Aa
Liver biopsy and relapse after treatment?
Is there any correlation between the two? Most of us have had biopsies before the start of treatment, who has relapsed after stopping treatment? I’m just curious about this and is there any research that may point in this direction?
Thanks!
jasper
Thanks!
jasper
Thanks, GREAT EXPLANATION. Now i see why extending tx is the way to go for difficult to tx pts. like myself. Ive heard it a thousand times that viral load doesnt really play a part , but this makes me wonder otherwise.
Ok I need to print this and study it a bit! But this is something I have wondered about for a awhile, speaks more clearly to me than some of the other things I have read.
I wish they would also do some more studies on relapse, I would volunteer for one!
Have a great weekend!
Deb
I wish they would also do some more studies on relapse, I would volunteer for one!
Have a great weekend!
Deb
The therapy is directed against and works by:
1. Eliminating Infected hepatocytes by CTL mediated killing / Eating the now dead hepatocytes pads
2. Noncytolytic elimination of the intracellular virus machinery by induction via CTL produced gamma IFN or therapeutically induced IFN alpha . Neutralizing of the central nerve system of the virion
3. Killing of hepatocytes, infected or not, by unspecific "bystander" inflammatory mechanisms caused by the unspecific proinflammatory capable of promoting inflammation, intrahepatic with in the liver, infiltrate and there the diffusion there of, ( In the biopsies seen as portal infiltrates and "necroinflammatory fibrosis and bridging " activity).
4. The prevention of reinfection by anti HCV antibodies binding to circulating virions is not of major importance in the dynamical fight of the immune system against HCV. For that reason hyperimmunserum hyper active immune response in the blood, "HCIG" CD4 binding ability, does not effectively prevent reinfection after transplantation. Currently, two companies are trying to develop a pair of strongly binding anti HCV monoclonals, alfa antibodies in the hope to improve upon this mechanism to prevent reinfection after transplantation. Transplantation BTW is the one moment in which the extrahepatic out side of the liver virons DO come into play, becuse they reinfect the new, vrgin liver .
Right, the circulating virions in the blood serum and extracellular fluids can only infect the uninfected hepatocyte pad of the liver. Yet, the floating virions circulating in the serum and extrecellular fluids are either dieing or dead on their own and triggers the “natural INF” response of CTL’s and helper T cells or killer cells that attacks the invader virions and or decaying virus cells, which is over come after the initial infection process begins and ongoing process. Thus reducing the viral load of the virions with in the liver caused by the induced therapy of the combo treatment but there are few who survive either because of their stronger (DNA) for lack of words, and or because of their thicker lipid coats makes and its way back to the liver through the serum to a virgin hepatocytes pads.
I also would be interested if there are any studies out there that may have explored if there was a connection between the biopsy and relapse. Maybe not but still interesting and may come out years from now.
jasper
1. Eliminating Infected hepatocytes by CTL mediated killing / Eating the now dead hepatocytes pads
2. Noncytolytic elimination of the intracellular virus machinery by induction via CTL produced gamma IFN or therapeutically induced IFN alpha . Neutralizing of the central nerve system of the virion
3. Killing of hepatocytes, infected or not, by unspecific "bystander" inflammatory mechanisms caused by the unspecific proinflammatory capable of promoting inflammation, intrahepatic with in the liver, infiltrate and there the diffusion there of, ( In the biopsies seen as portal infiltrates and "necroinflammatory fibrosis and bridging " activity).
4. The prevention of reinfection by anti HCV antibodies binding to circulating virions is not of major importance in the dynamical fight of the immune system against HCV. For that reason hyperimmunserum hyper active immune response in the blood, "HCIG" CD4 binding ability, does not effectively prevent reinfection after transplantation. Currently, two companies are trying to develop a pair of strongly binding anti HCV monoclonals, alfa antibodies in the hope to improve upon this mechanism to prevent reinfection after transplantation. Transplantation BTW is the one moment in which the extrahepatic out side of the liver virons DO come into play, becuse they reinfect the new, vrgin liver .
Right, the circulating virions in the blood serum and extracellular fluids can only infect the uninfected hepatocyte pad of the liver. Yet, the floating virions circulating in the serum and extrecellular fluids are either dieing or dead on their own and triggers the “natural INF” response of CTL’s and helper T cells or killer cells that attacks the invader virions and or decaying virus cells, which is over come after the initial infection process begins and ongoing process. Thus reducing the viral load of the virions with in the liver caused by the induced therapy of the combo treatment but there are few who survive either because of their stronger (DNA) for lack of words, and or because of their thicker lipid coats makes and its way back to the liver through the serum to a virgin hepatocytes pads.
I also would be interested if there are any studies out there that may have explored if there was a connection between the biopsy and relapse. Maybe not but still interesting and may come out years from now.
jasper
Well it would seem to me if a person had a biopsy that means taking tissue out of the liver and if you take tissue out of an organ will it bleed? Or if it hits an infected hepatocyte is there a whole left behind, and if so will the virus/virions escape into the interstitial fluids from it? I would think, yes virions or virus would go into the interstitial fluids and at a time of a high viral load with in the liver.
The reason why I had brought this up was a thread in which HR and I conversed in part about the sensitivity of the different blood test and had questioned him about floater virions, but let the thread go at the time but not forgotten. The exerts below will explain why I had asked the question.
HR - The 30% chance was only referring to the 1ml of serum investigated in the test. You could still have 3000 viruses in the non tested other part of the blood and also there will some be located in the interstitial fluid - outside of blood vessels but also out side of the bodys tissues. that is at least 10 more liters of fluid where a virus can be, although the concentrations in this interstitial space should be less than in the circulation, since the virus is at least partly confined/blocked off by the endothelium lining of blood vesels.
Note however that in the liver this otherwise fairly tight endothelial lining has numerous large holes (fenestrations) - to allow better access of plasma components to the liver cells, that actually for this reason come in direct contact with the plasma alongside the sinusoids, this way there is no barrier for viruses in the liver capillaries at all.
Getter - So, given both of these test and one down to 2iu and if there is a scarce remote possibility that even one lone virion has survived both test, and you still shows undetected in the 2 ml of blood sampled down to 2iu is there still a possibility or (error) rate that one virion has survived in the 2iu test and if the immune system is not fighting anything else it would seem that there would be a very good chance of remaining or obtaining SVR. But there is still that possibility that in a compromised immune system or even a healthy immune system, a one lone virion or virions in the other 3,998 milliliters of blood can still replicate when the trough is created by the sudden stopping of INF at the end of treatment, is there that possibility and giving hr’s 30% chance of no virus left there is still in reality a 70% chance there are in the other 3,998 ml of blood, am I reading all this right?
HR - The 30% chance was only referring to the 1ml of serum investigated in the test. You could still have 3000 viruses in the non tested other part of the blood and also there will some be located in the interstitial fluid - outside of blood vessels but also out side of the bodys tissues. that is at least 10 more liters of fluid where a virus can be, although the concentrations in this interstitial space should be less than in the circulation, since the virus is at least partly confined/blocked off by the endothelium lining of blood vesels.
Note however that in the liver this otherwise fairly tight endothelial lining has numerous large holes (fenestrations) - to allow better access of plasma components to the liver cells, that actually for this reason come in direct contact with the plasma alongside the sinusoids, this way there is no barrier for viruses in the liver capillaries at all.
Getter - So what has changed is, is in the initial up dosing of the combo it has or should have eradicated all most all of the virions in the first 12 weeks of TX for (responders speaking) as UND, and for the remainder of TX is for the remaining TX time is for the body compartments and or organ components in which the virus may or may not find their way back into the blood stream and this is why the post PCR are needed to see if any remaining virions have reentered the blood stream which leads us back to the taper down Theory, at least for me anyway.
HR - Surprisingly, the circulating or otherwise existing in the extracellular fluid virions are only of relevance insofar as they can reinfect new, uninfected hepatocytes , from the blood passing though the liver .
right
All virions that do not reinfect are of importance only insofar as they (or better their processed remnants, taken up by macrophages and dendritic cells.) act as a trigger to the peripheral immune system to produce cognate CTLs and helper T lymphocytes.
Attacking as a foreign invader and eat up any unused and decaying virus cells
The immune system and IFN or riba does not have any direct effect on circulating virions ( with the minor exemption in the case of HCVs minor neutralizing antibodies ) Killer Cells, nor would such an effect be of any importance in the fight against the infection , unless it would reduce the number of circulating virions to such numbers that reinfections could not occur anymore, (which is a very small number). Reduced viral load by eradicating the number of virions being produced in the liver which is where the cleaving mutilation occurs.
HR - There is really no "virus killing' going on outside of the liver (because of their lipid coats) in the sense of an active, therapy induced destruction. Because of their RNA make up, Circulating virions have a short life and die by themself in huge numbers, a small number only makes it back Stronger RNA life cycle and lipid coats, to the liver and finds a fresh hepatocyte to infect and to start a new virus producing intracellular machinery.
The reason why I had brought this up was a thread in which HR and I conversed in part about the sensitivity of the different blood test and had questioned him about floater virions, but let the thread go at the time but not forgotten. The exerts below will explain why I had asked the question.
HR - The 30% chance was only referring to the 1ml of serum investigated in the test. You could still have 3000 viruses in the non tested other part of the blood and also there will some be located in the interstitial fluid - outside of blood vessels but also out side of the bodys tissues. that is at least 10 more liters of fluid where a virus can be, although the concentrations in this interstitial space should be less than in the circulation, since the virus is at least partly confined/blocked off by the endothelium lining of blood vesels.
Note however that in the liver this otherwise fairly tight endothelial lining has numerous large holes (fenestrations) - to allow better access of plasma components to the liver cells, that actually for this reason come in direct contact with the plasma alongside the sinusoids, this way there is no barrier for viruses in the liver capillaries at all.
Getter - So, given both of these test and one down to 2iu and if there is a scarce remote possibility that even one lone virion has survived both test, and you still shows undetected in the 2 ml of blood sampled down to 2iu is there still a possibility or (error) rate that one virion has survived in the 2iu test and if the immune system is not fighting anything else it would seem that there would be a very good chance of remaining or obtaining SVR. But there is still that possibility that in a compromised immune system or even a healthy immune system, a one lone virion or virions in the other 3,998 milliliters of blood can still replicate when the trough is created by the sudden stopping of INF at the end of treatment, is there that possibility and giving hr’s 30% chance of no virus left there is still in reality a 70% chance there are in the other 3,998 ml of blood, am I reading all this right?
HR - The 30% chance was only referring to the 1ml of serum investigated in the test. You could still have 3000 viruses in the non tested other part of the blood and also there will some be located in the interstitial fluid - outside of blood vessels but also out side of the bodys tissues. that is at least 10 more liters of fluid where a virus can be, although the concentrations in this interstitial space should be less than in the circulation, since the virus is at least partly confined/blocked off by the endothelium lining of blood vesels.
Note however that in the liver this otherwise fairly tight endothelial lining has numerous large holes (fenestrations) - to allow better access of plasma components to the liver cells, that actually for this reason come in direct contact with the plasma alongside the sinusoids, this way there is no barrier for viruses in the liver capillaries at all.
Getter - So what has changed is, is in the initial up dosing of the combo it has or should have eradicated all most all of the virions in the first 12 weeks of TX for (responders speaking) as UND, and for the remainder of TX is for the remaining TX time is for the body compartments and or organ components in which the virus may or may not find their way back into the blood stream and this is why the post PCR are needed to see if any remaining virions have reentered the blood stream which leads us back to the taper down Theory, at least for me anyway.
HR - Surprisingly, the circulating or otherwise existing in the extracellular fluid virions are only of relevance insofar as they can reinfect new, uninfected hepatocytes , from the blood passing though the liver .
right
All virions that do not reinfect are of importance only insofar as they (or better their processed remnants, taken up by macrophages and dendritic cells.) act as a trigger to the peripheral immune system to produce cognate CTLs and helper T lymphocytes.
Attacking as a foreign invader and eat up any unused and decaying virus cells
The immune system and IFN or riba does not have any direct effect on circulating virions ( with the minor exemption in the case of HCVs minor neutralizing antibodies ) Killer Cells, nor would such an effect be of any importance in the fight against the infection , unless it would reduce the number of circulating virions to such numbers that reinfections could not occur anymore, (which is a very small number). Reduced viral load by eradicating the number of virions being produced in the liver which is where the cleaving mutilation occurs.
HR - There is really no "virus killing' going on outside of the liver (because of their lipid coats) in the sense of an active, therapy induced destruction. Because of their RNA make up, Circulating virions have a short life and die by themself in huge numbers, a small number only makes it back Stronger RNA life cycle and lipid coats, to the liver and finds a fresh hepatocyte to infect and to start a new virus producing intracellular machinery.
Was looking for that word the other day, got stuck on antibodies, thanks!
This is something I am really interested in, I think they do can and do hang out sometimes. dormant. Then something wakes them up.
I have no proof though, would love to read more about this!
Deb
This is something I am really interested in, I think they do can and do hang out sometimes. dormant. Then something wakes them up.
I have no proof though, would love to read more about this!
Deb
I have also had a biopsy before starting treatment and after reading about intercellular virions in the body compartments, was just wondering if the 3000 or more virions that are floating around in the body fluids may have been attributed to the biopsy?
Jasper
Jasper
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