Aa
Great news!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! and open post
Just Got my HGB and FINALLY it stopped dropping!!!!!!!!!!!!!!
It's still at 7.3 and I will not need transfusion!!!!!!!!!!!!!!!!
With 4 1/2 left I should be ok :)
BEAGLE BAILEY!!!!!!!!!!!!!!!!!!!!!!!
It's still at 7.3 and I will not need transfusion!!!!!!!!!!!!!!!!
With 4 1/2 left I should be ok :)
BEAGLE BAILEY!!!!!!!!!!!!!!!!!!!!!!!
MR. BB,
YEAH!!!!!!!!!!!!!!!!!!! I told you ,I just knew you were going to get a grip on those blood counts. CONGRADULATIONS BB. You are almost there. Glad to hear you will be going home to visit; tell all hello and hope all is well.
I know ,I have not been on in awhile, lots going on and just trying to be as normal as I can on this tx. If thats even possible at times. You mentioned Orange County on our last conversation. Good Area, we have friends that bought a home in Costa Mesa. That is just inland from the beach area. Your son lives in a nice area. If you truely wanted to make a move at your time in retirement; you could probably do it. With your wife in management, she will have no problems getting a position in that field. Will try to get a pay scale for you on that; sure it will vary, depending on the type of business. The weather here is finally giving more sunny days. It is really starting to feel like the normal California weather I am used to.
In general, if you do not try to buy right on the beach, you can afford to live here. Just come inland a little and things in cost change.
NYGIRL: .44 HUH!!! You go girl. I have a .357, first gun I learned how to shoot without aiming. Just turn and shoot your target. That was many years ago. Still have the .357 though. I am so glad that you decided not to take out your family; that damned old RIBA.
LOVE TO ALL HERE ON THE FORUM!!!!!!!!!
Cajun
YEAH!!!!!!!!!!!!!!!!!!! I told you ,I just knew you were going to get a grip on those blood counts. CONGRADULATIONS BB. You are almost there. Glad to hear you will be going home to visit; tell all hello and hope all is well.
I know ,I have not been on in awhile, lots going on and just trying to be as normal as I can on this tx. If thats even possible at times. You mentioned Orange County on our last conversation. Good Area, we have friends that bought a home in Costa Mesa. That is just inland from the beach area. Your son lives in a nice area. If you truely wanted to make a move at your time in retirement; you could probably do it. With your wife in management, she will have no problems getting a position in that field. Will try to get a pay scale for you on that; sure it will vary, depending on the type of business. The weather here is finally giving more sunny days. It is really starting to feel like the normal California weather I am used to.
In general, if you do not try to buy right on the beach, you can afford to live here. Just come inland a little and things in cost change.
NYGIRL: .44 HUH!!! You go girl. I have a .357, first gun I learned how to shoot without aiming. Just turn and shoot your target. That was many years ago. Still have the .357 though. I am so glad that you decided not to take out your family; that damned old RIBA.
LOVE TO ALL HERE ON THE FORUM!!!!!!!!!
Cajun
hahahahaahaha I'm telling you between the family, the office and the Riba Road Rage - it gets close sometimes! I might be better off getting rid of the gun and getting like a Gumby doll...then I can drive down the road and flash the old gumby at them and watch the reactions....ought to be more effective than any .44 right?
(OK Can and Goof I hear ya...I hear ya)... LOL
(OK Can and Goof I hear ya...I hear ya)... LOL
<u>cuteus</u>
(from your post/questions below):
"<i>When I glanced at the Pham abstract, with its limited information, it does seem to address mostly post tx subjects, but even though it stated "The findings show that HCV RNA was carried in the convalescent-phase sera and/or PBMC in all 16 individuals investigated." it added "Importantly, traces of the HCV RNA negative strand, suggesting progressing virus replication, were detected in the majority of mitogen-stimulated PBMC, including four samples collected 5 years after recovery. Sequencing of the HCV 5' untranslated region fragment revealed genotype 1b in four of nine individuals examined and genotypes 1a and 2a in three and two patients, respectively."
Does it mean that negative strands were not found in the other 7?</i>"
In this particular study by <a href="http://jvi.asm.org/cgi/content/full/78/11/5867?view=long&pmid=15140984">Pham et all (2004)</a>, 5 of the patients were spontaneous clearer's (SC) and 11 were SVR's (data pulled from <a href="http://jvi.asm.org/cgi/content/full/78/11/5867/T1">this table</a>). Also, in looking at the table, it appears that of the 5 SC's - 2 were negative strand (NS) positive, 1 was NS negative, 1 was not tested (NT) and 1 listed as not available/not applicable (NA). Of the 11 SVR's - 7 were NS positive, 2 were NS negative, 2 NT and 1 NA. So, overall 9 out of 16 (75%) were NS positive.
(from the "Discussion" portion of the paper (about 2/3 the way down), the authors conclude the following):
"<i>...analysis showed that trace virus replication persisted in the lymphatic system in the majority (75%) of persons from whom sufficient numbers of PBMC were available for investigation. This finding is not surprising, considering that several laboratories have shown the presence of the HCV RNA replicative strand in peripheral and organ lymphoid cells of patients with chronic hepatitis C (7, 17, 23, 37), as we also found in this study (Fig. 6). The present data clearly indicate that carriage of HCV in peripheral lymphoid cells is not terminated at the time of clinical resolution of chronic hepatitis C, but rather it subsides to a level that is not readily detectable by the currently used laboratory assays, and the virus genome persists at these low levels for a long time after apparently complete recovery.</i>"
(from your next set of questions):
"<i>aren't some of the subjects in the occult issue, only positive in the liver? meaning that no antibodies were ever created by their system? Does it not mean that for some reason, the virus settled in the liver and never went into the serum, thus avoiding detection by the immune system? or that the system never developed antibodies for some other reason? I know some had detectable antibodies with no VL, but others had a negative in both tests? In that case, their immune system never develop the cells to attack the virus, or the antibodies completely dissappeared from their blood, while the virus remained in hepatic tissue/pbmc?</i>".
The <a href="http://www.natap.org/2005/HCV/090505_20.htm">Castillo et al 2004</a> paper looked at 100 patients who had no Hep C antibodies, no serum RNA, but had elevated LFT's. 57 were determined to have occult, based upon liver PCR. 48 of the 57 (84.2%) with occult were NS positive in the liver. 40 of the 57 were PBMC RNA positive. Of the 40, 35 (87.5%) were PBMC NS positive. The authors mention that "<i>...no correlation between its (NS) presence in the liver and infection of the PBMCs was found.</i>"
The authors don't speculate as to how the immune systems of the patients reacted (or not) to the presence of the virus. You mention the two most probabilistic answers: 1.) the antibodies completely cleared from serum over time (not unheard of in some patients over 10-20 years or more) or, 2.) that the immune system never recognized the invasion in the first place and an occult level of infection slipped in "under the radar" (though I'm not too sure how or why the virus would stay at "occult level" when being given such a huge "free pass" from the immune system).
(from your next set of questions):
"<i>Could it not be possible that one manner of eradication/suppression is more effective than the other, in the post tx period? If SVRs are showing negative strands, post tx(and it does not seem like all of them are), is their immune response actively suppressing or maybe still eradicating?</i>"
It's possible that the immune system response of SVR's is somewhat different than those of SC's, thereby possibly creating a differing response to occult between these two sub-groups. I just haven't seen any of the studies mentioning any distinguishing differences.
You're asking all the tough/right questions. One avenue might be to pose them to Pham and/or any other researchers into occult or basic virology and see what they tell you. I'd be happy to read their thoughts and opinions.
<u>willing</u> - didn't you post a paper a bit ago discussing possible differing t-cell responses between post-interferon patients vs. SC's, or am I confusing that with something else?
Also, any thoughts to add on any of the above?
TnHepGuy
(from your post/questions below):
"<i>When I glanced at the Pham abstract, with its limited information, it does seem to address mostly post tx subjects, but even though it stated "The findings show that HCV RNA was carried in the convalescent-phase sera and/or PBMC in all 16 individuals investigated." it added "Importantly, traces of the HCV RNA negative strand, suggesting progressing virus replication, were detected in the majority of mitogen-stimulated PBMC, including four samples collected 5 years after recovery. Sequencing of the HCV 5' untranslated region fragment revealed genotype 1b in four of nine individuals examined and genotypes 1a and 2a in three and two patients, respectively."
Does it mean that negative strands were not found in the other 7?</i>"
In this particular study by <a href="http://jvi.asm.org/cgi/content/full/78/11/5867?view=long&pmid=15140984">Pham et all (2004)</a>, 5 of the patients were spontaneous clearer's (SC) and 11 were SVR's (data pulled from <a href="http://jvi.asm.org/cgi/content/full/78/11/5867/T1">this table</a>). Also, in looking at the table, it appears that of the 5 SC's - 2 were negative strand (NS) positive, 1 was NS negative, 1 was not tested (NT) and 1 listed as not available/not applicable (NA). Of the 11 SVR's - 7 were NS positive, 2 were NS negative, 2 NT and 1 NA. So, overall 9 out of 16 (75%) were NS positive.
(from the "Discussion" portion of the paper (about 2/3 the way down), the authors conclude the following):
"<i>...analysis showed that trace virus replication persisted in the lymphatic system in the majority (75%) of persons from whom sufficient numbers of PBMC were available for investigation. This finding is not surprising, considering that several laboratories have shown the presence of the HCV RNA replicative strand in peripheral and organ lymphoid cells of patients with chronic hepatitis C (7, 17, 23, 37), as we also found in this study (Fig. 6). The present data clearly indicate that carriage of HCV in peripheral lymphoid cells is not terminated at the time of clinical resolution of chronic hepatitis C, but rather it subsides to a level that is not readily detectable by the currently used laboratory assays, and the virus genome persists at these low levels for a long time after apparently complete recovery.</i>"
(from your next set of questions):
"<i>aren't some of the subjects in the occult issue, only positive in the liver? meaning that no antibodies were ever created by their system? Does it not mean that for some reason, the virus settled in the liver and never went into the serum, thus avoiding detection by the immune system? or that the system never developed antibodies for some other reason? I know some had detectable antibodies with no VL, but others had a negative in both tests? In that case, their immune system never develop the cells to attack the virus, or the antibodies completely dissappeared from their blood, while the virus remained in hepatic tissue/pbmc?</i>".
The <a href="http://www.natap.org/2005/HCV/090505_20.htm">Castillo et al 2004</a> paper looked at 100 patients who had no Hep C antibodies, no serum RNA, but had elevated LFT's. 57 were determined to have occult, based upon liver PCR. 48 of the 57 (84.2%) with occult were NS positive in the liver. 40 of the 57 were PBMC RNA positive. Of the 40, 35 (87.5%) were PBMC NS positive. The authors mention that "<i>...no correlation between its (NS) presence in the liver and infection of the PBMCs was found.</i>"
The authors don't speculate as to how the immune systems of the patients reacted (or not) to the presence of the virus. You mention the two most probabilistic answers: 1.) the antibodies completely cleared from serum over time (not unheard of in some patients over 10-20 years or more) or, 2.) that the immune system never recognized the invasion in the first place and an occult level of infection slipped in "under the radar" (though I'm not too sure how or why the virus would stay at "occult level" when being given such a huge "free pass" from the immune system).
(from your next set of questions):
"<i>Could it not be possible that one manner of eradication/suppression is more effective than the other, in the post tx period? If SVRs are showing negative strands, post tx(and it does not seem like all of them are), is their immune response actively suppressing or maybe still eradicating?</i>"
It's possible that the immune system response of SVR's is somewhat different than those of SC's, thereby possibly creating a differing response to occult between these two sub-groups. I just haven't seen any of the studies mentioning any distinguishing differences.
You're asking all the tough/right questions. One avenue might be to pose them to Pham and/or any other researchers into occult or basic virology and see what they tell you. I'd be happy to read their thoughts and opinions.
<u>willing</u> - didn't you post a paper a bit ago discussing possible differing t-cell responses between post-interferon patients vs. SC's, or am I confusing that with something else?
Also, any thoughts to add on any of the above?
TnHepGuy
I truly appreciate that input, I know it can be very time consuming to do that, geesh I never finished reading all the FCO ASLD presentations from the link willing posted before they dissappeared from that site, but I got enough in, and surprisingly can remember enough!
That is truly fascinating findings, so we still don't know if all SVRs are showing persistent HCV, I will wait for the next corrobariting or refuting studies and keep my eyes open.
As for contacting the researchers, I never considered the possibility that they would have the time to answer our questions, but I will give it a thought. I might not sound as technical as you or willing, though.
thanks again!
That is truly fascinating findings, so we still don't know if all SVRs are showing persistent HCV, I will wait for the next corrobariting or refuting studies and keep my eyes open.
As for contacting the researchers, I never considered the possibility that they would have the time to answer our questions, but I will give it a thought. I might not sound as technical as you or willing, though.
thanks again!
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