New occult paper

"Occult Hepatitis C Virus Infection among Hemodialysis Patients."

(from the paper):

"Occult hepatitis C virus (HCV) infection (i.e., detectable HCV-RNA in the liver or peripheral blood mononuclear cells) in the absence of both serum HCV-RNA and anti-HCV antibodies has not been investigated in hemodialysis patients. In this study, real-time PCR and in situ hybridization was used to test for the presence of genomic and antigenomic HCV-RNA in peripheral blood mononuclear cells of 109 hemodialysis patients with abnormal levels of liver enzymes. Occult HCV infection, determined by the presence of genomic HCV-RNA, was found in 45% of the patients; 53% of these patients had ongoing HCV replication, indicated by the presence of antigenomic HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on hemodialysis and had significantly higher mean alanine aminotransferase levels during the 6 mo before study entry. Logistic regression analysis revealed that mortality was associated with age >60 yr (odds ratio 3.30; 95% confidence interval 1.05 to 10.33) and the presence of occult HCV infection (odds ratio 3.84; 95% confidence interval 1.29 to 11.43). In conclusion, the prevalence of occult HCV infection is high among hemodialysis patients with persistently abnormal values of liver enzymes of unknown cause. The clinical significance of occult HCV infection in these patients requires further study."



The above paper has been added to the MedHelp "Occult Health Page" - http://www.medhelp.org/health_pages/Hepatitis/Occult-Hepatitis-C/show/54?cid=64


TnHepGuy

[mikesimon]

Thanks for that. Mike

[DoubleDose]

This article illustrates why I believe Occult and Persistent HCV are two entirely different entities.  The Occult form seems to affect the liver, and generally produces high LFT's.  It also seems to occur in hemodialysis and IVDU's at a fairly consistent rate, and seems to have a known origin...it just fails to infect the blood, and produces no serum antibodies.  That is pretty strange viral behavior, but it has been well documented over the years, and is one of those unexplained phenomena.

The persistent stuff  (Warning!   Disclaimer!!!!!  That is, if it ends up being real, and is really reproducing!!! Disclaimer) - is a different entity, and seems to occur AFTER SVR or spontaneous resolution, and can be found in various cells and systems, but only at very minute, sub-detectable levels.  This persistent virus seems to be some sort of 'after-occurrance' when the active HCV viral infection resolves, and the person is considered SVR or no longer infected, by PCR.  The tests done to identify persistent virus, are beyond the scope of standard PCR testing, thus I use the term 'sub-detectable'.

I only mention this, to prevent confusion among those reading our commentaries about either persistent HCV or Occult HCV.  I believe they are discrete and different entities.

DoubleDose

[TnHepGuy_]

In the past I have wanted to sub-divide occult into two differing types of low-level infection (and that certainly could end up being the case about it when all is said and done). But I've since decided that there is so little out there now beyond the basic research being done, that the definition used in the abstract above ("detectable HCV-RNA in the liver or peripheral blood mononuclear cells"), though broad, works just fine. Until they are able to find any molecular difference (or not) between the two RNA viruses (primary occult vs. secondary (i.e. - post-SVR/post-spontaneous clearance occult) I'll accept the all-inclusive version. If it's good enough for Castillo, Pham, et al for now - that's enough for me.


TnHepGuy

[DoubleDose]

I agree with your take to an extent.  But the only real difference that I see, that is noteworthy, is that generally the references to Occult virus seem to be characterized by an actual active, chronic infection in the liver, that also produces abnormal LFT's, and I assume, is also producing ongoing, measurable liver damage.  So far, the Persistent virus, generally seems to be more benign, and does not cause any noticable liver abnormalities, nor major health consequences that anyone has been able to tie directly to the persistent infection.  I think that is a big enough difference to warrant a distinction between the two entities, or at least an * asterisk, until there is a clearer understanding of the relationship.

Not to quibble, but just trying to be clear on MY read on what the research seems to suggest for Occult vs. Persistent.  It may not make much difference, and they may all be from the same origin, but I see a difference in 'consequence and danger' between the two.  Also, do you believe that the researchers, in their comments and articles regarding "Occult HCV" are confirming the absolute existence and validity of "Persistent HCV", which some on this forum, vehemently refute?  If so, then the argument against Persistent Virus is a non-argument, since almost all top Hepatologists and mainstream HCV specialists are aware of, and accept "Occult HCV" as fact. It has been clinically observed, studies, treated, and written about extensively, even if not understood.  I am still not fully sure if they are equivalent.

DoubleDose

[TnHepGuy_]

I just took another look at this Carreño summary paper:    http://www.wjgnet.com/1007-9327/12/6922.asp     and he does make the categorical distinction you describe:

"..... occult infection can be present in two different clinical situations: in anti-HCV negative, serum HCV-RNA negative patients with abnormal liver function tests and in anti-HCV positive subjects with normal values of liver enzymes and without serum HCV-RNA."


He goes on to say (in the section labeled 'OTHER FORMS OF OCCULT HCV INFECTION'):

"....occult HCV infection is characterized by the absence of anti-HCV and of serum HCV-RNA, but viral RNA is detectable in liver and PBMC. However, occult HCV infection may exist in other clinical situations such as in anti-HCV positive patients who are serum HCV-RNA negative and who present normal liver function tests. One of these populations is the “healthy” HCV-carriers. These patients, who are anti-HCV positive with undetectable serum viral RNA and normal ALT levels, are considered to be subjects who have cleared HCV infection after exposure to HCV."

and,

"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."


So, he's using two categories, while also possibly further dividing the secondary occult patients into two sub-categories: post-spontaneous and post-SVR's.


As far as secondary occult/persistent not causing any liver abnormalities, he writes: "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]."

And he references Pardo     http://www3.interscience.wiley.com/journal/118000831/abstract?CRETRY=1&SRETRY=0     when comparing the types of infections between chronic and occult and concluding that occult is a more benign form. Here the abstract suggests the patients chosen were primary occult carriers ("HCV-RNA in liver in the absence of anti-HCV and serum HCV-RNA").


One thought I have is: could there be a population of primary occult carriers who are absent anti-HCV and serum, yet have NO elevated LFT's? Since we are talking about possible liver bx PCR and/or PCBM amplification techniques to determine this population (assuming it exists), it is doubtful that any researchers will be scouring the general population asking any-and-all comers if they'd like a bx, even though they've show no testing to justify one.

Another question that comes to mind is: can occult be transferred (i.g. - transfusion, IV drug use, etc) and remain an occult infection in the new patient - never reaching chronicity? This also touches on the subject of primary occult carries: could they be anti-HCV because they have cleared the anti-bodies as well as any chronic infection (therefore, being left in the category of occult carriers)? Or, could have a certain percentage of them never reached full-blown HCV infection and always remained at occult levels? Though this scenario would likely point to a huge prevalence among transfusion carriers of not only of occult Hep C, but also occult Hep B and any other virus that would fall into the "occult" category - and I don't know if researchers are coming up with anything like this in that population.


TnHepGuy

[DoubleDose]

Those are all great questions, and point up the great complexity of this "occult" subject.  There is much mystery surrounding occult, and the prevalence in the population can only be abstractly guessed at.  Who knows what sort of 'carrier' classes might exist out there, and as you mention, without obvious markers or red flags, who would ever know if these people harbor a silent liver infection, or other possible forms of occult HCV, minus the serum markers???

What I think we are seeing, in regard to the quoted comments that you provided, is a tendency to sub-divide the 'categories' of occult infection, and to try to look at the 'whys and  hows' of both, or all three manifestations.  When I read the above comments and research findings, and then consider how absolutely 'black and white' many medical professionals and laymen want to characterize HCV infection, I am taken aback.  There is just SO MUCH that remains unexplained, and that does not fit the nice neat model of either absolutely "Eradicated and Gone", by PCR verification, OR on the other hand, "Absolutely Infected".  These two categories hardly cover the spectrum of infection, test results, and little understood, atypical infection patterns that we now regularly read about.  That's why I don't subscribe to neat little 'pat' answers on Cure and Eradication.....at least not yet!  These clean little 'either-or', absolute answers fly directly in the face of growing clinical and research observations.
More to come I am sure.  Thanks for your clarifications and referencing.  Your illustrations are always a welcome addition to our knowledge base.  You tend to bring the specifics that we all want to see.

DoubleDose

[Jacob43]

Quite a read, and interesting to see this type of discussion