad]

Somewhere in this long thread - or a spin-off thread - HR made mention of the relationship between liver and lover. As I understand the comments, some of the suggested supplements are known to boost Niric Oxide. Can we talk about the implications, if any, of this NO boost and an underlying portal hypertension condition?

Here's an interesting link that suggests boosting NO would be a good thing....http://www.utsouthwestern.edu/utsw/cda/dept37389/files/245390.html

And this one seems to contradict...http://cat.inist.fr/?aModele=afficheN&cpsidt=2138722

HR, can you share more of your enlightened analaysis?

[Hepatitis Researcher]

Here is your analysis:

The sum of improved metabolic lifestyle,

decreased intestinal toxicity/inflammation on liver and systemwide

and the combo of the various components of the liver protective antinflammatory and stellate system activation (TGFbeta and NFkappaB expression reducing) reducing supplements

will often lead to improved endothelial function as a welcome "side effect".

Endothelial function is a summary term for the various reactions of the endothelium to the stimuli that in normal physiology make it respond to demands in regional blood flow and other situations, like a damage to the vascular bed.

Of particular interest is the relaxation of arterial-vascular tone - by relaxing the smooth muscle ring inside the arterial wall-  in response to increased peripheral demand like in the coronary system, the leg muscles when you run up a flight of stairs and -of particular interest to men with diabetes and hypertension-  in response to sexual stimulation.

All these functions are achieved by the healthy, non dysfunctional endothelial cells releasing Nitrous oxide -NO- through activation of the endogenous nitrous oxide synthetase, provided all the pathways and molecular machinery is intact.

In endothelial dysfunctions many of the complex subsystems at play here work at suboptimal levels, leaving the patient with a nonrelaxing artery, so the heart and muscles etc. do not get enough blood flow increase, resulting among other problems,  in the now so famous ( By TV commercials) ED. Hence the liver/lover connection/slip that I referred to.



The "seeming contradiction" that  you are referring to , Goofydad is the fact that in advanced cirrhosis there exists a complex syndrome called  "hyperdynamic circulation", which contributes to the portal hypertension by increasing the blood flow into the splanchnic ( gastroenteric=guts) circulation, delivering more blood to the liver (with a decreased capacity/increased resistance) ,  that makes the portal pressure even  higher. In this situation there is
an increased overall production of NO,
not locally but systemically present,
by the inducible nitrous oxide synthethase, that reduces the bodywide vascular resistance
( but not in the liver!)
and leads to blood pressure reduction, cardiac minutevolume /output overload
and overall volume overload
and also sodium retention in response to that, so as to compensatory  increase blood pressure/volume, by the renin/angiotensin system, ( this can lead to ascites and spontaneous peritonitis, all complications of advanced cirrhosis)
and often to renal vasoconstriction in response to the accumulation of blood in the splanchnic ( gut) vascular bed
which can lead to the lifethreatening  "hepatorenal syndrome".

In this situation extra arginine means even more systemwide , nonphysiological NO production with aggravation of the syndrome as described.

This has little to do with the improvement in local endothelial function and local NO production, a vital part of normal human physiology often impaired in persons with obesity, diabetes, fatty liver, hypertension and chronic inflammation.

I think this is the dichotomy that you were hinting at. Not so easy to clarify that, but I did it as simple as possible.

[St. George]

I happened upon a substance about a year ago through my studies in chiropractic college when I was experiencing extreme liver inflamation (inflammation) from the disease.  It is a patented substance called Glisodin.  It is an enterically protected form of S.O.D (superoxide dismutase).  SOD is one of the   main antioxidants the body produces naturally along with glutathione.  SOD in the body displaces extra Nitric oxide and renders it harmless which in turn reduces inflamation (inflammation).  The problem with SOD is that when taken  orally stomach acids neutralize it and make it usesless but that is where Glisodin comes in.  It has a clinically tested delivery system that in studies raised Glisodin levels in older humans to levels seen in young adults.  Up until Glisodi SOD was only useful when delivered  by sub q injection because it bypassed the perils of the stomach.  I received so much releif from my symptoms whithin days of taking this substance.   I beleive that this product could be useful as an anti fibrotic agent.

[St. George]

oh ,and also a naturally occuring enzyme which may be purchased named nattokinase.  Read up on it.

[St. George]

Here is a link with info pertaining to nattokinase and its effect on fibrin.

http://www.raysahelian.com/nattokinase.html

[Hepatitis Researcher]

Glisodin is Superoxide Dismutase from Melons bound to a gliadin protein carrier. The Gliadin is a protein with multiple acidic Glutamic acid side chain molecules, that renders it undigestable in the stomach/upper intestines. This way the SOD is protected frorm digestion and a small amount of it is penetrating the intestinal wall possibly by some leaky gut phenomenon.

It is unfortunately burdened with the risk of developing a food allergy type of reaction to it.

[St. George]

here is a link explaining in depth the functions of glisodin Sod in the body and are backed by clinical studies.  Also, glisodin doesn't displace nitrous oxide as stated in my previous post, but rather modulates it.

http://www.glisodin.com/glisodin_monograph.php

[St. George]

Wouldn't you agree that the small percentage of people who may develop a food sensitivity to it would be offset by the releif of symptoms many would attain from it, not to mention the protection it would afford the liver.  Have  you heard of Glisodin in your research?

[St. George]

I didn't use Glisodin through my failed treatment but do you think it may have added some benefit to the battle?  Do you think SOD overall in any form(injectable) would have a certain synergy with interferon?

[GoofyDad]

Thanks for that. Like a good bowl of spinach - it will take a while to digest. At the risk of oversimplification - it sounds to me that the take away is: NO enhancement is generally a good thing - unless the liver is obviously past the 'tipping point'.....

[CockSparrow]

mikesimon-I feel I am in rarefied company when I read your posts
----------------------------------------------------------------------------
I feel like spending the next three days trying to figure out what was said.

Good way to learn though.
CS

[KettyJohnson]

Thanks for a healthy and helpful discussion, you may also check this link for more information

http://allnutri.com/nattokinase.aspx

[mhudnall]

Just giving a bump to a very good previous discussion thread on the subject of PPC by HR and others. I think many will be interested, if they haven't already seen this thread.

BTW, the recommended product line, Hepatopro contains 30% ethanol; a fact that is not hidden, but also not well disclosed. At the time of this thread it was probably the best product out there. However, there is a new product line available now that contains no ethanol and is high quality. If anyone is interested send me a private message and I will tell you the source.

[evangelin]

For those of you who weren't here to benefit from HR's posts, here is one of the many gems he left in the Medhelp archives.  It also shows you why it is difficult to give a cut and dried list of which supplements he said to take .  It came with very detailed and complex explanations in an attempt to help us navigate through that which had the potential of helping and that which did not.  PPC alone took a lot to explain . Anything with the name Polyenylphosphatidylcholine (PPC) was bound to be a little complex.  :>)  HR took a lot of painstaking time to explain why phosphatidylcholine nor choline were going to do the job of reversing fibrosis.  
This thread was really long and likely only the desperate will have the stamina to read all of it.  If you do, you will see that St. George posted quite a few times.  
I was in the desperate club when I spent days on end reading and studying to understand his posts.  
If you note my post above from 2007, it  shows me to be the same person as I am in 2011 except that Joe has one more TX failure under his belt.  Why would I not have great regard for him for the help he freely gave.  He was a "suit" and TX was first but he was a realist and understood the unmet need.

[JoieTan]

Back to the top post,

PPC may not be recommended
for patients with chronic hepatitis B.

So this one applicable to Hepatitis C only ?

[crossroadsec]

I was sold a bovine liver complex by an MD who practices natruopathy. I took 1/2 the bottle n then stopped when i began tx. My liver transplant Dr said as long as I was confident w the Dr n trusted his source, I could take it. It kind of scared me, but my cousin has known him for over 30 years and swore he used  high quality alternative meds. ESLD can make you leave no stone unturned
I LOVE this thread. I'm gonna shop....and get that coffee bean grinder out!  
Thanks for all this information!! Karen :)

[Mari5116]

I found this post very hepful awhile ago, now seeing again.
In 10/2010 I was F1-F2 stage fibrosis and in 5/11 had progressed to F2- bridging with few speta.  I'm waiting to treat in the fall VL 21 mill+.  I had read this post a while back while reseaching antifibrotics in hopes of finding something that could effect some change prior to tx.  I already take Life Extension products and the PCC for quite awhile, live a healthy lifestyle, workout, swim, bike, do yoga eat healthy fresh food and stilll progressed. I do like sweets but in serious moderation.
I came across a clinical trial using sho-sai-ko-to and then another article from Sloan-kettering regarding the same.  I asked the doc during the clinical trial interview if he'd ever heard of it and he said, yes, it works.  I saw a local acupunturist and discussed the ingredients with him.  there are seven igredeients. He sold me something that he says has most of them in it.  I'm so afraid that it may be getting too late and time may run out for my little liver.  All this obsessing and sometimes it just all feels like a crap shoot.  
Sorry just in a mood.

[thebadbambino]

You know what pisses me off. These doctors or acupuncturist seeing how deperperate you are and sell you crap that's not doing a damn thing. They all put the best ingrediants in there formuler but most of the time it's at such low dosages it will not help a newborn baby. Most of these substances doesn't even get absorbed by the body.  Just like milk thistle. Research how much gets absorbed.  Sho-sai-ko-to has some studies behind it and I'm sure they were poorly run but for a Doctor to say it works then never trust him. How the hell can he say that.