Medical Forum / Diseases and Disorders / Hepatitis / November 2006
New paper w/ overview of occult Hep-c
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smith21347@msn.com - 17 Nov 2006 15:41 GMT http://www.wjgnet.com/1007-9327/12/6922.asp
Are people cured from hep-c ? I don't think so.
Ron
greyhackles - 17 Nov 2006 22:00 GMT >http://www.wjgnet.com/1007-9327/12/6922.asp > >Are people cured from hep-c ? I don't think so. And you are entitled to your opinion, no matter how demonstrably incorrect it may be.
Painting with broad brushes usually results in sloppy results...
/greyhackles
kjoh - 17 Nov 2006 22:22 GMT Hi Ron. This is a stinky rotten piece of news you posted. It sure weighs heavy on my thoughts about re-treatment. Findings like this have been floating around for a while, but nobody seems to want to make much of it (?). This isn't the kind of information that will make Roche and Shering Plough smile. What are the implications of these findings? Maybe this new "form" of geno 1b HCV RNA just hangs out quietly in liver tissue and peripheral blood cells and doesn't do a lot of damage. Or as much damage...
Here is a link and excerpt for a similar article from the same author(s). Notice that in both articles they are careful to point out that combo tx does improve liver damage.
Using the search window at www.pubmed.gov turns up lots of unreadable science. For example, type in "peripheral blood mononuclear cells + hcv" FYI, pubmed.gov is the U.S. National Library and National Institute of Health database of summaries from all major (and a zillion minor) peer-reviewed medical journals.
Also, I scrounged up a couple definitions in Wikipedia that might be helpful to people trying to make sense of these articles.
Not cheers kj 1b :-(
Hepatitis C virus replicates in the liver of patients who have a sustained response to antiviral treatment. November 2006 Clin Infectious Disease
"...Results: Positive-strand HCV RNA was found in 19 (95%) of 20 liver biopsy specimens, and negative-strand HCV RNA was found in 15 (79%) of the 19 samples that had positive-strand HCV RNA...Conclusions: HCV persisted and replicated in the livers and peripheral blood mononuclear cells of most sustained responders. Thus, these patients did not experience HCV infection clearance, despite apparent clinical disease resolution."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=17051492&query_hl=11&itool=pubmed_docsum
A couple definitions from Wikipedia::
"Peripheral blood cells are the cellular components of blood, consisting of red blood cells, white blood cells, and platelets, which are found within the circulating pool of blood and not sequestered within the lymphatic system, spleen, liver, or bone marrow...
A Peripheral Blood Mononuclear Cell (PBMC) is a blood cell having a round nucleus, such as a lymphocyte or a monocyte. These blood cells are a critical component in the immune system to fight infection and adapt to intruders. These cells are often extracted via centrifuge from whole blood samples for use in clinical trials...
An occult infection is medical terminology for a "hidden" infection, that is, one which presents no symptoms..."
http://en.wikipedia.org/wiki/Peripheral_blood_cell http://en.wikipedia.org/wiki/PBMC http://en.wikipedia.org/wiki/Infection
Thomas Wagner - 18 Nov 2006 01:46 GMT >Hi Ron. This is a stinky rotten piece of news you posted. It sure weighs >heavy on my thoughts about re-treatment. Findings like this have been [quoted text clipped - 4 lines] >peripheral blood cells and doesn't do a lot of damage. Or as much >damage... Well, I don't know. First of all, even the authors of the study clearly point out that this "occult" HCV doesn't do as much damage (if any) as normal chronic HCV. Second, it's not at all clear that HCV persists in ALL successfully treated patients. As we've discussed regarding similar previous reports, there are a number of possibilities:
a) what persists in (some of?) those who achieved SVR is not a "full-blown" HCV virus, but rather one that is severely crippled, as can be deduced from the fact that it doesn't replicate at any significant rate above barely keeping "alive". Given that practically all patients with SVR experience a significant and sustained positive effect on fibrosis and even cirrhosis, what remains of the virus obviously is pretty powerless to do damage. The incidence of cirrhosis and liver cancer in sustained responders is significantly reduced.
b) a small subset of patients achieving SVR may have remaining pockets of the virus in their system that are kept in check by the immune system, but could potentially rebound if there is a severe immune deficiency. Since there is no test that can prove the absence of the virus with complete certainty, this is certainly a possibility.
c) all of us who achieved SVR are ticking time bombs. This is simply absurd. There is no indication that any significant number of patients are in danger of relapsing 5, 10, or 20 years down the road. There have been a number of long-term follow-up studies, none of which found any such thing.
So... I don't know why the results of this study should keep anyone from initial or re-treatment. The authors found clear evidence of the treatment improving liver status. There is some conflicting evidence about viral persistence, and this should be investigated further. But there certainly is no reason to panic.
Thomas
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kjoh - 18 Nov 2006 03:40 GMT "But there certainly is no reason to panic."
Who panicked? It's just one more piece of information we must factor into our decisions. I do wish Big Pharma would step up to the plate and fund a few SVR biopsies and PBMC tests to help us figure out what this means.
Cheers kj
Thomas Wagner - 18 Nov 2006 05:29 GMT >>"But there certainly is no reason to panic." > >Who panicked? It's just one more piece of information we must factor into >our decisions. When Ron writes "Are people cured from hep-c ? I don't think so." then that sounds pretty panicky to me. And how is that information relevant to a treatment decision? Are you basing your decision on the word "cure" or on the clearly positive effects of treatment?
> I do wish Big Pharma would step up to the plate and fund a >few SVR biopsies and PBMC tests to help us figure out what this means. Since neither Roche nor Schering have ever used the C word, I'm not sure why they would be obligated to pay for this somewhat esoteric research. It's obviously being done, and somebody must be paying for it. But as the outcome of that research appears to have more psychological than physiological relevance (I don't care whether I still have a few crippled virions in me as long as they don't harm me) it doesn't look that high priority to me. There's more important stuff, like the development of better treatments, that they should be (and are) spending their money on. If against all odds we find out in 10 years that even folks that have been clear that long can relapse, I sure hope there will be better stuff available then.
Thomas
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kjoh - 18 Nov 2006 18:16 GMT "Well, I don't know. First of all, even the authors of the study clearly point out that this "occult" HCV doesn't do as much damage (if any) as normal chronic HCV."
Hi Thomas. Thanks for your input, as always. What the authors "clearly" point out is that the occult form of infection is a milder form of disease, but certainly not harmless or passive:
"...liver necroinflammatory activity and fibrosis were observed in a significantly higher proportion of patients with occult HCV infection than in those without intrahepatic HCV-RNA."
..Thus, it was concluded that occult HCV infection is a milder disease, with less liver damage than chronic hepatitis C. Nevertheless, as patients with occult hepatitis C may present dyslipidemic disorders, studies on the natural history of occult HCV infection should be performed to prove the role of occult HCV as the cause for liver injury in these patients...
..Therefore, it seems that occult HCV infection may play a role in the development of HCC however, as discussed above, more studies on this issue should be performed.
.. In summary, although these patients are serum HCV-RNA negative they could be potentially infectious as HCV is replicating in their PBMC, thus preventive measures to avoid HCV spread in hemodialysis units must be considered.
..Thus, patients with an occult HCV infection had a better immune response and this could be the cause of the milder disease that these patients have in comparison to those with chronic hepatitis. These results seem to suggest that the clinical differences observed between occult and chronic hepatitis C are a consequence of the host's immunological system."
This is important information, based on a growing number of studies. I am not panicking - I am not even hysterical :-) But I do find this information disturbing. I prefer not to cast it aside when I make my decisions about re-treatment.
Kathy don't shoot the messenger
Thomas Wagner - 19 Nov 2006 00:56 GMT >This is important information, based on a growing number of studies. I am >not panicking - I am not even hysterical :-) But I do find this [quoted text clipped - 3 lines] >Kathy >don't shoot the messenger No intention of shooting the messenger. However, please keep in mind that this study lumped all groups of "occult" HCV together. There are just two paragraph that pertain to the subgroup of sustained responders:
"Occult HCV infection has also been identified in a similar cohort of patients: those with chronic hepatitis C who have responded to an antiviral therapy with loss of circulating HCV-RNA and normalization of ALT levels. Several papers have reported the presence of an occult HCV infection (persistence of HCV-RNA) in the liver and in PBMC of sustained responders[22-24]. However, other authors have not found viral RNA in these patients[25,26]. These discrepancies could be due to different preservation methods of the liver biopsies, to differences in the sensitivity of the methods employed for HCV-RNA detection, different geographical incidence, etc. Thus, further studies are needed to know the real prevalence of occult HCV in complete responder patients. One of the possible consequences of occult HCV infection is the persistence of liver necroinflammation in an important number of sustained responder patients[23,24]. The case of a patient with chronic hepatitis C who cleared serum HCV-RNA with normalization of ALT levels in whom HCV infection reactivated following prednisone therapy after 8.5 years of HCV-RNA negativity has been published. Thus, occult HCV infection should be taken into account when these anti-HCV positive patients with normal ALT levels undergo immunosuppressive therapies[25]."
The references 23 and 24 are indeed disturbing (clickable pointers to all references are in the original article). But both looked at a very small sample. Reference 25 OTOH looked at 400 patients with SVR, and found viral persistence in just 2%. How those numbers can be reconciled is a big question.
But again, all this information must be viewed in the context of long-term mortality studies on SVR (and even "transient responder") patients. There aren't that many, but one is here: http://www3.interscience.wiley.com/cgi-bin/abstract/72513868/ABSTRACT
"This study included 594 patients with chronic hepatitis C who received interferon- therapy (Interferon group) and 144 patients with chronic hepatitis C who did not receive interferon (Control group). The patients in the Interferon group were classified into the following three groups based on the response of the serum aminotransaminase level of the patient during and after completion of the therapy protocol: sustained responders (n = 175), transient responders (n = 165), and non-responders (n = 254).
[Note: this was interferon monotherapy, hence the low success rates. More modern therapies could possibly also contribute to more persistent viral elimination.]
[...] Multivariate analysis showed that interferon therapy decreased the risk for developing HCC by 48% compared with that in the Control group [...] No sustained responder or transient responder in the Interferon group died of liver-related disease. The cumulative survival rates of the Interferon and Control groups were nearly identical during the first 5 years following diagnosis. Thereafter, the cumulative survival rate of the Control group declined, resulting in an 8-year survival rate in the Interferon and Control groups of 97% and 81%, respectively [...] Our study demonstrated that interferon therapy significantly lowered the incidence of HCC among patients with chronic hepatitis C who showed sustained normalization and among patients who showed transient normalization of the serum aminotransferase level after completion of interferon therapy. The survival analyses and determination of cause of death suggested that interferon therapy improves the long-term survival of chronic hepatitis C patients who respond to this therapy, possibly by decreasing mortality from liver-related diseases."
Sounds pretty good to me...
Thomas
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