Aa
the corrections
with apologies to J Franzen and in the interest of discouraging MH from nuking the original thread (which contains a lot of interesting data amidst the pointless bickering) ....
"Conclusion: Liver stiffness measurements with transient elastography suggest that 53% of patients with CHB and severe fibrosis or cirrhosis will experience regression of fibrosis after treatment with nucleoside analogs. "
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Lends some credence to the theory that SOC does 'give your liver a break.' Perhaps ribavirin potentiates more than just anti-viral benefits to the liver after all...
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Lends some credence to the theory that SOC does 'give your liver a break.' Perhaps ribavirin potentiates more than just anti-viral benefits to the liver after all...
stefano: I came across a couple of AASLD abstracts that correlate HBV antiviral therapy with dramatic reductions in FS score. Abstract 382 "Transient elastography for examination of cirrhosis regression among patients with chronic hepatitis B treated with nucleoside analogs "
with the full poster here:
http://trs.scivee.tv/node/1221
concludes:
"Conclusion: Liver stiffness measurements with transient elastography suggest that 53% of patients with CHB and severe fibrosis or cirrhosis will experience regression of fibrosis after treatment with nucleoside analogs. "
for 35% of cirrhotics the reduction was to F0-F1! This continues to amaze. Have you confirmed cirrhosis reversal with other indicators: platelet count, spleen diameter, APRI, INR etc?
Also abstract 367, "Reduction of liver stiffness of chronic hepatitis B patients by antiviral therapy" concludes:
"Conclusions: LS (liver stiffness) was significantly correlated with fibrosis stage in the patients with chronic hepatitis B, and was suggested to be useful to assess liver fibrosis stage noninvasively. Significant reduction of LS was observed in the patients treated with antiviral therapy and can be attributed to the regression of fibrosis. Increase of LS of the patients without antiviral therapy was observed and can indicate the progression of fibrosis."
and
"2-point or greater reduction of deduced stage by antiviral therapy was observed in 10 of 18 patients in whom LS at the 1st measurement was 10.7 kPa or higher and fibrosis stages were deduced as F3-4. "
For anyone wondering about HBV/HCV FS equivalence, see Abstract 1905
"In chronic hepatitis B, TE measurement reliably predicts the absence or the presence of significant and advanced liver fibrosis and exhibits similar diagnostic performance as compared to HCV patients. Our results validate the cutoff values previously proposed for HBV and HCV patients."
with the full poster here:
http://trs.scivee.tv/node/1221
concludes:
"Conclusion: Liver stiffness measurements with transient elastography suggest that 53% of patients with CHB and severe fibrosis or cirrhosis will experience regression of fibrosis after treatment with nucleoside analogs. "
for 35% of cirrhotics the reduction was to F0-F1! This continues to amaze. Have you confirmed cirrhosis reversal with other indicators: platelet count, spleen diameter, APRI, INR etc?
Also abstract 367, "Reduction of liver stiffness of chronic hepatitis B patients by antiviral therapy" concludes:
"Conclusions: LS (liver stiffness) was significantly correlated with fibrosis stage in the patients with chronic hepatitis B, and was suggested to be useful to assess liver fibrosis stage noninvasively. Significant reduction of LS was observed in the patients treated with antiviral therapy and can be attributed to the regression of fibrosis. Increase of LS of the patients without antiviral therapy was observed and can indicate the progression of fibrosis."
and
"2-point or greater reduction of deduced stage by antiviral therapy was observed in 10 of 18 patients in whom LS at the 1st measurement was 10.7 kPa or higher and fibrosis stages were deduced as F3-4. "
For anyone wondering about HBV/HCV FS equivalence, see Abstract 1905
"In chronic hepatitis B, TE measurement reliably predicts the absence or the presence of significant and advanced liver fibrosis and exhibits similar diagnostic performance as compared to HCV patients. Our results validate the cutoff values previously proposed for HBV and HCV patients."
"The trouble with discussing the efficacy of supplements is the same as for testing anti-fibrotic drugs. You can't really prove that your condition got better, or at least did not get worse, because of the supplements you used."
----------------
This made me think of the syndicated columnist ,Dr. Gott who has been around for a long time. He has from time to time reported on home remedies if they generally are considered harmless, and he has received and overwhelming amounts of mail reporting success. He had one he printed about using Vicks to cure toe nail fungus. The sad thing is, they sell a very expensive prescription drug to do this and it is even dangerous to the liver. The cheap little jar of Vicks actually works if you use it faithfully until the toenail totally grows out new from the bottom. I don't know how much the drug currently costs, but someone I was talking to yesterday said she considered it at one time but it would cost $500.00 and she decided to pass. Well, risking your liver is even worse than the money. Who would ever imagine a dumb little jar of Vicks would do the same job. Pretty funny really. :>)
----------------
This made me think of the syndicated columnist ,Dr. Gott who has been around for a long time. He has from time to time reported on home remedies if they generally are considered harmless, and he has received and overwhelming amounts of mail reporting success. He had one he printed about using Vicks to cure toe nail fungus. The sad thing is, they sell a very expensive prescription drug to do this and it is even dangerous to the liver. The cheap little jar of Vicks actually works if you use it faithfully until the toenail totally grows out new from the bottom. I don't know how much the drug currently costs, but someone I was talking to yesterday said she considered it at one time but it would cost $500.00 and she decided to pass. Well, risking your liver is even worse than the money. Who would ever imagine a dumb little jar of Vicks would do the same job. Pretty funny really. :>)
" our government passed a law recently that pharmacies are no longer allowed to carry supplements that make claims that are not proven. "
While on the face of it this sounds good, I wonder how it will work out in practice. One immediate result will be that some supplements will become unavailable, some forever and others until the requisite trials are completed. Others will simply change their marketing claims. When I look at my supplement bottles and bags, most of them do not claim to do anything and certainly not the thing I actually use them for.
Ofcourse, any clinical trial data would be very welcome
dointime
While on the face of it this sounds good, I wonder how it will work out in practice. One immediate result will be that some supplements will become unavailable, some forever and others until the requisite trials are completed. Others will simply change their marketing claims. When I look at my supplement bottles and bags, most of them do not claim to do anything and certainly not the thing I actually use them for.
Ofcourse, any clinical trial data would be very welcome
dointime
"The trouble with discussing the efficacy of supplements is the same as for testing anti-fibrotic drugs. You can't really prove that your condition got better, or at least did not get worse, because of the supplements you used."
----------------
Very true, it's the reality of Catch-22; if we choose one option, do we really know what would have happened if we had chosen another option? Here on the forum we have the luxury of conjecture in discussing personal experience and dissecting individual results that may or may not be supported by scientific evidence. As you pointed out, there's precious little data on supplements from a clinical standpoint. Hopefully we'll get to a juncture when enough collective information leads to scientific inquiry and data... it sounds hopeful that maybe Canada is taking the first step towards just such a process for testing supplements just as it does for medications (thanks for that info Trish). That's a process that we could well use here in the US to further utilize and understand all possible options in preventing and reducing fibrosis.
willing:
Thanks for extracting and exploring the relevant info -- you're on point as usual.
----------------
Very true, it's the reality of Catch-22; if we choose one option, do we really know what would have happened if we had chosen another option? Here on the forum we have the luxury of conjecture in discussing personal experience and dissecting individual results that may or may not be supported by scientific evidence. As you pointed out, there's precious little data on supplements from a clinical standpoint. Hopefully we'll get to a juncture when enough collective information leads to scientific inquiry and data... it sounds hopeful that maybe Canada is taking the first step towards just such a process for testing supplements just as it does for medications (thanks for that info Trish). That's a process that we could well use here in the US to further utilize and understand all possible options in preventing and reducing fibrosis.
willing:
Thanks for extracting and exploring the relevant info -- you're on point as usual.
Good to know because I always thought clinical trials are reserved for prescription drugs, at least here in the US. I'm glad to hear that we (the US) are looking into including clinical trials for other substances such as supplements since the market and science have grown so much in popularity in the last few years. It will truly be interesting to see how things work out. Currently supplements are considered food supplements only which means all you need to mfg in California is a PFR or a manufacturing license for processed foods. Of course I've always felt that supplements are out of their class being listed as foods especially when you read some of the claims made by some distributors and manufacturers.
"I don't think there is much of any evidence out there in the form of proper clinical trials because where would the funding come from? Who wants to prove that, for example, curcumin is anti-inflammatory when curcumin is commonly available and there's no big money to be made from it. So we are left with folk medicine and anecdotal evidence to act on or not, our individual choice. "
That's not quite true, at least not in Canada. I alluded to this in the other thread - our government passed a law recently that pharmacies are no longer allowed to carry supplements that make claims that are not proven. Therefore, there ARE actually clinical trials underway here by independent research firms hired by these companies to provide such proof so that their products won't be taken off the market. There are plenty of universities in my area and at least one of them is doing clinical trials on supplements. From what I understand, the U.S. is either thinking about, will pass or has already passed a very similar law?
That's a win-win for consumers and patients alike, as far as I'm concerned. Because of that law, there will actually be clinical data on these supplements.
That's not quite true, at least not in Canada. I alluded to this in the other thread - our government passed a law recently that pharmacies are no longer allowed to carry supplements that make claims that are not proven. Therefore, there ARE actually clinical trials underway here by independent research firms hired by these companies to provide such proof so that their products won't be taken off the market. There are plenty of universities in my area and at least one of them is doing clinical trials on supplements. From what I understand, the U.S. is either thinking about, will pass or has already passed a very similar law?
That's a win-win for consumers and patients alike, as far as I'm concerned. Because of that law, there will actually be clinical data on these supplements.
Well, in time I will know.
Variability results in random variable data points.
Lack of variability results in static data points.
Trends result in linear data points trending in an up or down direction.
The more scans I do, the more data points on my graph. In time it should be clear if there is variability in the method, no change in fibrosis, or a trend.
Variability results in random variable data points.
Lack of variability results in static data points.
Trends result in linear data points trending in an up or down direction.
The more scans I do, the more data points on my graph. In time it should be clear if there is variability in the method, no change in fibrosis, or a trend.
What I found striking about the claims in the original thread is the short time period involved. From a recent review (free access) on the challenges of measuring antifibrotic effects:
"The single greatest limitation in bringing new drugs for hepatic fibrosis to the clinical setting is a lack of sufficient methodology for measuring clinical trial end points, rather than a limited number of promising agents. "
and re bx:
"A real problem for liver biopsy (or any proposed technique to assess histology) is the ability to detect small changes in regression of fixed, fibrous lesions over the short time intervals associated with most controlled clinical trials."
http://www.nature.com/nrgastro/journal/v7/n1/full/nrgastro.2009.197.html
which points towards FS and serum-based tests.
For mudhall there was an 11.5 to 8.7 change over 6 months same operator/machine. For Bali very consistent readings of 5.9-5.6 over 5 months with different operators same machine and a previous contrasting 8.0 reading 8 months earlier (different op/machine), For Stefano the amazing 16.3 to 9 reduction over 7 months. All attribute the reduction to some combination of antioxidants. I saw a 12 to 10 (don't have exact scores at hand) reduction over two years and attribute it to random noise. Willb saw very good agreement in two FS 6.1 readings over 3 weeks, same machine different tech. It seems FS readings can be very repeatable over short time spans, less so over longer spans. Is there any real change in fibrosis level ?
Taking antioxidants to detour stellate cells away from scar-producing pathways and thus guard against fibrosis formation seems a sound strategy :
"Hepatic stellate cell activation is also promoted by other factors, including oxidative stress by-products (such as reactive oxygen intermediates), apoptotic bodies, lipopolysaccharide exposure, and paracrine stimuli from neighboring constituents, including Kupffer cells. Subsequent accumulation of extracellular matrix results in progressively thickened fibrous scar tissue, which leads to vascular dysregulation and regenerative nodule formation culminating in cirrhosis."
(same paper as above)
However fibrogenesis is known to be a very slow process. That the same process can be not only slowed down but very quickly reversed seems possible but hard to believe.
"The single greatest limitation in bringing new drugs for hepatic fibrosis to the clinical setting is a lack of sufficient methodology for measuring clinical trial end points, rather than a limited number of promising agents. "
and re bx:
"A real problem for liver biopsy (or any proposed technique to assess histology) is the ability to detect small changes in regression of fixed, fibrous lesions over the short time intervals associated with most controlled clinical trials."
http://www.nature.com/nrgastro/journal/v7/n1/full/nrgastro.2009.197.html
which points towards FS and serum-based tests.
For mudhall there was an 11.5 to 8.7 change over 6 months same operator/machine. For Bali very consistent readings of 5.9-5.6 over 5 months with different operators same machine and a previous contrasting 8.0 reading 8 months earlier (different op/machine), For Stefano the amazing 16.3 to 9 reduction over 7 months. All attribute the reduction to some combination of antioxidants. I saw a 12 to 10 (don't have exact scores at hand) reduction over two years and attribute it to random noise. Willb saw very good agreement in two FS 6.1 readings over 3 weeks, same machine different tech. It seems FS readings can be very repeatable over short time spans, less so over longer spans. Is there any real change in fibrosis level ?
Taking antioxidants to detour stellate cells away from scar-producing pathways and thus guard against fibrosis formation seems a sound strategy :
"Hepatic stellate cell activation is also promoted by other factors, including oxidative stress by-products (such as reactive oxygen intermediates), apoptotic bodies, lipopolysaccharide exposure, and paracrine stimuli from neighboring constituents, including Kupffer cells. Subsequent accumulation of extracellular matrix results in progressively thickened fibrous scar tissue, which leads to vascular dysregulation and regenerative nodule formation culminating in cirrhosis."
(same paper as above)
However fibrogenesis is known to be a very slow process. That the same process can be not only slowed down but very quickly reversed seems possible but hard to believe.
Just because I was wondering, I looked up HR's profile and found out he had 76 pages of posts from 2006-2010. That was a lot of help given! ..."riches beyond measure" -I like that.
Ev
Ev
I have found this site, Nutrition Data, very useful for research on foods. It gives an inflammation factor for each food and also a glycemic index.
http://nutritiondata.self.com/facts/nut-and-seed-products/3163/2
This example is the result for linseed which reads as strongly anti - inflammatory.
So there is helpful stuff out there, but not clinical trial quality. And as with everything else we have to use our discrimination as to how we can use it.
dointime
http://nutritiondata.self.com/facts/nut-and-seed-products/3163/2
This example is the result for linseed which reads as strongly anti - inflammatory.
So there is helpful stuff out there, but not clinical trial quality. And as with everything else we have to use our discrimination as to how we can use it.
dointime
The trouble with discussing the efficacy of supplements is the same as for testing anti-fibrotic drugs. You can't really prove that your condition got better, or at least did not get worse, because of the supplements you used. And you could disprove the efficacy of supplements by finding one person who deteriorated despite having taken the supplements.
I don't think there is much of any evidence out there in the form of proper clinical trials because where would the funding come from? Who wants to prove that, for example, curcumin is anti-inflammatory when curcumin is commonly available and there's no big money to be made from it. So we are left with folk medicine and anecdotal evidence to act on or not, our individual choice.
Stefano has me somewhat astonished too. Telaprevir does not have a European licence yet but he claims that people in Italy are getting it from research facilities. How is that? Out the back door?
dointime
I don't think there is much of any evidence out there in the form of proper clinical trials because where would the funding come from? Who wants to prove that, for example, curcumin is anti-inflammatory when curcumin is commonly available and there's no big money to be made from it. So we are left with folk medicine and anecdotal evidence to act on or not, our individual choice.
Stefano has me somewhat astonished too. Telaprevir does not have a European licence yet but he claims that people in Italy are getting it from research facilities. How is that? Out the back door?
dointime
Another thread just wonderful. MH did not nuke the first thread.
In fact it's very boring and tedious at this point but it's still there.
In fact it's very boring and tedious at this point but it's still there.
I was around when HR was posting and I never got the impression that he was promoting supplements in order to further his own interests. He made a big effort to answer our questions that were at the leading edge of the current research, and he contributed greatly to the collective knowledge of hepC on this forum.
So although I don't believe it was his aim, I hope he did get something out of all the work he did for us because the man has got it coming. Just my 2 cents worth.
dointime
So although I don't believe it was his aim, I hope he did get something out of all the work he did for us because the man has got it coming. Just my 2 cents worth.
dointime
Just a week ago I hear a great presentation in the hospital about the use of NAC in acetaminophen overdose. It is a part of the hospital protocol.
Good points and thank you for starting a new thread.
The evidence for NAC is the lives it's saved from acetaminophen overdose. That was good enough for me when HR suggested it as something to use to counteract my occupational exposure to solvents and then later explained the difference between r and l racemates. These two things are, to me, riches beyond measure. I have nothing but good to say about the guy and really couldn't contribute to the other thread coherently. (Lke that ever stops me, right?)
The evidence for NAC is the lives it's saved from acetaminophen overdose. That was good enough for me when HR suggested it as something to use to counteract my occupational exposure to solvents and then later explained the difference between r and l racemates. These two things are, to me, riches beyond measure. I have nothing but good to say about the guy and really couldn't contribute to the other thread coherently. (Lke that ever stops me, right?)
1) Re consulting : From the conflict of interest section of a recent paper
"Prof. Douglas Dieterich has served as a speaker, a consultant and is an advisory board member for F. Hoffmann-La Roche, Gilead, Bristol-Myers Squibb, Novartis and Boehringer Ingelhein."
http://www.ncbi.nlm.nih.gov/pubmed/19889142
Are Bali's Mt. Sinai FS scans less reliable because Dr. D is a consultant? Consulting is near universal among liver specialists
2) HR (and I am one of the many who have benefited from his posts, advice and FS) was ever so careful to not promote specific supplement manufacturers (with one exception in which he thought there was a particularly good PPC source as I recall). Why can't we follow this example? Instead of arguing about Zhang herbs, HepTech products or "HR's supplements" it would be far more helpful to discuss why specific agents are/are not helpful. What's the evidence for PPC/NAC/Resveratrol etc.
3) Why do we persist in regarding VL decline as significant when there is universal agreement among hepa's that this is meaningless other than as a tx-response indicator?
4) Similarly when correlating FS results with bx stage it would be helpful to know the source of the correlation (eg cirrhosis cutoffs range from 12 to over 14)
5) Stefano's results look near incredible. From documented compensated cirrhosis with FS 16 in March to a kPa of 9 in Oct, far below any cirrhosis cutoff. This is either error or amazing!
"Prof. Douglas Dieterich has served as a speaker, a consultant and is an advisory board member for F. Hoffmann-La Roche, Gilead, Bristol-Myers Squibb, Novartis and Boehringer Ingelhein."
http://www.ncbi.nlm.nih.gov/pubmed/19889142
Are Bali's Mt. Sinai FS scans less reliable because Dr. D is a consultant? Consulting is near universal among liver specialists
2) HR (and I am one of the many who have benefited from his posts, advice and FS) was ever so careful to not promote specific supplement manufacturers (with one exception in which he thought there was a particularly good PPC source as I recall). Why can't we follow this example? Instead of arguing about Zhang herbs, HepTech products or "HR's supplements" it would be far more helpful to discuss why specific agents are/are not helpful. What's the evidence for PPC/NAC/Resveratrol etc.
3) Why do we persist in regarding VL decline as significant when there is universal agreement among hepa's that this is meaningless other than as a tx-response indicator?
4) Similarly when correlating FS results with bx stage it would be helpful to know the source of the correlation (eg cirrhosis cutoffs range from 12 to over 14)
5) Stefano's results look near incredible. From documented compensated cirrhosis with FS 16 in March to a kPa of 9 in Oct, far below any cirrhosis cutoff. This is either error or amazing!
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