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Questions about Hepatitis C in General
Please correct my understanding if it’s wrong.
When the virus gets into the body the only place they can replicate themselves is liver.
So, when they get to the liver. They will get into the cell, and there shall be more virons coming out.
The real problem is WBC will attack liver cells that inflicted by virus.
After WBC attacks, liver will try to fix itself which will result in fibrosis.
When this repeated for decades, fibrosis will turn into cirrhosis.
First question,
Is my understanding correct?
Second question,
Why WBC cannot kill HepC virus?
Is it because it just is capable of doing that, or the virus replicates way too fast than WBC can kill?
If it really cannot kill, why injecting Pegylated Interferon will change the capability?
Third question,
Will the cell that virus got in die if it’s not attacked by WBC?
When the virus gets into the body the only place they can replicate themselves is liver.
So, when they get to the liver. They will get into the cell, and there shall be more virons coming out.
The real problem is WBC will attack liver cells that inflicted by virus.
After WBC attacks, liver will try to fix itself which will result in fibrosis.
When this repeated for decades, fibrosis will turn into cirrhosis.
First question,
Is my understanding correct?
Second question,
Why WBC cannot kill HepC virus?
Is it because it just is capable of doing that, or the virus replicates way too fast than WBC can kill?
If it really cannot kill, why injecting Pegylated Interferon will change the capability?
Third question,
Will the cell that virus got in die if it’s not attacked by WBC?
But we also know that VL can vary greatly, even day to day. So how does that figure in?
Thanks for sharing the synopsis Mike. My eyes also glazed over on the previous version, thinking I'd read it later tonight -- about a dozen times. :o)
This is the way I understand it - in layman's terms.
The primary mechanism of HCV induced liver damage is immune system related. Our immune system sees the invader Hepatitis C in the liver cells and begins to mount an attack. The article I posted above attempts to describe the details of the immune response but I don't think it is necessary to know the specifics to understand the basic process. I have been told by a liver transplant surgeon (I have never verified his complete analysis) that when the immune system attacks the HCV infected cells there can be collateral damage where uninfected cells as well as infected cells are targeted and attacked. Now, I have also read that the the Hep C virus itself can be cytopathic although the stuff I read suggests that this is not the primary mechanism of liver injury attributed to HCV. That article stated that immune mediated injury is the primary mechanism of liver damage but that there also seems to be a less significant cytopathic injury.
One of the first things we learn when we begin studying HCV is that Viral Load doesn't correlate with liver damage. That significant liver damage can exist in a patient with a low viral load and likewise patients with a high viral load can sometimes have little or no histological damage. That suggests strongly that since the viral load doesn't correlate with liver damage that it is not the cytopathic aspect of the virus that is the main cause of the liver damage. It is the immune response to the infection, in my opinion. It occurs to me that if the immune system ignores the HCV infection there might be little or no liver damage. The virus itself can't do much harm because, if it could, then we'd see a strong correlation with viral load and liver damage. Now, if the immune system mounts an aggressive and an effective attack we might expect to see spontaneous clearance. But, if the immune system mounts an aggressive but ineffective campaign we might see histological damage.
I theorized this last point and I could be all wrong. It's just my way of visualizing the process.
Mike
Mike
The primary mechanism of HCV induced liver damage is immune system related. Our immune system sees the invader Hepatitis C in the liver cells and begins to mount an attack. The article I posted above attempts to describe the details of the immune response but I don't think it is necessary to know the specifics to understand the basic process. I have been told by a liver transplant surgeon (I have never verified his complete analysis) that when the immune system attacks the HCV infected cells there can be collateral damage where uninfected cells as well as infected cells are targeted and attacked. Now, I have also read that the the Hep C virus itself can be cytopathic although the stuff I read suggests that this is not the primary mechanism of liver injury attributed to HCV. That article stated that immune mediated injury is the primary mechanism of liver damage but that there also seems to be a less significant cytopathic injury.
One of the first things we learn when we begin studying HCV is that Viral Load doesn't correlate with liver damage. That significant liver damage can exist in a patient with a low viral load and likewise patients with a high viral load can sometimes have little or no histological damage. That suggests strongly that since the viral load doesn't correlate with liver damage that it is not the cytopathic aspect of the virus that is the main cause of the liver damage. It is the immune response to the infection, in my opinion. It occurs to me that if the immune system ignores the HCV infection there might be little or no liver damage. The virus itself can't do much harm because, if it could, then we'd see a strong correlation with viral load and liver damage. Now, if the immune system mounts an aggressive and an effective attack we might expect to see spontaneous clearance. But, if the immune system mounts an aggressive but ineffective campaign we might see histological damage.
I theorized this last point and I could be all wrong. It's just my way of visualizing the process.
Mike
Mike
LOL we all must look the same out here stumbling and bumbling with our glassy eyes going "what is your name?, what is your name?"
All except the Mr. Smarty Pantses that is, thank God for their ability to sum things up for us Silly Girls :)
All except the Mr. Smarty Pantses that is, thank God for their ability to sum things up for us Silly Girls :)
I need the paramedic talking to a barely conscious person version. :p WHAT'S YOUR NAME? DO YOU KNOW WHAT YEAR IT IS?
The way I see it is this is an odd virus, which affects different people in different ways. Some people have hcv for decades with no damage while others get cirrhosis.
I don't know why, don't need to know why, I just know that's how it is and accept it as such.
There's still so much unknown about hcv.
Mikesimon is the king of digging up incredible research but for me,unless it's in layman's terms, my eyes get kind of glossy.
I don't know why, don't need to know why, I just know that's how it is and accept it as such.
There's still so much unknown about hcv.
Mikesimon is the king of digging up incredible research but for me,unless it's in layman's terms, my eyes get kind of glossy.
LOL that's what I really like about you Suezee you are just like me - but at least we admit what we don't know! I need the one sentence abridged slow persons version...then I'm good!
http://www.hawaii.edu/hivandaids/Fibrosis%20And%20Disease%20Progression%20In%20Hepatitis%20C.pdf
"when your immune system attacks an invaded liver cell, it kills the cell, resulting in scarring. enough of that leads to fibrosis, more of that leads to cirrhosis."
This is confusing to me. Just last week I spoke with my hepatologist about the reasons I have little liver damage despite having been infected by HCV (estimate) almost 30 years ago. My liver enzymes have never been outside the 'normal range' either. Having type 1 diabetes I have complete blood work done every 6 months including cholesterol and liver enzymes.
I said that I don't drink, eat well and exercise and attributed my 'healthy' liver to that. He said no, I have my immune system to thank for keeping my liver healthy.
Are you saying that the immune system somehow "kills the cell"? I'm confused. Can you site a source for this information?
This is confusing to me. Just last week I spoke with my hepatologist about the reasons I have little liver damage despite having been infected by HCV (estimate) almost 30 years ago. My liver enzymes have never been outside the 'normal range' either. Having type 1 diabetes I have complete blood work done every 6 months including cholesterol and liver enzymes.
I said that I don't drink, eat well and exercise and attributed my 'healthy' liver to that. He said no, I have my immune system to thank for keeping my liver healthy.
Are you saying that the immune system somehow "kills the cell"? I'm confused. Can you site a source for this information?
Great information, every day I learn another thing on here. So easy to say it replicates in the liver blah blah blah - but considering scientists aren't even sure of the entire process, I guess that would be incorrect information wouldn't it?
Thx. for the article Mike ..just not quite as simple as some of the explanations I read sometimes by those not in the medical commnity.
Will
http://ajpgi.physiology.org/content/290/5/G847.long
As mentioned, HCV infection frequently leads to severe liver diseases including liver cirrhosis and HCC. The molecular mechanism of HCV pathogenesis remains unclear. Lipid peroxidation products are increased in serum, peripheral blood mononuclear cells (PBMC), and liver specimen from hepatitis C patients. 4-Hydroxynonenal (HNE) and 8-hydroxyguanosine, a marker of oxidative DNA damage, are elevated (15). In addition, there is a significant reduction of hepatic, plasmatic, and lymphocytic GSH levels in patients chronically infected by HCV, particularly with the 1b genotype (15). The percentage of oxidized GSH (GSSG) was increased, suggesting an increased GSH turnover.
Will
http://ajpgi.physiology.org/content/290/5/G847.long
As mentioned, HCV infection frequently leads to severe liver diseases including liver cirrhosis and HCC. The molecular mechanism of HCV pathogenesis remains unclear. Lipid peroxidation products are increased in serum, peripheral blood mononuclear cells (PBMC), and liver specimen from hepatitis C patients. 4-Hydroxynonenal (HNE) and 8-hydroxyguanosine, a marker of oxidative DNA damage, are elevated (15). In addition, there is a significant reduction of hepatic, plasmatic, and lymphocytic GSH levels in patients chronically infected by HCV, particularly with the 1b genotype (15). The percentage of oxidized GSH (GSSG) was increased, suggesting an increased GSH turnover.
"Immune-Mediated Liver Damage
The exact mechanism by which hepatitis C virus (HCV) causes liver cell damage is unknown. High levels of HCV replication have been reported in both immunocompetent and immunosuppressed patients with little or no intrahepatic damage, including inflammation.[McGuinness 1996] Indeed, in patients receiving liver graft as a result of chronic hepatitis C, where HCV infection recurs in virtually all patients, ~ 30% of patients fail to develop recurrent hepatitis 1 year after transplantation despite high levels of HCV replication.[Demetris 2009] It appears as if the host immune system tolerates high levels of intrahepatic HCV replication without killing the infected cells. Putting these observations together, HCV-associated cell damage seems to be largely mediated by the host immune response. Indeed, the hallmark of liver damage associated with HCV infection is a lympho-mononuclear infiltrate mostly represented by CD8+ T cells that are thought to play a major role in viral containment, although other subsets can be detected, such as CD4+, natural killer, and especially regulatory T (Treg) cells.[Spengler 2007] Several investigators have indeed reported how intrahepatic CD4+ and CD8+ cells are specific for different structural and nonstructural HCV antigens.[Koziel 1992; Schirren 2000] Why this immune reaction cannot resolve the infection in most patients is unclear. A predominant Treg response may blunt CD8+ cytotoxic T cell–mediated killing, but the mechanisms underlying this Treg response are unknown.[Alatrakchi 2009]
Hepatic fibrosis occurring in the setting of chronic hepatitis C is a typical model of wound-healing response to persistent liver injury.[Bataller 2005] Inflammatory cells of the intrahepatic infiltrate secrete cytokines and chemokines capable of activating hepatic stellate cells to secrete collagen.[Heydtmann 2009; Zeremski 2008] Because the latter are a major source of proinflammatory chemokines, a vicious circle ensues, whereby liver inflammation and fibrogenesis amplify each other (Figure 2).[Bataller 2005] Thus, in chronic hepatitis C, the fibrogenic process seems to be linked to viral expression through indirect mechanisms, ie, mediated by virally driven inflammation. A direct role of viral factors in fibrogenesis and disease progression has been debated. Several viral proteins may occasionally induce cell injury, such as oxidative stress and steatosis, probably in a sequence-specific way, and directly activate hepatic stellate cells without the participation of the inflammatory response.[Ming-Ju 2011; Clément 2010] These observations may explain why some patients with chronic hepatitis C may present with significant fibrosis by histology despite persistently normal liver enzymes and minimal/mild inflammation. The mechanisms underlying the direct fibrogenic effects of HCV are undefined."
See: http://www.clinicaloptions.com/inPractice/Hepatology/Hepatology/ch7_Hepatitis_C_Epidemiology_Pathogenesis_Diagnosis_and_Natural_History/Pages/Page%203/subpage%201.aspx
The exact mechanism by which hepatitis C virus (HCV) causes liver cell damage is unknown. High levels of HCV replication have been reported in both immunocompetent and immunosuppressed patients with little or no intrahepatic damage, including inflammation.[McGuinness 1996] Indeed, in patients receiving liver graft as a result of chronic hepatitis C, where HCV infection recurs in virtually all patients, ~ 30% of patients fail to develop recurrent hepatitis 1 year after transplantation despite high levels of HCV replication.[Demetris 2009] It appears as if the host immune system tolerates high levels of intrahepatic HCV replication without killing the infected cells. Putting these observations together, HCV-associated cell damage seems to be largely mediated by the host immune response. Indeed, the hallmark of liver damage associated with HCV infection is a lympho-mononuclear infiltrate mostly represented by CD8+ T cells that are thought to play a major role in viral containment, although other subsets can be detected, such as CD4+, natural killer, and especially regulatory T (Treg) cells.[Spengler 2007] Several investigators have indeed reported how intrahepatic CD4+ and CD8+ cells are specific for different structural and nonstructural HCV antigens.[Koziel 1992; Schirren 2000] Why this immune reaction cannot resolve the infection in most patients is unclear. A predominant Treg response may blunt CD8+ cytotoxic T cell–mediated killing, but the mechanisms underlying this Treg response are unknown.[Alatrakchi 2009]
Hepatic fibrosis occurring in the setting of chronic hepatitis C is a typical model of wound-healing response to persistent liver injury.[Bataller 2005] Inflammatory cells of the intrahepatic infiltrate secrete cytokines and chemokines capable of activating hepatic stellate cells to secrete collagen.[Heydtmann 2009; Zeremski 2008] Because the latter are a major source of proinflammatory chemokines, a vicious circle ensues, whereby liver inflammation and fibrogenesis amplify each other (Figure 2).[Bataller 2005] Thus, in chronic hepatitis C, the fibrogenic process seems to be linked to viral expression through indirect mechanisms, ie, mediated by virally driven inflammation. A direct role of viral factors in fibrogenesis and disease progression has been debated. Several viral proteins may occasionally induce cell injury, such as oxidative stress and steatosis, probably in a sequence-specific way, and directly activate hepatic stellate cells without the participation of the inflammatory response.[Ming-Ju 2011; Clément 2010] These observations may explain why some patients with chronic hepatitis C may present with significant fibrosis by histology despite persistently normal liver enzymes and minimal/mild inflammation. The mechanisms underlying the direct fibrogenic effects of HCV are undefined."
See: http://www.clinicaloptions.com/inPractice/Hepatology/Hepatology/ch7_Hepatitis_C_Epidemiology_Pathogenesis_Diagnosis_and_Natural_History/Pages/Page%203/subpage%201.aspx
1) Your understanding is somewhat correct. The virus doesn't need the liver to replicate. It replicates in the blood where it lives. It just attacks ONLY the liver. White blood cells do not attack the infected liver. Antibodies are created by your immune system and those antibodies attack the virus, not the liver. This period is usually evident by what feels like a really bad flu/cold.
2) Not WBC, but the antibodies fight the virus and it's just up to luck whether the antibodies alone can kill off the virus. Last I checked I think it was somewhere around 15% of people infected get rid of it themselves. If they do not kill the virus, the person has chronic HepC. The interferon is simply medicine which helps your body fight the HepC and kill it. Jsut like any other medicine is meant to help your body fight disease, flus, colds, infections, etc.
3) The only cells that die in treatment are the HepC cells. The WBC and RBC and some other chemistry of your blood are decreased, but the numbers go back to normal after treatment in most people. Hope that helps.
2) Not WBC, but the antibodies fight the virus and it's just up to luck whether the antibodies alone can kill off the virus. Last I checked I think it was somewhere around 15% of people infected get rid of it themselves. If they do not kill the virus, the person has chronic HepC. The interferon is simply medicine which helps your body fight the HepC and kill it. Jsut like any other medicine is meant to help your body fight disease, flus, colds, infections, etc.
3) The only cells that die in treatment are the HepC cells. The WBC and RBC and some other chemistry of your blood are decreased, but the numbers go back to normal after treatment in most people. Hope that helps.
The way I understand it is that the virus replicates in the liver.
Eventually this causes fibrosis in some people. In time this can develop into cirrhosis.
I don't think it has anything to do with WBC.
Some else will probably come along soon who can explain it better than I.
Chok di :)
Eventually this causes fibrosis in some people. In time this can develop into cirrhosis.
I don't think it has anything to do with WBC.
Some else will probably come along soon who can explain it better than I.
Chok di :)
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