Raptly interesting and boggling - system interplay, and the diverse intricate/complicated cellular function and effort to maintain homeostasis!
All you wrote below helps my understanding, especially by example of your own "flares". Provides perspective.
Tig, Thanks. Yes, that was what i meant about TN - TN just being "versus" to someone IN treatment (who we wish/expect to see a VL drop in!). Your comments about fluctuation ALT levels, low or persisting abnormal ALT's support all that Mallani outlines and what I have become aware of as well.
It was just the introduction of the thought about HCV "in" the lymphocyte that I had never given much thought to before, so intrigued me and led me to trying to see a useful co-relation between replication/VL spikes and lymphocytes levels. Generally we can count on the ALT telling the liver inflammation/damage/dysfunction story quite well enough, and as most people know the HCV is not "confined to the liver organ" alone, but of course is a systemic disease, thus why we can see so many system effects/affects in play.
All immensely interesting to me. Thanks you two. . C
mallani said
Apr 2, 2016
The liver is a very dynamic organ, with constant apoptosis/remodeling.
Hepatocytes die off, releasing enzymes. New hepatocytes generate. In cirrhotics, the nodules often have poor blood supply, so the cycle of apoptosis/necrosis and regeneration is more profound.
Even though some cirrhotics have relatively normal enzymes, most are 2 or 3 times the ULN. This happens in all cirrhotics, whatever the cause.
Add the insult of HCV infection, and the hepatocytes show more damage and death.
Looking at my enzymes and VL over almost 30 years, there are several flares, where the VL and ALT are considerably elevated. The disease process appears to rumble along, with no obvious reason for the 'flares'.
As I never had any symptoms of HepC, these flares were not apparent. In others, this may be noticeable.
My ALT dropped during my 48 weeks of treatment, but was never normal. Even at SVR 12, my ALT was still 59.
Total lymphocyte count is always elevated in a chronic viral illness. The level is not important unless it's through the roof, when lymphoma should be considered.
Tig said
Apr 1, 2016
Canuck,
It doesn't matter if you're TN or TE, it will be quite normal for someone with CHC to witness extreme fluctuations in their viral load (flares). Of course once Tx has begun, that should drop into oblivion, at some stage of the process anyway! The LFT's (enzymes) may respond with an elevation, but they tend to be more of an indication of liver function in CHC. I have seen people with high viral loads have a normal ALT and AST. The ALT tends to be more liver specific and spikes in it can mean increasing activity/damage. It will also elevate when certain medications are used regularly or in high doses, NSAIDs in particular.
The thing to remember is during treatment, it isn't uncommon to see your enzymes fluctuate. Some people, especially cirrhotics may continue to see elevated ALT results, even with an undetected VL.
Canuck said
Apr 1, 2016
Hey,
Thanks guys for the attempted tutorial. Appreciate it. All knowledge is good (what I can absorb), so, if things were easier to comprehend, I would be ahead!
Good to focus on what I think I already "kind of" understand, but glad you stated plainly the "non-direct relationship" between fluctuating VL's and lymphocyte levels - that helps nip that errant pondering of mine in the bud. Yes I agree, T and B will only hurt my head.
I agree to default back to the ALT being the easy-indicator tool for rule of thumb judging of "activity" - but in the case of a sudden spikes or decreases in VL in chronic HCV (in the TN), wouldn't one expect to see at least some subtle corresponding upward/downward changes in the ALT then? C.
mallani said
Mar 29, 2016
Hi Canuck,
Don't get too worried about lymphocytes.
There is no doubt they play a major role in HCV infections.
The virus can replicate in peripheral blood monocytes (part of the WBC family).
Lymphocytes produce the cryoglobulins that cause many of the extra-hepatic manifestations, and the increased risk of lymphoma.
There is no correlation between the absolute lymphocyte count and viral activity. The VL is independent to the WCC.
Don't worry about T-cells and B-cells. That will only give you a headache.
Really, the ALT level is the best indicator of viral activity. Forget the GGT and AST. Cheers.
Tig said
Mar 25, 2016
Hey C,
You're very close to rupturing one of my cerebral blood vessels! I can't address the subject on lymphocytic response and replication, but do have some information that helps explain the action they undergo during immune responses to viruses. I do know that they have determined a primary replication point is in the hepatocytes. It's all very complex and I only understand every fourth or fifth word... I'll include some links to some additional data.
Old but descriptive: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083516/pdf/jvh0015-0849.pdf
Canuck said
Mar 25, 2016
Re: HCV being anywhere in a person's body?
I was interested in what Mallani said, about HCV having an affinity "in lymphocytes", so, I started googling up (fairly old) studies done about the relationships between lymphocytes and HCV, trying to find out more about HCV "in" lymphocytes, and about replication in general - below is just one study (and excerpt) that happened to be "more recent", there were lots that were old. Most of the studies I skimmed were and will ALWAYS be WELL beyond me! With no grasp on "cellular science", I was hoping it would be easier to find a simple way to fathom this premise of "HCV in lymphocytes" thing - a simple-minded person wanting to stumble across something comprehensible that would at least help me gel some kind of "useful" understanding between immune response/lymphocytes/the HCV relationship. i.e. -"Is there an easy, reliable way for a person to guess that (generally) when they see their lymphoctye counts increasing, they might expect to see their viral load decreasing in response, and conversely, when they see their lymphoctye counts droppings, they might expect to see an increase VL in response"?? I highly expect there will be no nice, neat, simple answer, when I skim events like "lymphocyte exhaustion" and such! What studies I did skim on lymphocyte/B/T cells and their relationship in HCV seems just as greek to me as trying to understand the basic concepts in HIV!! Never gonna happen - I can't find the easy lymphocyte tutorial 101 that is simple enough but broad enough to answer my own naive questions about fluctuating HCV loads.
Aside from how we see ALT/AST as a being "rough indicators", can your other blood parameters be used, in such a simple fashion as I have wondered about - lymphocyte levels and VL drops and increases?
... "It is well recognized that HCV-specific CD4+ T cell response in individuals chronically infected with HCV is poor or absent [26]. In HCV-infected patients who transiently control viremia and have fluctuating plasma viral load, including periods of apparent HCV RNA negativity, this transient viral control is accompanied by increased virus-specific CD4+ T cell response [26]. In patients with CHC, T cells have been found to be impaired in the production of IFN- and IL-2 [12]. As well, studies investigating CD4+ T cell function during a symptomatic persistent HCV infection have shown a significant loss of IL-2 secreting cells compared to individuals who spontaneously resolved viremia, as well as a weak IFN- production by HCV-specific CD4+ T cells upon stimulation [27]." ...
Hey thnaks,
Yes, AMAZINGLY "dynamic"!
Raptly interesting and boggling - system interplay, and the diverse intricate/complicated cellular function and effort to maintain homeostasis!
All you wrote below helps my understanding, especially by example of your own "flares". Provides perspective.
Tig, Thanks. Yes, that was what i meant about TN - TN just being "versus" to someone IN treatment (who we wish/expect to see a VL drop in!). Your comments about fluctuation ALT levels, low or persisting abnormal ALT's support all that Mallani outlines and what I have become aware of as well.
It was just the introduction of the thought about HCV "in" the lymphocyte that I had never given much thought to before, so intrigued me and led me to trying to see a useful co-relation between replication/VL spikes and lymphocytes levels. Generally we can count on the ALT telling the liver inflammation/damage/dysfunction story quite well enough, and as most people know the HCV is not "confined to the liver organ" alone, but of course is a systemic disease, thus why we can see so many system effects/affects in play.
All immensely interesting to me. Thanks you two.
. C
The liver is a very dynamic organ, with constant apoptosis/remodeling.
Hepatocytes die off, releasing enzymes. New hepatocytes generate. In cirrhotics, the nodules often have poor blood supply, so the cycle of apoptosis/necrosis and regeneration is more profound.
Even though some cirrhotics have relatively normal enzymes, most are 2 or 3 times the ULN. This happens in all cirrhotics, whatever the cause.
Add the insult of HCV infection, and the hepatocytes show more damage and death.
Looking at my enzymes and VL over almost 30 years, there are several flares, where the VL and ALT are considerably elevated. The disease process appears to rumble along, with no obvious reason for the 'flares'.
As I never had any symptoms of HepC, these flares were not apparent. In others, this may be noticeable.
My ALT dropped during my 48 weeks of treatment, but was never normal. Even at SVR 12, my ALT was still 59.
Total lymphocyte count is always elevated in a chronic viral illness. The level is not important unless it's through the roof, when lymphoma should be considered.
Canuck,
It doesn't matter if you're TN or TE, it will be quite normal for someone with CHC to witness extreme fluctuations in their viral load (flares). Of course once Tx has begun, that should drop into oblivion, at some stage of the process anyway! The LFT's (enzymes) may respond with an elevation, but they tend to be more of an indication of liver function in CHC. I have seen people with high viral loads have a normal ALT and AST. The ALT tends to be more liver specific and spikes in it can mean increasing activity/damage. It will also elevate when certain medications are used regularly or in high doses, NSAIDs in particular.
The thing to remember is during treatment, it isn't uncommon to see your enzymes fluctuate. Some people, especially cirrhotics may continue to see elevated ALT results, even with an undetected VL.
Hey,
Thanks guys for the attempted tutorial. Appreciate it. All knowledge is good (what I can absorb), so, if things were easier to comprehend, I would be ahead!
Good to focus on what I think I already "kind of" understand, but glad you stated plainly the "non-direct relationship" between fluctuating VL's and lymphocyte levels - that helps nip that errant pondering of mine in the bud. Yes I agree, T and B will only hurt my head.
I agree to default back to the ALT being the easy-indicator tool for rule of thumb judging of "activity" - but in the case of a sudden spikes or decreases in VL in chronic HCV (in the TN), wouldn't one expect to see at least some subtle corresponding upward/downward changes in the ALT then?
C.
Hi Canuck,
Don't get too worried about lymphocytes.
There is no doubt they play a major role in HCV infections.
The virus can replicate in peripheral blood monocytes (part of the WBC family).
Lymphocytes produce the cryoglobulins that cause many of the extra-hepatic manifestations, and the increased risk of lymphoma.
There is no correlation between the absolute lymphocyte count and viral activity. The VL is independent to the WCC.
Don't worry about T-cells and B-cells. That will only give you a headache.
Really, the ALT level is the best indicator of viral activity. Forget the GGT and AST. Cheers.
Hey C,
You're very close to rupturing one of my cerebral blood vessels! I can't address the subject on lymphocytic response and replication, but do have some information that helps explain the action they undergo during immune responses to viruses. I do know that they have determined a primary replication point is in the hepatocytes. It's all very complex and I only understand every fourth or fifth word... I'll include some links to some additional data.
http://www.hepatitiscentral.com/hcv/labs/lymphocytes/
Old but descriptive: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083516/pdf/jvh0015-0849.pdf
Re: HCV being anywhere in a person's body?
I was interested in what Mallani said, about HCV having an affinity "in lymphocytes", so, I started googling up (fairly old) studies done about the relationships between lymphocytes and HCV, trying to find out more about HCV "in" lymphocytes, and about replication in general - below is just one study (and excerpt) that happened to be "more recent", there were lots that were old. Most of the studies I skimmed were and will ALWAYS be WELL beyond me! With no grasp on "cellular science", I was hoping it would be easier to find a simple way to fathom this premise of "HCV in lymphocytes" thing - a simple-minded person wanting to stumble across something comprehensible that would at least help me gel some kind of "useful" understanding between immune response/lymphocytes/the HCV relationship. i.e. - "Is there an easy, reliable way for a person to guess that (generally) when they see their lymphoctye counts increasing, they might expect to see their viral load decreasing in response, and conversely, when they see their lymphoctye counts droppings, they might expect to see an increase VL in response"?? I highly expect there will be no nice, neat, simple answer, when I skim events like "lymphocyte exhaustion" and such! What studies I did skim on lymphocyte/B/T cells and their relationship in HCV seems just as greek to me as trying to understand the basic concepts in HIV!! Never gonna happen - I can't find the easy lymphocyte tutorial 101 that is simple enough but broad enough to answer my own naive questions about fluctuating HCV loads.
Aside from how we see ALT/AST as a being "rough indicators", can your other blood parameters be used, in such a simple fashion as I have wondered about - lymphocyte levels and VL drops and increases?
http://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0322-4
... "It is well recognized that HCV-specific CD4+ T cell response in individuals chronically infected with HCV is poor or absent [26]. In HCV-infected patients who transiently control viremia and have fluctuating plasma viral load, including periods of apparent HCV RNA negativity, this transient viral control is accompanied by increased virus-specific CD4+ T cell response [26]. In patients with CHC, T cells have been found to be impaired in the production of IFN- and IL-2 [12]. As well, studies investigating CD4+ T cell function during a symptomatic persistent HCV infection have shown a significant loss of IL-2 secreting cells compared to individuals who spontaneously resolved viremia, as well as a weak IFN- production by HCV-specific CD4+ T cells upon stimulation [27]." ...
blah, blah, blah - Greek!
Hurting my small head. C .