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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.
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Avatar universal
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
Avatar universal
MEDICAL PROFESSIONAL
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.


Avatar universal
MEDICAL PROFESSIONAL
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.
233616 tn?1312787196
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??



Avatar universal
MEDICAL PROFESSIONAL
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.
233616 tn?1312787196
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.....
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