New Occult Hep C paper from Pham et al

[TnHepGuy_]

Chronic hepatitis C and persistent occult hepatitis C virus infection are characterized by distinct immune cell cytokine expression profiles.

"Hepatitis C virus (HCV) replicates in immune cells in both chronic hepatitis C (CHC) and occult HCV infection, but the extent of virus replication in this compartment in these opposing infection forms varies greatly. It was unknown whether this could be linked to HCV genotype or to differences in host gene expression shaping the immune response, and whether HCV replication in immune cells is sensitive to endogenous antiviral cytokines. In this study, we uncovered that significantly greater HCV load in peripheral blood mononuclear cells (PBMC), but not in plasma, coincided with HCV genotypes 2 and 3 in CHC, but with genotype 1 in residual occult infection after clinical resolution of hepatitis C. Moreover, PBMC from individuals with occult infection transcribed significantly greater levels of IFN-alpha, IFN-gamma and TNF-alpha, but less interleukin (IL)-10 than those from CHC. In CHC, PBMC with low HCV load expressed significantly more IFN-gamma but less IL-12 than did cells with high virus content. In occult infection, HCV RNA detection in PBMC was associated with much lower IFN-alpha and IL-12 expression. Further, HCV replication in T lymphocytes could be completely eliminated by activation of endogenous IFN-gamma in CHC, but of IFN-alpha in occult infection. In conclusion, CHC and persistent occult HCV infection are characterized by clearly different profiles of antiviral cytokine response in circulating immune cells which are also different from those of healthy individuals. Higher expression of IL-10, combined with lower transcription of IFN-alpha, IFN-gamma and TNF-alpha, is associated with a more robust HCV replication in immune cells."

http://www.ncbi.nlm.nih.gov/pubmed/19215578?ordinalpos=1&itool=Email.EmailReport.Pubmed_ReportSelector.Pubmed_RVDocSum


TnHepGuy

[Rockerforlife]

Im pretty sure a large % people who SVR will go on to live normal lives...providing they dont go on and party like its 1999....my nurse says in her 28 years of treating patients that all are still SVR...and in good health...who knows if the "occult patients,"  (who show the slow  progression of damage) is not caused by life style or even things we dont even know...just my thoughts....ill take the SVR  if a can and from then on....just do the regular check ups for damage...to me im not too worried about no occult bug....yet

[DoubleDose]

HR, thank you very much for your clarifying comments on this research study.  I also concur with your conclusion, and feel that this post-SVR, cytokine reaction to the now suppressed, persistent virus after SVR, may just be the missing link in our pursuit of just what causes so many post-tx, long term after effects.  Certainly the Interferon itself may be responsible for a good portion, but my contention is that much of the ongoing, and often 'auto-immune' in nature responses that many of us experience, is exactly this phenomenon...a post-tx cytokine response to low level virus.  So we are SVR, but still a little like smoldering coals....or maybe like radio-active, half-life victims....  Thanks for being a part of the forum again!!!

TnHepGuy - Thanks for your follow up questions and comments regarding HR's reply.  I also second your questions!!!  This subjest still deserves much attention, and not to be 'blown off' by those that would prefer to assume that it is a very benign phenomenon...or even a non-existent issue.

DoubleDose

[TnHepGuy_]

Very good to see you here again!  And thanks for taking the time to comment on this paper.

"My note; this is further evidence that in some SVR this ongoing innate immune stimulation will have the consequence of increased inflammation, over the level that this person would have had, as a simple age related phenomenon, if never HCV infected. There is not much that can be done about this. It most likely serves to stabilize SVR."


As 'mikesimon' mentioned above, and what you have stated, this is the practical 'crux' of any discussion re occult: the potential negative effects of having an ongoing immune response to replicative RNA. The price some (all?) SVR's may have to pay to remain so is a chronic increase in their immune system - but at what cost?


So I would ask you (HR) this:

- In general terms, what are the known clinical consequences of patients w/ similar such long-term conditions (i.e. - chronic over-stimulation)?

-  Increases in autoimmune concerns?

-  A lowered or lessened ability of the immune system to properly respond when called upon to do so?

-  Would it be a reasonable assumption that in this particular type of chronic immune response (to occult Hep C) a fibrotic response would not be unusual?


And while there may not be much that can be done in regards to having and 'treating' an overly stimulated immune system, I believe a patient in such a circumstance benefits greatly when knowing what their current condition truly is. Such knowledge can eliminate unnecessary testing, false diagnoses and wrong treatments to symptoms and ailments that might otherwise be incorrectly attributed to unrelated sources.


TnHepGuy

[Rockerforlife]

Although occult HCV infection generally appears to be mild, some patients have shown evidence of serious chronic liver injury. In addition, occult infection raises the possibility of disease spread via blood donations, hemodialysis and other procedures. Fortunately, the study also suggests a minimally invasive approach to detect occult infection.


http://www.innovations-report.com/html/reports/medicine_health/report-24439.html

[Hepatitis Researcher]

here is the conclusion of the authors;

In summary, our study revealed that HCV replication in lymphoid cells in CHC and occult persistent infection is accompanied by evidently distinct expression profiles of the genes involved in antiviral and proinflammatory cytokine responses. Expression levels of some of the genes were found to be closely related to the virus loads in circulating immune cells.

The fact that the gene transcription profiles in low-level HCV infection were different from those of healthy individuals also argues that the virus replicating at low levels in immune cells is not ignored by the cell innate defence but continues to trigger its response for many years after clinically apparent clearance.

Further work is required to determine whether the status of virus replication in immune cells and the expression profiles of the genes induced, including those identified in this study, could serve to predict the patient's response to antiviral therapy and the likelihood of establishing CHC.


My note; this is further evidence that in some SVR this ongoing innate immune stimulation will have the consequence of increased inflammation, over the level that this person would have had, as a simple age related phenomenon, if never HCV infected. There is not much that can be done about this. It most likely serves to stabilize SVR.

[mikesimon]

The title of the article and it's conclusion pretty much sums it up - that occult hep c and chronic hep c have different cytokine expression profiles.

Chronic hepatitis C and persistent occult hepatitis C virus infection are characterized by distinct immune cell cytokine expression profiles.
                                              
"In conclusion, CHC and persistent occult HCV infection are characterized by clearly different profiles of antiviral cytokine response in circulating immune cells which are also different from those of healthy individuals. Higher expression of IL-10, combined with lower transcription of IFN-alpha, IFN-gamma and TNF-alpha, is associated with a more robust HCV replication in immune cells."

It's relevance to us is probably purely academic. This article assumes that persistent occult hepatitis is real. We can and have argued about the issue of whether occult hepatitis truly exists. But the topic most vigorously discussed/debated has been: if it does exist what does it mean for SVRs in terms of liver health - ongoing damage -  and health in general and is there the possibility of recurrence or re-emergence of detectable virus.

My personal opinion is that SVR is durable and confers a great benefit and may improve liver histology. I think that is pretty well settled..
For my purposes anything beyond that is purely academic. I suppose it's nice to know that the anti viral cytokine response in immune cells are different for CHC and occult hepatitis but I don't really know what to do with that information

Mike