Aa
A friend sent this post-Reversing cirrhosis and fibrosis
http://news.bbc.co.uk/2/hi/health/5382172.stm
Drug 'may reverse liver disease'
A cheap and readily available drug could reverse severe liver disease, even in patients who find it impossible to give up booze, research suggests.
Sulfasalazine is currently used to treat arthritis and inflammatory bowel disease.
But a University of Newcastle team has found that it can also reverse the scarring associated with cirrhosis of the liver.
Liver disease is the fifth highest cause of death in the UK.
It would not be too optimistic to say this drug could halve that death rate
Professor Chris Day
It is estimated that up to 10% of the UK population have problems with their liver - and most are linked to lifestyle factors, such as heavy drinking and obesity.
Scientists had thought that the scarring associated with cirrhosis - known as fibrosis - was irreversible.
However, recent studies have shown that is not the case.
Now the Newcastle team, in tests on animals, have shown that sulfasalazine can aid the recovery process.
Regeneration
When the liver is injured specialised cells called hepatic myofibroblasts create scar tissue, and secrete proteins which prevent it being broken down.
In healthy liver tissue the scars eventually melt away and are replaced by new normal tissue.
However, in diseased tissue this process does not happen. Instead the scar tissue proliferates, and spreads throughout the whole organ.
The Newcastle team showed that sulfasalazine could aid recovery by blocking the production of proteins that keep the scar tissue cells alive.
They plan to carry out trials in humans, but already believe the drug has the potential to provide an alternative to a liver transplant.
The drug will initially be given to heavy drinkers who have given up alcohol, but too late for their liver to recover naturally.
If this proves successful, the medicine will also be prescribed to alcoholics who continue to drink but show a determination to fight their addiction by reducing their intake.
Professor Derek Mann, who led the research, said just a 5% to 10% recovery of the organ could have a huge impact on quality of life.
Efforts needed
Professor Chris Day, head of Newcastle University's School of Clinical Medical Sciences, said the drug was likely to work best on people who had made some effort to kick their boozing habit.
But he said it offered a potential solution to the tricky ethical problem of offering people who abused alcohol a liver transplant.
Some believe it is wrong to use organs that are in very short supply on people who have not demonstrated their ability to reform their drinking.
Professor Day said: "In that situation you may not give somebody a transplant, but you are not going to stop them getting a tablet, particularly if it only costs £10 a week.
"Cirrhosis is the fifth highest cause of death in the UK today, and it would not be too optimistic to say this drug could halve that death rate."
Professor David Jones, another member of the Newcastle liver team, said he and his colleagues regularly saw patients in their twenties with severe liver disease.
He said: "There is no point at which an alcoholic patient won't benefit from stopping drinking, but now we can actually help the healing process."
Anne Jenkins, of the charity Alcohol Concern, said: "The last 20 years have seen a significant increase in rates of liver cirrhosis, particularly among the 34-45 age group.
"Research that could help to reverse harm is obviously to be welcomed, but this work is at an early stage, and more needs to be done."
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/5382172.stm
my question is, why haven't we heard about this before
Drug 'may reverse liver disease'
A cheap and readily available drug could reverse severe liver disease, even in patients who find it impossible to give up booze, research suggests.
Sulfasalazine is currently used to treat arthritis and inflammatory bowel disease.
But a University of Newcastle team has found that it can also reverse the scarring associated with cirrhosis of the liver.
Liver disease is the fifth highest cause of death in the UK.
It would not be too optimistic to say this drug could halve that death rate
Professor Chris Day
It is estimated that up to 10% of the UK population have problems with their liver - and most are linked to lifestyle factors, such as heavy drinking and obesity.
Scientists had thought that the scarring associated with cirrhosis - known as fibrosis - was irreversible.
However, recent studies have shown that is not the case.
Now the Newcastle team, in tests on animals, have shown that sulfasalazine can aid the recovery process.
Regeneration
When the liver is injured specialised cells called hepatic myofibroblasts create scar tissue, and secrete proteins which prevent it being broken down.
In healthy liver tissue the scars eventually melt away and are replaced by new normal tissue.
However, in diseased tissue this process does not happen. Instead the scar tissue proliferates, and spreads throughout the whole organ.
The Newcastle team showed that sulfasalazine could aid recovery by blocking the production of proteins that keep the scar tissue cells alive.
They plan to carry out trials in humans, but already believe the drug has the potential to provide an alternative to a liver transplant.
The drug will initially be given to heavy drinkers who have given up alcohol, but too late for their liver to recover naturally.
If this proves successful, the medicine will also be prescribed to alcoholics who continue to drink but show a determination to fight their addiction by reducing their intake.
Professor Derek Mann, who led the research, said just a 5% to 10% recovery of the organ could have a huge impact on quality of life.
Efforts needed
Professor Chris Day, head of Newcastle University's School of Clinical Medical Sciences, said the drug was likely to work best on people who had made some effort to kick their boozing habit.
But he said it offered a potential solution to the tricky ethical problem of offering people who abused alcohol a liver transplant.
Some believe it is wrong to use organs that are in very short supply on people who have not demonstrated their ability to reform their drinking.
Professor Day said: "In that situation you may not give somebody a transplant, but you are not going to stop them getting a tablet, particularly if it only costs £10 a week.
"Cirrhosis is the fifth highest cause of death in the UK today, and it would not be too optimistic to say this drug could halve that death rate."
Professor David Jones, another member of the Newcastle liver team, said he and his colleagues regularly saw patients in their twenties with severe liver disease.
He said: "There is no point at which an alcoholic patient won't benefit from stopping drinking, but now we can actually help the healing process."
Anne Jenkins, of the charity Alcohol Concern, said: "The last 20 years have seen a significant increase in rates of liver cirrhosis, particularly among the 34-45 age group.
"Research that could help to reverse harm is obviously to be welcomed, but this work is at an early stage, and more needs to be done."
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/5382172.stm
my question is, why haven't we heard about this before
http://www.medhelp.org/forums/hepatitis/messages/43974.html
Yes I was referring to Mesalazine as the non toxic active moiety of sulfasalazine. Abstract #200 of the AASLD 2006 describes the specific inhibition of the nuclear factor kappa B by sulfasalazine by inhibiting the phosphorylation of serine 536, preventing the translocation of the factor to the nucleus. But additionally, it also acts like a pprgamma Agonist ( similar to rosiglitazone) , which, independently of the above mechanism inhibits stellate cell activation/transdifferentiation to the fiber producing myofibroblast status.
Thus, after using all the clearly harmless antifibrotic measures, it they would not be sufficient, as assessed by fibrosis quantitation, mesalazine would be an interesting candidate, fighting some of the autoimmune/overstimulation issues at the same time...
Yes I was referring to Mesalazine as the non toxic active moiety of sulfasalazine. Abstract #200 of the AASLD 2006 describes the specific inhibition of the nuclear factor kappa B by sulfasalazine by inhibiting the phosphorylation of serine 536, preventing the translocation of the factor to the nucleus. But additionally, it also acts like a pprgamma Agonist ( similar to rosiglitazone) , which, independently of the above mechanism inhibits stellate cell activation/transdifferentiation to the fiber producing myofibroblast status.
Thus, after using all the clearly harmless antifibrotic measures, it they would not be sufficient, as assessed by fibrosis quantitation, mesalazine would be an interesting candidate, fighting some of the autoimmune/overstimulation issues at the same time...
I just typed a long response to your question, accidentally hit the wrong button, and deleted the whole thing! So this time I'll keep it short.
I beleve HR was referring to Mesalazine as the "non toxic moiety of sulfasalazine". His response included a big technical explanation. This time I'll just quote his last sentence:
"Thus, after using all the clearly harmless antifibrotic measures, if they would not be sufficient, as asessed by fibrosis quantitation, mesalazine would be an interesting candidate, fighting some of the autoimmune/overstimulation issues at the same time..."
That's exciting news to me and that's why I printed it out, thinking I might show it to the doctor at some point.
I beleve HR was referring to Mesalazine as the "non toxic moiety of sulfasalazine". His response included a big technical explanation. This time I'll just quote his last sentence:
"Thus, after using all the clearly harmless antifibrotic measures, if they would not be sufficient, as asessed by fibrosis quantitation, mesalazine would be an interesting candidate, fighting some of the autoimmune/overstimulation issues at the same time..."
That's exciting news to me and that's why I printed it out, thinking I might show it to the doctor at some point.
"There is a less toxic deriative of it now" Wonder how we could find out what that is?
http://grants.nih.gov/grants/guide/pa-files/PA-07-361.html
Also, Dr Day from the article is conducting research under an NIH grant in Los Angeles - maybe we could send off the intrepid Forseesnoop to investigate.....
Also, Dr Day from the article is conducting research under an NIH grant in Los Angeles - maybe we could send off the intrepid Forseesnoop to investigate.....
I remember the discussion about sulphasalazine. I was really interested in it because my husband has cirrhosis. I was so interested that I printed out some of HR's comments, so I'll try to type out some of his comments:
"I have my eyes on sulphasalazizne since quite a while, it is an old drug against rheumatoid syndromes, Crohns etc and works quite well with very low side effects. Interestingly, there was an abstract now in Boston about a very particular specific and unusual molecular mechanism of sulphasalazine that blocked the activation of stellate cell transdifferentiation - that is fibrosis activation. Thus all you said about it is quite appropriate. There is a less toxic derivative of it now available. The potential importance of these antifibrotic measures in svrs or non SVRs can hardly be overstated. the problem is that large trials are needed to bring this beyond an experimental "off label" use."
The date of this post was 12/01/2006 so maybe somebody would know how to find the entire thread and post a link.
"I have my eyes on sulphasalazizne since quite a while, it is an old drug against rheumatoid syndromes, Crohns etc and works quite well with very low side effects. Interestingly, there was an abstract now in Boston about a very particular specific and unusual molecular mechanism of sulphasalazine that blocked the activation of stellate cell transdifferentiation - that is fibrosis activation. Thus all you said about it is quite appropriate. There is a less toxic derivative of it now available. The potential importance of these antifibrotic measures in svrs or non SVRs can hardly be overstated. the problem is that large trials are needed to bring this beyond an experimental "off label" use."
The date of this post was 12/01/2006 so maybe somebody would know how to find the entire thread and post a link.
here is some older news (from 2002)
"Reversibility of cirrhosis in patients cured of thalassemia by bone marrow transplantation."
of course, this particular disease is different from HCV. Nevertheless, interesting study.
http://www.medscape.com/viewarticle/433615
http://forum.lowcarber.org/showthread.php?t=73084
"Reversibility of cirrhosis in patients cured of thalassemia by bone marrow transplantation."
of course, this particular disease is different from HCV. Nevertheless, interesting study.
http://www.medscape.com/viewarticle/433615
http://forum.lowcarber.org/showthread.php?t=73084
I nearly always get responses - I guess in the end it's the fart jokes that win 'em over.
You know - since the stuff definitely seems to affect a core aspect of the liver's ability to repair itself (a very integral piece of it's existence), I cn see how it's possibl trials could expose more harmm that good to those with significant damage... who's to say. Yes it seems safe for most folks, but with identified activity within the liver - I'd be inclined to take the conservative approach on that.
HR suggested I loose weight, eat like a liver evangelistt, excersise for an hour+ a day, and give that approach some time before even considering more agressive measures. He correctly points out that there's no risk, and these activities would also benefit all other aspects of my health.
Popping pills sure is easier though.
You know - since the stuff definitely seems to affect a core aspect of the liver's ability to repair itself (a very integral piece of it's existence), I cn see how it's possibl trials could expose more harmm that good to those with significant damage... who's to say. Yes it seems safe for most folks, but with identified activity within the liver - I'd be inclined to take the conservative approach on that.
HR suggested I loose weight, eat like a liver evangelistt, excersise for an hour+ a day, and give that approach some time before even considering more agressive measures. He correctly points out that there's no risk, and these activities would also benefit all other aspects of my health.
Popping pills sure is easier though.
Hey, Great move e-mailing that guy! I am a little surprised he returned it. Trials in a year huh? This is something worth keeping up with. Being able to reverse damage would be HUGE!! Wish we could poll a lot of heppers that also had arthritis and take sulfasalazine to see how thier livers were responding. w.s. Have you had a bx lately? How long ago? I am sure all would be interested. jerry ps It might not be " appropriate" to take this stuff at this time but heck it also is not "appropriate" to let ones liver to go to hades in a hand basket either!
Lactulose has no impact on fibrosis or cirrhosis
Supposing there was evidence that NH4 (ammonia) causes cellular swelling and oxidative damage in the liver. Would you then agree that using lactulose to bind and excrete the NH4 might lessen liver stress and aid the damaged liver in healing?
Supposing there was evidence that NH4 (ammonia) causes cellular swelling and oxidative damage in the liver. Would you then agree that using lactulose to bind and excrete the NH4 might lessen liver stress and aid the damaged liver in healing?
the small organnic acids from lactulose bind water and this is the reason to use it as a stool softener. It is a very good factor to improve the quality of the intestinal flora, because Bifidobacteria and Lactobacteria are better L.-metabolizers than Gram-negative (eg. Salomonella).
IT is a great stuff, the most important sides result from the fact, that it is metabolized to gas to :-) especially during the first weeks of treatment, before the flora adapted.
IT is a great stuff, the most important sides result from the fact, that it is metabolized to gas to :-) especially during the first weeks of treatment, before the flora adapted.
Lactulose is a dissacharid (similar to lactose, the sugar from milk), which is not digestable by human enzymes. In the Large Intestine it is metabolized by the symbiotic bacteria to small acids, which react with NH4 (from proteins) to give a salt, which is excreted. Less NH4 enters the blood system and brain. NH4 is one of the important reasons for brain fog, especially in late stages.
Lactulose has no impact on fibrosis or cirrhosis.
Hmm, difficult to explain complicated facts in a foreign language.
Lactulose has no impact on fibrosis or cirrhosis.
Hmm, difficult to explain complicated facts in a foreign language.
I emailed a researcher quoted in the article and received this response.....
The work described in the article is entirely at the experimental stage at present, no clinical trials have been done on this drug and therefore it would be entirely inappropriate for anyone to take the drug for liver disease at present. We are hoping to start trials in the next year or so with the prospect of treatment perhaps five or six years off.
The work described in the article is entirely at the experimental stage at present, no clinical trials have been done on this drug and therefore it would be entirely inappropriate for anyone to take the drug for liver disease at present. We are hoping to start trials in the next year or so with the prospect of treatment perhaps five or six years off.
Hey Jim-Lactulose was given to my father, who had a stroke, for the purpose of a stool softner? It was used everday and certainly did the trick!
SJL
SJL
Orleans: His take was that the money it would take to study this existing, old and cheap drug just wasn't there.
------------------
Yes, now I somewhat remember the discussion. Thanks.
HR makes a good point about who is going to foot the bill to bring a drug to market that may not have enough profit potential.
------------------
Yes, now I somewhat remember the discussion. Thanks.
HR makes a good point about who is going to foot the bill to bring a drug to market that may not have enough profit potential.
I HAVEBEEN TAKING IT FOR ABOUT 7 MONTHS WITH NO SIDES OR OUTGOING DAMAGES-LIKE ALL DRUGS THERE COULD BE DAMAGES BUT AFTER 3 OPINIONS THIS DRUG IS SUPPOSED TO BE FAR SAFEST OF ALL ARTHIRITIS DRUGS AND YES IT IS SAID TO HALT FIBROSIS BUT I TAKE IT FOR ARTHIRIS- MY LEVELS WERE O.K. BUT NOW STOPPED TREATMENT FOR HEP BECAUSE OF AMINEA WHICH I AM TRYING TO CONTROL AND THEN BACK TO TREATMENT-W.S.
A cheap and readily available drug could reverse severe liver disease, even in patients who find it impossible to give up booze, research suggests.
AWESOME - JACK DANIELS HERE I COME!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! :) FINALLY!!!!!!!!!!!!!!! ;)
AWESOME - JACK DANIELS HERE I COME!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! :) FINALLY!!!!!!!!!!!!!!! ;)
there is also an interesting 2003 article: it provides a list of "candidate substances" which could have some beneficial effect on fibrosis and cirrhosis.
http://www.bmj.com/cgi/reprint/327/7407/143.pdf
http://www.bmj.com/cgi/reprint/327/7407/143.pdf
this is old news i remember reading about this some time ago on the UK forum. i wish we would hear more about it, sure would be great news to say the least.
Hey, Yes this was disscussed several months ago. I ran across this article and raised it on this forum. HR said that it had been talked about BEFORE then. (jmjm, you were in on this if I remember correctly) His take was that the money it would take to study this existing, old and cheap drug just wasn't there. The BBC ariticle stated that these guys were planning to work on this approach (Mann and Day were thier names I think). I have searched several times but have found nothing. w.s./ So what is your story? How long have you been taking it? How long with hep c? etc.? later,jm
i would think that with all the arthritic EHM that many face that his med may be RX and considered. however sulfasalazine does present possible undesirable side effects including medication induced hepatitis. labs must be monitored for serum levels and perhaps with liver enzymes if this med would be considered by clinicians.
i believe we all should challenge our docs to consider anti fibrotic therapies besides all the usual good living practices that we have all come to know and cherish. it is definitely another goal to be won in this disease.
i believe we all should challenge our docs to consider anti fibrotic therapies besides all the usual good living practices that we have all come to know and cherish. it is definitely another goal to be won in this disease.
I HAVE HEP C AND ALSO SIRITHIC ARTHIRITIS- I TAKE SALSAMINE ALSO- IT HAS BEEN USED FOR ARTHIRITIS FOR MANY YEARS- THE REASON I TAKE IT IS BECAUSE IT IS THE SAFEST LIVER FRIENDLY ARTHIRITIS DRUG AVAILABLE-HOWEVER I HAVE READ AN ARTICLE IN HEP MAGAZINE THAT THEY STATED THAT ITWILL HELP WITH CIRROUSIS- HOWEVER THEY SAY COFFEE IS ALSO-THIS IS NOT PROBLY EVER GOING TO BE USED FOR CIRROUSIS CURE AS IT IS PRIMARLY A ARTHIRITIS DRUG-W.S.
Wow, that drug sounds great! I hope it's still be studied and hopefully moved forward so, if all goes well, it can be available for humans ASAP. It does seem amazingly simplistic, doesn't it... but sometimes the most effective solutions are not the most complicated. Let's hope that's the case here!
-Dee
-Dee
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