Aa
Houston, this is 13...
I am beginning to think about my end of treatment plan and looking for thoughts on the subject. HR has discussed the tapering topic in the past.....
by HR
"It needs to be understood that when stopping IFN, a new form of antiviral defense against possible HCV remnants needs to take hold and establish itself - the adaptive Tcell response, that up to this point was greatly aided by the direct effect of IFN on the hepatocytes and the local intrahepatic immune cells. With this IFN aid gone all the burden is on the Tcell response, that will typically get stronger if more remnant viruses are seen ( if they can be seen now, because new epitopes are now present) - with incredible sensitivity, but it takes time to come to full swing and it can furthermore, at this very critical moment, be paralyzed by the prominent absence of innate signals needed to get adaptive Tcell responses going after IFN is abruptly missing from the equation. Here is one more specific EXAMPLE how the Tcell effect depends on the presence of some Interferon: The presentation of the viral epitopes is performed - as described in detail in an earlier post- by the cellular proteasome and the class I MHC molecules that bind the peptide and bring it to the surface for recognition by the "cognate" Tcell receptors of the "cognate" Tcell patrolling the liver."
He also recommended adding Lactoferrin at this time to help the immune system come "back online". Has anyone tried this? And any opinions on other immune enhancing supplements? Thanks.
---------------------------
"Houston, we need to go over those re-entry procedures so there are no foul ups, so here is what you are going to do, give us whatever you got so we can look em over. We are all a bit tired up here... and the earths getting awfully big in the window...."
"13... this is Houston, we are going to get those procedures to you just as soon as we possibly can. Ken Mattingly is in the simulator as we speak..."
"Roger that Houston... Kens working on it..."
by HR
"It needs to be understood that when stopping IFN, a new form of antiviral defense against possible HCV remnants needs to take hold and establish itself - the adaptive Tcell response, that up to this point was greatly aided by the direct effect of IFN on the hepatocytes and the local intrahepatic immune cells. With this IFN aid gone all the burden is on the Tcell response, that will typically get stronger if more remnant viruses are seen ( if they can be seen now, because new epitopes are now present) - with incredible sensitivity, but it takes time to come to full swing and it can furthermore, at this very critical moment, be paralyzed by the prominent absence of innate signals needed to get adaptive Tcell responses going after IFN is abruptly missing from the equation. Here is one more specific EXAMPLE how the Tcell effect depends on the presence of some Interferon: The presentation of the viral epitopes is performed - as described in detail in an earlier post- by the cellular proteasome and the class I MHC molecules that bind the peptide and bring it to the surface for recognition by the "cognate" Tcell receptors of the "cognate" Tcell patrolling the liver."
He also recommended adding Lactoferrin at this time to help the immune system come "back online". Has anyone tried this? And any opinions on other immune enhancing supplements? Thanks.
---------------------------
"Houston, we need to go over those re-entry procedures so there are no foul ups, so here is what you are going to do, give us whatever you got so we can look em over. We are all a bit tired up here... and the earths getting awfully big in the window...."
"13... this is Houston, we are going to get those procedures to you just as soon as we possibly can. Ken Mattingly is in the simulator as we speak..."
"Roger that Houston... Kens working on it..."
CA: The study (Schiffman) you refering to is 12 years old and it was with the old interferon (not pegulated) its make me wonder why Schiffman hasn´t continued trapping down now 12 years later when treating patience, if it really was something in this trapping down theori.
--------
Not having the full-text but based on the abstract --
Not only was the interferon not Pegalayted, but no ribavirin may have been used. Also, note that the non-taper group was only treated for SIX MONTHS and I'm assuming it had it's share of genotype 1's. The "taper" group was treated TWELVE months if you take into account the six monthly taper periods.
The only thing this study seems to prove is that a longer period of interferon treatment benefited the so-called "taper" group. The study may even suggeat that lower-doses of interferon should be investigated for months 6-12 instead of full-dose. What it does not prove at face value is that tapering interferon has any benefit.
And yes, if this study had legs to carry over to modern treatment protocols, I assume Shiffman would be advocating tapering which to my knowledge he doesn't.
Link to study abstract: http://www.ncbi.nlm.nih.gov/pubmed/8707264
-- Jim
--------
Not having the full-text but based on the abstract --
Not only was the interferon not Pegalayted, but no ribavirin may have been used. Also, note that the non-taper group was only treated for SIX MONTHS and I'm assuming it had it's share of genotype 1's. The "taper" group was treated TWELVE months if you take into account the six monthly taper periods.
The only thing this study seems to prove is that a longer period of interferon treatment benefited the so-called "taper" group. The study may even suggeat that lower-doses of interferon should be investigated for months 6-12 instead of full-dose. What it does not prove at face value is that tapering interferon has any benefit.
And yes, if this study had legs to carry over to modern treatment protocols, I assume Shiffman would be advocating tapering which to my knowledge he doesn't.
Link to study abstract: http://www.ncbi.nlm.nih.gov/pubmed/8707264
-- Jim
Dr. Dieterich addressed the tapering issue in our Expert Forum so time back.
Essentialy, what he said is that there's no reason to taper since there's a natural taper built into both the Peg and riba, being their half life.
So in effect, what you and HR are talking about is extending the taper.
As to extending the taper, this concept does not seem to address what I believe were HR's concerns regarding what might be termed a low immune "window" right after the drugs are stopped when he proposed the virus might rebound.
It would seem to me that the during this window the natural taper would protect such a rebound from happening should that window/rebound theory be correct.
Also keep in mind that around 90% of all relapses occur within 30 days of stopping the peg -- again, a period that should be covered by the natural taper of Peg, i.e. stopping all the Peg at once.
Lastly, if you do want to taper, the taper should be at the end of the pre-determined course of treatment -- i.e. as an add-on -- as opposed to shortening the full course because of the taper.
-- Jim
Essentialy, what he said is that there's no reason to taper since there's a natural taper built into both the Peg and riba, being their half life.
So in effect, what you and HR are talking about is extending the taper.
As to extending the taper, this concept does not seem to address what I believe were HR's concerns regarding what might be termed a low immune "window" right after the drugs are stopped when he proposed the virus might rebound.
It would seem to me that the during this window the natural taper would protect such a rebound from happening should that window/rebound theory be correct.
Also keep in mind that around 90% of all relapses occur within 30 days of stopping the peg -- again, a period that should be covered by the natural taper of Peg, i.e. stopping all the Peg at once.
Lastly, if you do want to taper, the taper should be at the end of the pre-determined course of treatment -- i.e. as an add-on -- as opposed to shortening the full course because of the taper.
-- Jim
Was talking some swenglish here i mean tapering when said trapping in swedisk trappa means stair so the correct translation would have been staring down like walking downstaiers a little bit of the time instead of jumping down all the stairs at once.
The study (Schiffman) you refering to is 12 years old and it was with the old interferon (not pegulated) its make me wonder why Schiffman hasn´t continued trapping down now 12 years later when treating patience, if it really was something in this trapping down theori.
And I think we should all bear in mind that HR is not and never has treaten any HCV patient. I could be missinformed here both about Schiffman and HR please anyone correct me if I´m wrong.
Gauf if you have any fresher studys articles or other information that support (prove) the trapping down aproach please write in.
ca
ps. the fact can very well be that the people trapping down might just as well got the better SVR nr because they needed a little extra extending tx
And I think we should all bear in mind that HR is not and never has treaten any HCV patient. I could be missinformed here both about Schiffman and HR please anyone correct me if I´m wrong.
Gauf if you have any fresher studys articles or other information that support (prove) the trapping down aproach please write in.
ca
ps. the fact can very well be that the people trapping down might just as well got the better SVR nr because they needed a little extra extending tx
I agree that the tapering should be done AFTER the full soc treatment timeline. here is a copy of a study on the subject...
"Hepatology. 1996 Jul;24(1):21-6.
Improved sustained response following treatment of chronic hepatitis C by gradual
reduction in the interferon dose.
Shiffman ML, Hofmann CM, Luketic VA, Sanyal AJ, Contos MJ, Mills AS.
Hepatology Section, Medical College of Virginia, Richmond, Va 23298, USA.
Interferon (IFN) treatment of chronic hepatitis C virus (HCV) is associated with
a high rate of relapse. IFN is thought to exert its effect against HCV via direct
viral inhibition and immune stimulation. We have hypothesized that relapse
following termination of therapy results from the sudden withdrawal of this
immune modulatory effect and that gradual reduction in the IFN dose may decrease
the incidence of relapse. One hundred six patients with chronic HCV were enrolled
into this 24-month controlled, randomized prospective trial. All were treated
with 5 mU of interferon-alpha-2b three times a week for 6 months. Patients who
achieved biochemical response were randomized to either stop or taper IFN
gradually at monthly intervals as follows; 3 mu, 2 mU, 1 mU, and 0.5 mU (all
three times a week). 0.5 mU twice weekly and then once weekly. Liver histology
was assessed by Knodell index and HCV RNA was measured by a quantitative
polymerase chain reaction (PCR) assay. Of the 92 patients who completed the
initial 6 months of IFN treatment, 47 (51%) achieved biochemical response.
Twenty-one of these patients were randomized to stop IFN treatment and 25 to
taper (1 drop-out). At randomization patients were well matched with respect to
age, sex, race, serum alanine transaminase (ALT), and liver histology.
Biochemical relapse was observed in 19 of 21 (91%) patients who stopped IFN
treatment compared with only 60% who tapered IFN (P= .04).
Virological relapse
occurred in 90% of patients who stopped and only 48% of persons who tapered IFN
therapy.
At completion of the 24-month study patients who achieved long-term
sustained biochemical response had a significantly lower mean Knodell score (3.5
vs. 6.5) and a significantly greater number were HCV RNA negative in serum (85%
vs. 18%) compared with relapsers.
We conclude that gradual reduction in IFN dose
is associated with a SIGNIFICANT HIGHER RATE OF SUSTAINED RESPONSE and clearance
of HCV RNA from serum compared with abruptly stopping treatment. This in turn is
associated with a significant improvement in hepatic histology supporting the
premise that response to IFN therapy can prevent progression to cirrhosis. "
--------------------------------
More from HR
IFN has a strong influence on the intensity of expression - the number of proteins produced per cell - of the MHC class I proteins. Less IFN - less MHC, less presentations- less recognition - less killing of remnant virus infected cells, less general intrahepatic antiviral milieu by the gammaIFN secretion of these Tcells....
If you abruptly stop the enormous whipping up of the hepatocyte MHC production it will likely go into lower than normal mode for a while being so used to the whip...thus temporarily HCV remnants become invisible to the Tcell system.
If you taper AFTER the end of the full standardized tx period, then you will never have to ask yourself in case you still relapse, if it was the premature tapering that caused it. Tapering in this fashion can certainly cause no propensity for relapse, rather the opposite. Then at least you have done all you could under the circumstances.
What type of tapering schedule?
Each week one half of the previous dose would get you down in a "geometrical" fashion, as opposed to a linear one. 16mcg 8 4 2 1 1/2 1/4 1/8 Stop.
From patients reporting the "feel" of tapering down, each reduction feels quite good. As a matter of fact, some who stopped abruptly reported negative side effects from the counterswings of the system used to all that IFN. The point is, that tapering is not a useless extension of tx sides, but rather a gentle readjustment of the complex immune regulatory pathways directly or indirectly depending on IFN.
"Hepatology. 1996 Jul;24(1):21-6.
Improved sustained response following treatment of chronic hepatitis C by gradual
reduction in the interferon dose.
Shiffman ML, Hofmann CM, Luketic VA, Sanyal AJ, Contos MJ, Mills AS.
Hepatology Section, Medical College of Virginia, Richmond, Va 23298, USA.
Interferon (IFN) treatment of chronic hepatitis C virus (HCV) is associated with
a high rate of relapse. IFN is thought to exert its effect against HCV via direct
viral inhibition and immune stimulation. We have hypothesized that relapse
following termination of therapy results from the sudden withdrawal of this
immune modulatory effect and that gradual reduction in the IFN dose may decrease
the incidence of relapse. One hundred six patients with chronic HCV were enrolled
into this 24-month controlled, randomized prospective trial. All were treated
with 5 mU of interferon-alpha-2b three times a week for 6 months. Patients who
achieved biochemical response were randomized to either stop or taper IFN
gradually at monthly intervals as follows; 3 mu, 2 mU, 1 mU, and 0.5 mU (all
three times a week). 0.5 mU twice weekly and then once weekly. Liver histology
was assessed by Knodell index and HCV RNA was measured by a quantitative
polymerase chain reaction (PCR) assay. Of the 92 patients who completed the
initial 6 months of IFN treatment, 47 (51%) achieved biochemical response.
Twenty-one of these patients were randomized to stop IFN treatment and 25 to
taper (1 drop-out). At randomization patients were well matched with respect to
age, sex, race, serum alanine transaminase (ALT), and liver histology.
Biochemical relapse was observed in 19 of 21 (91%) patients who stopped IFN
treatment compared with only 60% who tapered IFN (P= .04).
Virological relapse
occurred in 90% of patients who stopped and only 48% of persons who tapered IFN
therapy.
At completion of the 24-month study patients who achieved long-term
sustained biochemical response had a significantly lower mean Knodell score (3.5
vs. 6.5) and a significantly greater number were HCV RNA negative in serum (85%
vs. 18%) compared with relapsers.
We conclude that gradual reduction in IFN dose
is associated with a SIGNIFICANT HIGHER RATE OF SUSTAINED RESPONSE and clearance
of HCV RNA from serum compared with abruptly stopping treatment. This in turn is
associated with a significant improvement in hepatic histology supporting the
premise that response to IFN therapy can prevent progression to cirrhosis. "
--------------------------------
More from HR
IFN has a strong influence on the intensity of expression - the number of proteins produced per cell - of the MHC class I proteins. Less IFN - less MHC, less presentations- less recognition - less killing of remnant virus infected cells, less general intrahepatic antiviral milieu by the gammaIFN secretion of these Tcells....
If you abruptly stop the enormous whipping up of the hepatocyte MHC production it will likely go into lower than normal mode for a while being so used to the whip...thus temporarily HCV remnants become invisible to the Tcell system.
If you taper AFTER the end of the full standardized tx period, then you will never have to ask yourself in case you still relapse, if it was the premature tapering that caused it. Tapering in this fashion can certainly cause no propensity for relapse, rather the opposite. Then at least you have done all you could under the circumstances.
What type of tapering schedule?
Each week one half of the previous dose would get you down in a "geometrical" fashion, as opposed to a linear one. 16mcg 8 4 2 1 1/2 1/4 1/8 Stop.
From patients reporting the "feel" of tapering down, each reduction feels quite good. As a matter of fact, some who stopped abruptly reported negative side effects from the counterswings of the system used to all that IFN. The point is, that tapering is not a useless extension of tx sides, but rather a gentle readjustment of the complex immune regulatory pathways directly or indirectly depending on IFN.
Have an Answer?
You are reading content posted in the Hepatitis C Community
Learn about this treatable virus.
Getting tested for this viral infection.
3 key steps to getting on treatment.
4 steps to getting on therapy.
What you need to know about Hep C drugs.
How the drugs might affect you.
These tips may up your chances of a cure.
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
