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Sofusbuvir hep c
Who says sofosbuvir costs $90,000. Gilead sciences will cry if they come India and see it being sold at just $200/28 tabs. If anyone want to get it don't look here or there and come straight to India. Today I saw it and got shocked. Certainly if future drugs for hbv comes at unaffordable prices then not much time it will take indian companies will manufacture them at just .002% of the actual price. I don't know how are they allowed to make such patented drugs. This thing is good in context to poor patients but bad in context to research work coz drugs sold so cheap will make the profit and hardwork of researchers wane. It is a risk for hbv research also.
Ok got that. Probably reading microbiology and molecular mechanism for hep b will give some new infos
you are wrong and stephen is right. hbsag Antibodies once present at high concentrations can indeed enter liver cells. it is not really known how they enter liver cells and what exactly is the effect inside, but they seem to be able to contribute to a reduction in virion secretion. To know these kind of details you have to participate every year in the meeting on the molecular biology of hepatitis b viruses. Liver meetings will not cover that.
Very Nice and vivid explanation Stephen. Just one thing I want to say that antibodies can't enter cells (u said hbsab can enter liver cells) and work against only antigens in blood that's y they are called humoral immune system. Very right they are produced by B cells.
Regarding IFN gamma I ve heard/read that they are under trials and planned to be prepared commercially. This is wat update I was asking for.
Regarding IFN gamma I ve heard/read that they are under trials and planned to be prepared commercially. This is wat update I was asking for.
During the immune Tolerance phase, maybe up to 100% of hepatocytes are infected. During the Immune Control phase, the % should be much lower as reflected by very low serum hbvdna and the low level of cccDNA in the whole liver.
After hbv infection, we believe hbsab are produced, but not in sufficient quantity to neutralise all the hbsag on SVP and Dane particles circulating in the blood. Hbsab only attach to hbsag, mainly in the blood. Hbsab are produced by the B cells, released into the blood
and can enter liver cells. You should read up on the concept of antigen and antibody.
cccDNA is a minichromosome and not integrated with the human genomes. Fragments of cccDNA may be integrated into a human chromosome. But fragments are insufficient to replicate a new Dane particle.
There are many factors that make hbv speciat cd8+ cells exhausted or depleted, one of them is the excessive hbv viral antigens in the blood and within the liver. So low hbvdna, hbsag, hbeag in the blood all contribute to recovery of these T cells and their effector functions.
Interferon gamma is secreted by the cd8+ T cells. Nothing to update, you are confusing it with other types of interferon.
After hbv infection, we believe hbsab are produced, but not in sufficient quantity to neutralise all the hbsag on SVP and Dane particles circulating in the blood. Hbsab only attach to hbsag, mainly in the blood. Hbsab are produced by the B cells, released into the blood
and can enter liver cells. You should read up on the concept of antigen and antibody.
cccDNA is a minichromosome and not integrated with the human genomes. Fragments of cccDNA may be integrated into a human chromosome. But fragments are insufficient to replicate a new Dane particle.
There are many factors that make hbv speciat cd8+ cells exhausted or depleted, one of them is the excessive hbv viral antigens in the blood and within the liver. So low hbvdna, hbsag, hbeag in the blood all contribute to recovery of these T cells and their effector functions.
Interferon gamma is secreted by the cd8+ T cells. Nothing to update, you are confusing it with other types of interferon.
"What is the percentage of infected hepatocytes in a chronic hbv patient? "
"Generating antibodies against hbsag are not just sufficient."
These two questions not very clear.
Answer to the 2nd question is probably antibodies can only suppress hbsag not hbv dna. However suppression of hbsag alone won't activate cytotoxic cd8 activity to eliminate significant cccdna already integrated. Though immune activity will increase but dna elimination won't be possible by just hbsab production which will work outside cells not inside.
3rd what's the update for IFN gamma? If any kindly share it.i think it's still under trials not sure though?
"Generating antibodies against hbsag are not just sufficient."
These two questions not very clear.
Answer to the 2nd question is probably antibodies can only suppress hbsag not hbv dna. However suppression of hbsag alone won't activate cytotoxic cd8 activity to eliminate significant cccdna already integrated. Though immune activity will increase but dna elimination won't be possible by just hbsab production which will work outside cells not inside.
3rd what's the update for IFN gamma? If any kindly share it.i think it's still under trials not sure though?
HCV is an RNA virus. After entering a liver cell, it resides in the cytoplasm of the cell, and not in the nucleus.Sofosbuvir inhibits the RNA polymerase that the hepatitis C virus uses to replicate its RNA. The cytoplasm is a much more hostile environment than that inside a nucleus, without successful replication, the HCV RNA will be degraded. So without replication, hcv will perish.
For HBV, a DNA virus, after entering a liver cell, its genetic material enters the safe haven of the nucleus where it resides in the form cccDNA. Using the cccDNA as a template, the liver cell transcribes mRNA of the various HBV proteins as well as pgRNA. These are released into the cytoplasm to be made into various HBV proteins and the pgRNA to be reverse-transcribed back to hbv DNA. Tenofovir is a reverse transcriptase inhibitor (NRTI), that inhibits reverse transcriptase. Therefore Tenofovir inhibits the replication of HBV DNA but not HBV's various proteins, such the s, e, c, and x proteins.
"What could eliminate the infected hepatocytes or cccdna?"
Interferon Gamma can degrade cccDNA inside hepatocytes without killing the cells. HBV specific Cytotoxic T cells can kill an infected liver cell, and NK cells can also kill any infected cells.
"What is the percentage of infected hepatocytes in a hbv patient? "
During acute infection, it can be up to 100%.
"Generating antibodies again hbsag are not just sufficient."
Because there are far more Sub Viral Particles and Dane Particles, both have HBsAg coat, than HBsAb.
"For a cure one will need to have heavy liver damage by the drug induction of immune system that might make him very sick and current interferon fails in producing that in max individuals."
Not true. HBV specific T cells can degrade cccDNA within an infected liver without killing the cell, it can also kill infected cells outright. Our Immune System is very sophisticated and have checks and balances. Interferon have due effects- stimulates ISG within an infected liver cells to express proteins that will inhibit hbv replication; it also modulates other immune cells and activities.
Hope I got it right.
For HBV, a DNA virus, after entering a liver cell, its genetic material enters the safe haven of the nucleus where it resides in the form cccDNA. Using the cccDNA as a template, the liver cell transcribes mRNA of the various HBV proteins as well as pgRNA. These are released into the cytoplasm to be made into various HBV proteins and the pgRNA to be reverse-transcribed back to hbv DNA. Tenofovir is a reverse transcriptase inhibitor (NRTI), that inhibits reverse transcriptase. Therefore Tenofovir inhibits the replication of HBV DNA but not HBV's various proteins, such the s, e, c, and x proteins.
"What could eliminate the infected hepatocytes or cccdna?"
Interferon Gamma can degrade cccDNA inside hepatocytes without killing the cells. HBV specific Cytotoxic T cells can kill an infected liver cell, and NK cells can also kill any infected cells.
"What is the percentage of infected hepatocytes in a hbv patient? "
During acute infection, it can be up to 100%.
"Generating antibodies again hbsag are not just sufficient."
Because there are far more Sub Viral Particles and Dane Particles, both have HBsAg coat, than HBsAb.
"For a cure one will need to have heavy liver damage by the drug induction of immune system that might make him very sick and current interferon fails in producing that in max individuals."
Not true. HBV specific T cells can degrade cccDNA within an infected liver without killing the cell, it can also kill infected cells outright. Our Immune System is very sophisticated and have checks and balances. Interferon have due effects- stimulates ISG within an infected liver cells to express proteins that will inhibit hbv replication; it also modulates other immune cells and activities.
Hope I got it right.
Really it's very tough to treat hbv. The drug sovaldi for hep c just inhibits hcv polymerase and cure happens unlike the tenofovir which similarly inhibits DNA polymerase but no cure. What cud eliminate the infected hepatocytes or cccdna? What is the percentage of infected hepatocytes in a hbv patient? Generating antibodies again hbsag are not just sufficient. For a cure one will need to have heavy liver damage by the drug induction of immune system that might make him very sick and current interferon fails in producing that in max individuals. Sovaldi is a simple principle drug. Cure for hbv is not that close as it started looking to b. Can ever cd8 activity be evoked in chronic hbvers?
Right Steff but researches at low expenditures are not possible coz u never know how long more is the journey to destination and u need more fuel. Once a way is complete then other ways are paved at lesser efforts and inputs.
What do you expect the prices of coming drugs for hbv?
What do you expect the prices of coming drugs for hbv?
They are the same
my opinion is less money in pharma research can only do good and generatemore competition
my opinion is less money in pharma research can only do good and generatemore competition
How r these drugs so cheap in India while expensive in us? Are they not exactly the same as in us. Impurity in compound? Similarly tenofovir is also cheap here.
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