Aa
Pegasys affect on immune system?
I was under the impression HCV meds suppressed the immune system. In the class today, the guy said interferon helps boost the immune system. I'm a little confused now. I even asked to make sure that's what he meant to say. He said the pegasys boosts the immune system so the riba can kill the virus. So which is it?
The other posters are correct.
Interferons are a group of naturally occurring proteins that form an essential part of the immune system. Interferons operate in two ways. Firstly, they hinder the replication process of the virus. Secondly, they enhance the body’s immune response. They hinder the replication process by binding to receptors that are present on nearly all cell types. By doing this they prevent a virus from entering the cell and replicating within it.
Interferons enhance the immune response by stimulating the activity of immune cells and rendering virus-infected cells more susceptible to the responses of the immune system. The three types of interferon are referred to by Greek letters - alpha, beta and gamma. In its naturally occurring form alpha interferon is produced by the body to fight infections, notably flu. It is responsible for many of the symptoms associated with flu, such as headaches, fever, and the shivers. As a treatment for hepatitis C, interferon is synthetically produced in a laboratory and administered by injection under the skin in very high doses. It is hardly surprising that some of the usual side effects of taking interferon are actually flu-like symptoms.
Ribavirin
Ribavirin is a synthetic antiviral nucleoside analogue. In the treatment of hepatitis C it works very successfully with interferon but not on its own. It was originally developed as an antiviral agent for diseases that cause respiratory problems.
The possibility for it being used in conjunction with interferon was first noted in 1990. Since 1998 it has been incorporated into standard treatment for hepatitis C. Ribavirin inhibits viral growth, has anti-viral properties and interrupts the way the hepatitis C virus absorbs genetic material when it replicates.
In the majority of cases, for the treatment of hepatitis C ribavirin is used alongside interferon. Ribavirin is ineffective against hepatitis C on its own. It comes in 200mg pill or capsule form and is taken orally, twice daily, with the dose being dependent on patient weight and genotype.
------------------------------------------------------------------------------------------
Treatment Failure and Resistance with Direct-Acting Antiviral Drugs Against Hepatitis C Virus
http://onlinelibrary.wiley.com/doi/10.1002/hep.24262/pdf
"HCV Clearance
In order to achieve an SVR, it is necessary (1) to shut down virus production and thereby to achieve a rapid initial decline in circulating HCV RNA;
(2) tomaintain viral inhibition throughout treatment; and
(3) to induce a significant, slower second phase of decline in HCV RNA, leading to gradual clearance of HCV-infected liver cells, through cell death or, more often, HCV removal.
A hypothesis is that restoration of the intracellular innate immune response by viral inhibition plays an important role in the clearance of residual HCV genomes from these cells. Both IFN-a and DAAs have potent antiviral properties and are able to induce a rapid first-phase decline in HCV RNA. Ribavirin addition enhances the second-phase decline induced by pegylated IFN-a, accelerating the clearance or cure of infected cells through unknown molecular mechanisms. Recent data may suggest that ribavirin could have the same effect when combined with DAAs.
An SVR can only be achieved if the second-phase decline is gradual and treatment lasts long enough to ensure that all infected cells are
cleared or cured. Otherwise, HCV replication resumes shortly after treatment completion and the patient experiences a clinical relapse. Hepatitis C treatment failure is defined as the failure to achieve an SVR, i.e. a failure to eradicate HCV from the patient.
Concepts in Resistance to DAAs
Most knowledge on viral resistance to antiviral drugs comes from experience with antiretrovirals. Recent reports show that the same concepts are applicable to other viruses, including hepatitis B virus and HCV. Viral resistance to a DAA corresponds to the selection, during treatment, of viral variants that bear amino acid substitutions altering the drug target, and that are therefore less susceptible to the drug’s inhibitory activity.
These drug-resistant variants preexist as minor populations within the patient’s quasispecies (the ensemble of all viral variant populations present in a given individual), as a result of the error-prone activity of the HCV RNA-dependent RNA polymerase
(RdRp), the large viral populations and the short halflife of the virus in peripheral blood.
Preexisting drug-resistant variants are rarely detected with current techniques prior to therapy, because the amino acid substitution(s) that confer resistance also generally reduce replicative capacity in the absence of the drug. More sensitive techniques, such as ultra-deep pyrosequencing, have been used to identify such resistant variants prior to treatment.
Drug exposure profoundly inhibits replication of the dominant, ‘‘wild-type’’ drug-sensitive viral population, and the resistant variants gradually occupy the vacant replication space. Partial resistance may allow a virus to replicate sufficiently for further mutations to accumulate, leading to stepwise decreases in drug susceptibility, albeit often at a cost of reduced replicative capacity. ‘‘Compensatory’’ or ‘‘secondary’’ mutations may restore the fitness of the resistant virus in vivo, allowing replication to reach near-baseline levels.
Resistance is usually associated with a typical ‘‘escape pattern’’, with rapid recovery of pretreatment levels of viral replication, when amino acid substitutions confer a high level of resistance without impairing fitness in the presence of the drug. Viral replication may resume more gradually if the resistant virus is not very fit. Antiviral efficacy in vivo may not be affected if a resistant variant naturally replicates at low levels and/or if the drug retains partial efficacy (particularly if drug exposure is high)."
Cheers!
Hector
Interferons are a group of naturally occurring proteins that form an essential part of the immune system. Interferons operate in two ways. Firstly, they hinder the replication process of the virus. Secondly, they enhance the body’s immune response. They hinder the replication process by binding to receptors that are present on nearly all cell types. By doing this they prevent a virus from entering the cell and replicating within it.
Interferons enhance the immune response by stimulating the activity of immune cells and rendering virus-infected cells more susceptible to the responses of the immune system. The three types of interferon are referred to by Greek letters - alpha, beta and gamma. In its naturally occurring form alpha interferon is produced by the body to fight infections, notably flu. It is responsible for many of the symptoms associated with flu, such as headaches, fever, and the shivers. As a treatment for hepatitis C, interferon is synthetically produced in a laboratory and administered by injection under the skin in very high doses. It is hardly surprising that some of the usual side effects of taking interferon are actually flu-like symptoms.
Ribavirin
Ribavirin is a synthetic antiviral nucleoside analogue. In the treatment of hepatitis C it works very successfully with interferon but not on its own. It was originally developed as an antiviral agent for diseases that cause respiratory problems.
The possibility for it being used in conjunction with interferon was first noted in 1990. Since 1998 it has been incorporated into standard treatment for hepatitis C. Ribavirin inhibits viral growth, has anti-viral properties and interrupts the way the hepatitis C virus absorbs genetic material when it replicates.
In the majority of cases, for the treatment of hepatitis C ribavirin is used alongside interferon. Ribavirin is ineffective against hepatitis C on its own. It comes in 200mg pill or capsule form and is taken orally, twice daily, with the dose being dependent on patient weight and genotype.
------------------------------------------------------------------------------------------
Treatment Failure and Resistance with Direct-Acting Antiviral Drugs Against Hepatitis C Virus
http://onlinelibrary.wiley.com/doi/10.1002/hep.24262/pdf
"HCV Clearance
In order to achieve an SVR, it is necessary (1) to shut down virus production and thereby to achieve a rapid initial decline in circulating HCV RNA;
(2) tomaintain viral inhibition throughout treatment; and
(3) to induce a significant, slower second phase of decline in HCV RNA, leading to gradual clearance of HCV-infected liver cells, through cell death or, more often, HCV removal.
A hypothesis is that restoration of the intracellular innate immune response by viral inhibition plays an important role in the clearance of residual HCV genomes from these cells. Both IFN-a and DAAs have potent antiviral properties and are able to induce a rapid first-phase decline in HCV RNA. Ribavirin addition enhances the second-phase decline induced by pegylated IFN-a, accelerating the clearance or cure of infected cells through unknown molecular mechanisms. Recent data may suggest that ribavirin could have the same effect when combined with DAAs.
An SVR can only be achieved if the second-phase decline is gradual and treatment lasts long enough to ensure that all infected cells are
cleared or cured. Otherwise, HCV replication resumes shortly after treatment completion and the patient experiences a clinical relapse. Hepatitis C treatment failure is defined as the failure to achieve an SVR, i.e. a failure to eradicate HCV from the patient.
Concepts in Resistance to DAAs
Most knowledge on viral resistance to antiviral drugs comes from experience with antiretrovirals. Recent reports show that the same concepts are applicable to other viruses, including hepatitis B virus and HCV. Viral resistance to a DAA corresponds to the selection, during treatment, of viral variants that bear amino acid substitutions altering the drug target, and that are therefore less susceptible to the drug’s inhibitory activity.
These drug-resistant variants preexist as minor populations within the patient’s quasispecies (the ensemble of all viral variant populations present in a given individual), as a result of the error-prone activity of the HCV RNA-dependent RNA polymerase
(RdRp), the large viral populations and the short halflife of the virus in peripheral blood.
Preexisting drug-resistant variants are rarely detected with current techniques prior to therapy, because the amino acid substitution(s) that confer resistance also generally reduce replicative capacity in the absence of the drug. More sensitive techniques, such as ultra-deep pyrosequencing, have been used to identify such resistant variants prior to treatment.
Drug exposure profoundly inhibits replication of the dominant, ‘‘wild-type’’ drug-sensitive viral population, and the resistant variants gradually occupy the vacant replication space. Partial resistance may allow a virus to replicate sufficiently for further mutations to accumulate, leading to stepwise decreases in drug susceptibility, albeit often at a cost of reduced replicative capacity. ‘‘Compensatory’’ or ‘‘secondary’’ mutations may restore the fitness of the resistant virus in vivo, allowing replication to reach near-baseline levels.
Resistance is usually associated with a typical ‘‘escape pattern’’, with rapid recovery of pretreatment levels of viral replication, when amino acid substitutions confer a high level of resistance without impairing fitness in the presence of the drug. Viral replication may resume more gradually if the resistant virus is not very fit. Antiviral efficacy in vivo may not be affected if a resistant variant naturally replicates at low levels and/or if the drug retains partial efficacy (particularly if drug exposure is high)."
Cheers!
Hector
It is my understanding that Interferon does not work on the HCV virus directly but rather indirectly through the induction of hundreds of Interferon Stimulating Genes which, in turn, inhibit viral protein, RNA synthesis. This produces an antiviral state rather than direct selection pressure that engenders mutations.
It is my understanding that Inc and Vic do not kill the HCV virus. They inhibit viral replication.
It is my understanding that Ribavirin works synergistically with Interferon although Ribavirins all inclusive role in HCV Tx still needs some clarity. Riba does enhance mutagenesis and plays a role in immune modulation.
Ribavirin has a role in penetrating protected compartments in that it is able to penetrate protected non-plasma compartments including extrahepatic compartments and and possibly cirrhotic nodules. It is important to know that Riba influences 2nd and NOT 1st phase of viral load decline.
This information is all from the presentations at the Am. Assoc. for the Study of Liver Diseases.
It is my understanding that Inc and Vic do not kill the HCV virus. They inhibit viral replication.
It is my understanding that Ribavirin works synergistically with Interferon although Ribavirins all inclusive role in HCV Tx still needs some clarity. Riba does enhance mutagenesis and plays a role in immune modulation.
Ribavirin has a role in penetrating protected compartments in that it is able to penetrate protected non-plasma compartments including extrahepatic compartments and and possibly cirrhotic nodules. It is important to know that Riba influences 2nd and NOT 1st phase of viral load decline.
This information is all from the presentations at the Am. Assoc. for the Study of Liver Diseases.
Interferon ramps up the immune system, sends it in overdrive to attack the virus. Ribavirin does not kill the virus, it inhibits the virus from replicating.
Victrelis and Incivek are direct acting antivirals. By design, they attack and kill the virus directly but must be used with interferon and ribavirin to effectively suppress the virus.
Victrelis and Incivek are direct acting antivirals. By design, they attack and kill the virus directly but must be used with interferon and ribavirin to effectively suppress the virus.
It boosts and that is why we get flu symptoms. When you are exposed to the flu virus your immune system goes into overdrive to attack and that is what makes us feel so bad when we get the flu. We are doing the same thing to fight the HCVirus.
At least that was how it was explained to me; you may get other and better info from others on here in awhile, I'm no expert. :)
At least that was how it was explained to me; you may get other and better info from others on here in awhile, I'm no expert. :)
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