Aa
Occult Virus----(Clearing Naturally)
I wonder if the "occult virus" was ever detected in the liver of someone who cleared on their own?...i dont expect an answer to this question anytime soon,because of the newness of this" occult delimma"
I would edit the above confusion but can't find the mechanism, but my 16 wk post tx PCR was undie to <5 iu/ml
the quote was from an above post that stated 'occult' virus is not necessarily related to enzyme level.
the quote was from an above post that stated 'occult' virus is not necessarily related to enzyme level.
I've been trying to follow this thread for the last couple weeks. I finished 24 wk tx last August for geno 3a. Four week PCR was 18iu/ml measurable to <5. All other PCR's were only measured to <50. .. all were undie. I had one done at 16 wks post tx and it was again undie to In addition to the documentation of HCV RNA
in serum or plasma, PBMC and hepatic tissue in
patients with resolved hepatitis C in whom alanine
aminotransferase (ALT) levels were deemed repeatedly
normal. . .. <unquote
I'm posting this in case anyone may care to offer an opinion. I don't have access to a liver specialist and I don't expect to at any foreseeable time in the future.
I appreciate the level of interest and knowledge at this board. Haven't found it anywhere else.
kind regards,
Max
PS I imagine most everyone has seen this study, but I'll post it just in case. Our livers do get healthier post SVR, and there's proof:
http://www3.interscience.wiley.com/cgi-bin/fulltext/121477214/HTMLSTART?CRETRY=1&SRETRY=0
in serum or plasma, PBMC and hepatic tissue in
patients with resolved hepatitis C in whom alanine
aminotransferase (ALT) levels were deemed repeatedly
normal. . .. <unquote
I'm posting this in case anyone may care to offer an opinion. I don't have access to a liver specialist and I don't expect to at any foreseeable time in the future.
I appreciate the level of interest and knowledge at this board. Haven't found it anywhere else.
kind regards,
Max
PS I imagine most everyone has seen this study, but I'll post it just in case. Our livers do get healthier post SVR, and there's proof:
http://www3.interscience.wiley.com/cgi-bin/fulltext/121477214/HTMLSTART?CRETRY=1&SRETRY=0
Recognizable pos. and neg. strand HCV RNA is found in both those who clear the virus on their own and those who clear with IFN at about the same rate last time I checked - around 85-90% of the time. This isn't new stuff. I spent half a Sat. morning two years ago arguing this with Kalio who was sure "clear means clear" and that I pulled the # 85-90% out of thin air. There are multiple studies that give numbers bracketing this range, but I'm not going to look them up again - it's all in the archives.
I wouldn't worry about "incapacitated HCV mutants" (HR's phrase). There's enough real stuff in this world to think about. Most of us probably carry 'occult' varicella-zoster virus
http://www.nfid.org/pdf/factsheets/varicellaadult.pdf
And then there's Methicillin Resistant Staph. A
I wouldn't worry about "incapacitated HCV mutants" (HR's phrase). There's enough real stuff in this world to think about. Most of us probably carry 'occult' varicella-zoster virus
http://www.nfid.org/pdf/factsheets/varicellaadult.pdf
And then there's Methicillin Resistant Staph. A
I'd also like to second some of Mike's comments earlier in the thread "that we should be careful not to alarm members when, as far as I know, there is, as yet, no fact based evidence for alarm". In fact, no clinical significance has been demonstrated by the purported phenomenom.
------------------------------
HR's take on the signficance of let's call it "SVR Occult" is as follows per the thread previously noted:
To: Trihep
" - What are the possibilities of occult SVR's being able to transmit the virus?
(HR) Most likely negligible, since not even full blown VLs with fit virus in the 5o Million/ml range are very transmissible in the sexual context.
"- And if the majority of occult infection is made of 'unfit' viral remnants, how might the immune system of an uninfected individual who became exposed (via transfusion, IV drug use, needle stick, etc) respond? Would you expect their immune system to 'trap' and treat it in the same way - creating a low level 'balance' with a chronic infection remaining? Or might a healthy immune system be able to fully 'knock back' the occult infection to the point where negative strand replication no longer takes place? "
(HR) Such an infection will probably not take hold to any degree that matters. It has become a "non-pathogenic' virus, a lame and tame dog out of a Wolfe....
Questions like that will also have a very low chance of being investigated, since they are very difficult to examine and have a clinical impact too low to matter in a world filled with more obvious diseases and dilemmas.
--------
I'm reluctant to paraphrase HR, but my take is that he clearly does not see any concern for alarm in SVRs nor does he see further investigationa pressing issue in a world filled with more obvious diseases and dilemmas".
My own take -- gleaned from the doctors I"ve spoken to -- is a little less generous on the subject as they have both questioned the research methodology itself as well as the conclusions. Nothing to debate here, I'm just relaying on information. That's their opinion. HR's opinion speaks for itself. Lots of opinions here :)
-- Jim
------------------------------
HR's take on the signficance of let's call it "SVR Occult" is as follows per the thread previously noted:
To: Trihep
" - What are the possibilities of occult SVR's being able to transmit the virus?
(HR) Most likely negligible, since not even full blown VLs with fit virus in the 5o Million/ml range are very transmissible in the sexual context.
"- And if the majority of occult infection is made of 'unfit' viral remnants, how might the immune system of an uninfected individual who became exposed (via transfusion, IV drug use, needle stick, etc) respond? Would you expect their immune system to 'trap' and treat it in the same way - creating a low level 'balance' with a chronic infection remaining? Or might a healthy immune system be able to fully 'knock back' the occult infection to the point where negative strand replication no longer takes place? "
(HR) Such an infection will probably not take hold to any degree that matters. It has become a "non-pathogenic' virus, a lame and tame dog out of a Wolfe....
Questions like that will also have a very low chance of being investigated, since they are very difficult to examine and have a clinical impact too low to matter in a world filled with more obvious diseases and dilemmas.
--------
I'm reluctant to paraphrase HR, but my take is that he clearly does not see any concern for alarm in SVRs nor does he see further investigationa pressing issue in a world filled with more obvious diseases and dilemmas".
My own take -- gleaned from the doctors I"ve spoken to -- is a little less generous on the subject as they have both questioned the research methodology itself as well as the conclusions. Nothing to debate here, I'm just relaying on information. That's their opinion. HR's opinion speaks for itself. Lots of opinions here :)
-- Jim
The terms "persistent" and "occult" are have been used interchangeable by various researchers and here (see Mikes post, above) it's fused as "persistent occult", perhaps a compromise, or perhaps a newly discovered mutant :) I believe the last paper posted here on the subject was also titled and referred to as "occult" even though the infection was resolved as in SVR. Later, it was referred to in the thread as "occult SVRs" in a question to which HR responded to here: http://www.medhelp.org/posts/show/763749?post_id=post_4022709
The distiniction as I see it is not in the name "occult" or "persistent" but in the precise definition you want to give the phenomenon.
The distiniction as I see it is not in the name "occult" or "persistent" but in the precise definition you want to give the phenomenon.
IDENTIFICATION OF OCCULT HCV
INFECTION
In the past four years, the identifi cation of a new entity of
HCV infection termed as occult HCV infection was made
possible by the introduction of research assays which are
capable of detecting HCV RNA at lower quantities (≤
2 IU or ≤ 10 virus genome copies per mL) than those
used in clinical laboratories. One such research assay
sequentially involves: (1) a reverse transcription (RT) of
high quality intact total RNA extracted from serum or
plasma, peripheral blood mononuclear cells (PBMC) or,
when feasible, hepatic tissues; (2) a two-round (i.e., direct
and nested) amplification of the resulting cDNA by
polymerase chain reaction (PCR) using primers spanning
different regions of the HCV genome; and (3) validation
of the amplified products by nucleic acid hybridization
(NAH) to recombinant HCV DNA probe[8]. By employing
this assay or those with comparable sensitivities, low levels
of HCV RNA can be detected in individuals for many
years after clinical and biochemical recovery from hepatitis
C[9-12]. In our studies, HCV RNA loads, as determined
by the aformentioned method, in individuals who were
followed for up to 7 years after SVR, were usually below
100 virus copies per mL of plasma or serum and, in most
cases, ranged 100-1000 virus copies per 107 circulating
lymphoid cells[9,13]. Comparable levels of HCV genomes
were also observed by others[10]. Furthermore, longitudinal
analyses of serum or plasma and PBMC samples obtained
from the same patients at different time points of SVR
duration or after spontaneous recovery from hepatitis C
revealed that HCV RNA typically would not fl uctuate by
more than ten-fold between collections and that screening
sequential samples enhanced identifi cation of occult HCV
persistence[8,13,14]. In this regard, when serum samples
collected 12 mo after the first one were analyzed, the
overall HCV RNA positivity was increased by as much as
15% of the cases examined[13].
The discovery of occult HCV infection has, in essence,
directly challenged the accepted paradigm that apparent
complete resolution of hepatitis C, either spontaneously or
therapeutically-induced, would be indicative of eradication
of HCV[8]. It should be pointed out that although HCV
persistence after resolution of CHC was fi rst made evident
from studies using the RT-PCR/NAH or equivalent
research assays, data from more recent studies suggested
that this form of clinically unapparent, but molecularly
evident HCV infection could also be identified when
clinical assays of enhanced sensitivity are employed. On
this note, it was reported that using the Roche Cobas-
Amplicor assay (sensitivity: 50 virus copies/mL), HCV
RNA was detected in freshly isolated blood mononuclear
cells of approximately 20% of individuals with clinical
SVR[12]. Furthermore, in another study conducted by
another group, over 11% of CHC patients who initially
failed IFNα monotherapy, but achieved clinical SVR after
successful completion of P-IFNα/RBV were also found
to carry residual HCV RNA when their sera were tested by
the Cobas-Amplicor assay[15].
In addition to the documentation of HCV RNA
in serum or plasma, PBMC and hepatic tissue in
patients with resolved hepatitis C in whom alanine
aminotransferase (ALT) levels were deemed repeatedly
normal, HCV genomes were also identified in the same
three aforementioned compartments in patients with
persistently elevated liver enzymes, who were consistently
negative for serological markers typical of a bona fi de HCV
infection[11,16-18].
INFECTION
In the past four years, the identifi cation of a new entity of
HCV infection termed as occult HCV infection was made
possible by the introduction of research assays which are
capable of detecting HCV RNA at lower quantities (≤
2 IU or ≤ 10 virus genome copies per mL) than those
used in clinical laboratories. One such research assay
sequentially involves: (1) a reverse transcription (RT) of
high quality intact total RNA extracted from serum or
plasma, peripheral blood mononuclear cells (PBMC) or,
when feasible, hepatic tissues; (2) a two-round (i.e., direct
and nested) amplification of the resulting cDNA by
polymerase chain reaction (PCR) using primers spanning
different regions of the HCV genome; and (3) validation
of the amplified products by nucleic acid hybridization
(NAH) to recombinant HCV DNA probe[8]. By employing
this assay or those with comparable sensitivities, low levels
of HCV RNA can be detected in individuals for many
years after clinical and biochemical recovery from hepatitis
C[9-12]. In our studies, HCV RNA loads, as determined
by the aformentioned method, in individuals who were
followed for up to 7 years after SVR, were usually below
100 virus copies per mL of plasma or serum and, in most
cases, ranged 100-1000 virus copies per 107 circulating
lymphoid cells[9,13]. Comparable levels of HCV genomes
were also observed by others[10]. Furthermore, longitudinal
analyses of serum or plasma and PBMC samples obtained
from the same patients at different time points of SVR
duration or after spontaneous recovery from hepatitis C
revealed that HCV RNA typically would not fl uctuate by
more than ten-fold between collections and that screening
sequential samples enhanced identifi cation of occult HCV
persistence[8,13,14]. In this regard, when serum samples
collected 12 mo after the first one were analyzed, the
overall HCV RNA positivity was increased by as much as
15% of the cases examined[13].
The discovery of occult HCV infection has, in essence,
directly challenged the accepted paradigm that apparent
complete resolution of hepatitis C, either spontaneously or
therapeutically-induced, would be indicative of eradication
of HCV[8]. It should be pointed out that although HCV
persistence after resolution of CHC was fi rst made evident
from studies using the RT-PCR/NAH or equivalent
research assays, data from more recent studies suggested
that this form of clinically unapparent, but molecularly
evident HCV infection could also be identified when
clinical assays of enhanced sensitivity are employed. On
this note, it was reported that using the Roche Cobas-
Amplicor assay (sensitivity: 50 virus copies/mL), HCV
RNA was detected in freshly isolated blood mononuclear
cells of approximately 20% of individuals with clinical
SVR[12]. Furthermore, in another study conducted by
another group, over 11% of CHC patients who initially
failed IFNα monotherapy, but achieved clinical SVR after
successful completion of P-IFNα/RBV were also found
to carry residual HCV RNA when their sera were tested by
the Cobas-Amplicor assay[15].
In addition to the documentation of HCV RNA
in serum or plasma, PBMC and hepatic tissue in
patients with resolved hepatitis C in whom alanine
aminotransferase (ALT) levels were deemed repeatedly
normal, HCV genomes were also identified in the same
three aforementioned compartments in patients with
persistently elevated liver enzymes, who were consistently
negative for serological markers typical of a bona fi de HCV
infection[11,16-18].
Once again I will insert a clarification regarding Occult HCV and Persistent HCV, which I believe draws a difference between the two forms of virus, and would seem to indicate that the two terms should not be used interchangably.
Occult HCV has often turned up in people who have no measurable blood infection, or those who are PCR undetected on blood testing. From my prior reading, most Occult cases are identified by doctors from the elevated liver enzymes that are found on lab testing. When these individuals are given a liver biopsy, they are found to be HCV positive. It has been my understanding that Occult infection can lead to ongoing liver damage, and is found primarily in the liver...but not the blood, for some odd reason...It is an actual, active, ongoing HCV liver infection..nonetheless. These are usually untreated individuals (and often are previous IVDU's), who come to the attention of the medical community because of elevated LFT's.
Persistent Virus, on the other hand, I believe, is that form of remnant virus that has been detected by some researchers (Pham, Catillo, and others ) usually after SVR has been achieved. This 'remnant' form of virus, whatever it is (replicating controlled virus, or just maybe mutant viral forms, as HR implies) has also been found by these researchers in individuals who have spontaneously cleared as well. I think the "Persistent" label applies to this controversial, extremely low level , remaining "remnant" , NOT the same form of virus as described by doctors in their Occult research. The Occult form of virus is not controversial, and has been clearly documented by doctors and researchers. It may be less damaging, or maybe even JUST AS damaging to the liver as the typical chronic infection, but just fails to show up in the blood.
This has been my interpretation, regarding the two forms of virus, from all of my prior reading. I do believe that there is a difference between the two forms, as described by the medical experts. Using these two terms interchangeably clouds our understanding of what they mean.
DoubleDose
Occult HCV has often turned up in people who have no measurable blood infection, or those who are PCR undetected on blood testing. From my prior reading, most Occult cases are identified by doctors from the elevated liver enzymes that are found on lab testing. When these individuals are given a liver biopsy, they are found to be HCV positive. It has been my understanding that Occult infection can lead to ongoing liver damage, and is found primarily in the liver...but not the blood, for some odd reason...It is an actual, active, ongoing HCV liver infection..nonetheless. These are usually untreated individuals (and often are previous IVDU's), who come to the attention of the medical community because of elevated LFT's.
Persistent Virus, on the other hand, I believe, is that form of remnant virus that has been detected by some researchers (Pham, Catillo, and others ) usually after SVR has been achieved. This 'remnant' form of virus, whatever it is (replicating controlled virus, or just maybe mutant viral forms, as HR implies) has also been found by these researchers in individuals who have spontaneously cleared as well. I think the "Persistent" label applies to this controversial, extremely low level , remaining "remnant" , NOT the same form of virus as described by doctors in their Occult research. The Occult form of virus is not controversial, and has been clearly documented by doctors and researchers. It may be less damaging, or maybe even JUST AS damaging to the liver as the typical chronic infection, but just fails to show up in the blood.
This has been my interpretation, regarding the two forms of virus, from all of my prior reading. I do believe that there is a difference between the two forms, as described by the medical experts. Using these two terms interchangeably clouds our understanding of what they mean.
DoubleDose
This is not the exact article...but it still related...cant seem to find the other article
http://www.hivandhepatitis.com/hep_c/news/2009/020609_a.html
http://www.hivandhepatitis.com/hep_c/news/2009/020609_a.html
im looking now...it was posted here about 2 weeks ago...and it was a very recent article.
I have seen some reports of inflammation but I cannot recall seeing liver damage.
If you can find the article I would like to read it.
Mike
If you can find the article I would like to read it.
Mike
Sorry...i should have used "topic" instead of "delimma"....BTW...good info...i did see some study info somewhere that stated their was evidence of progressive damage to the liver because of the occult virus..alto the damage was on a much smaller scale and the study have a very small number of patients.
The following excerpt is form 2006 or perhaps earlier so, it is probably not accurate to describe occult HCV as new ["newness"]. The word "dilemma" suggests that there is proven harm or danger to "occult" or "persistent" HCV. I think that is overstating the situation. We should be careful not to alarm members when, as far as I know, there is, as yet, no fact based evidence for alarm.
Pham addresses the spontaneous recovery issue below.
Occult hepatits C virus persistence: identification and characteristics
By Tram N.Q. Pham, PhD, and Tomasz I. Michalak, MD, PhD
"....Lymphotropism of HCV
Although HCV is considered to be primarily hepatotropic,accumulated evidence clearly indicates that the virus also invades and replicates in the immune system. In fact, the presence of both HCV RNA positive and negative strands has been demonstrated in lymphoid cells in both in vivo and in vitro settings. For example, T cells, B cells, monocytes, and dendritic cells from patients with chronic hepatitis C have all been shown to carry HCV genomes.2,10-12 Most recently,by applying assays of superior sensitivity mentioned above, replication of HCV has been seen to persist in lymphoid cells for years after spontaneous recovery or a sustained virological response to IFN-alpha/Ribavirin therapy.1-3 In addition, low levels of HCV RNA in lymphoid cells have been detected in a significant proportion of patients with persistently elevated liver enzyme levels of unknown etiology.13,14 Along the same line, susceptibility of T and B cell lines as well as primary human T cells and macrophages to HCV infection have also been documented.15-18."
Mike
Pham addresses the spontaneous recovery issue below.
Occult hepatits C virus persistence: identification and characteristics
By Tram N.Q. Pham, PhD, and Tomasz I. Michalak, MD, PhD
"....Lymphotropism of HCV
Although HCV is considered to be primarily hepatotropic,accumulated evidence clearly indicates that the virus also invades and replicates in the immune system. In fact, the presence of both HCV RNA positive and negative strands has been demonstrated in lymphoid cells in both in vivo and in vitro settings. For example, T cells, B cells, monocytes, and dendritic cells from patients with chronic hepatitis C have all been shown to carry HCV genomes.2,10-12 Most recently,by applying assays of superior sensitivity mentioned above, replication of HCV has been seen to persist in lymphoid cells for years after spontaneous recovery or a sustained virological response to IFN-alpha/Ribavirin therapy.1-3 In addition, low levels of HCV RNA in lymphoid cells have been detected in a significant proportion of patients with persistently elevated liver enzyme levels of unknown etiology.13,14 Along the same line, susceptibility of T and B cell lines as well as primary human T cells and macrophages to HCV infection have also been documented.15-18."
Mike
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