Research supported antifibrotics - do they exist?

[Hepatitis Researcher]

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.
[email protected]

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.