Likda K's Thread cont/hepatitisresarcher/Willing/Ina/Others

[jmjm530]

Willing: Perhaps this seems like quibbling over many RNAs fragments can hide on the head of a pin
---------------------------------------------------------
Probably more HCV RNA on the head of a "needle" as opposed to "pin" per the Talmudic expression :)
-------------------------------
Anyway, Thought I'd open this up to continue the interesting dialogue with hepatitisresearcher and others. Hopefully, Linda K's original question got answered along the way :)

[Eisbein]

I apologize, above sentence should have read:
When I asked my doctor if it would be a good idea.....
                

                       and NOT      

When I asked my doctor if it wouldn't be a good idea...

Ina

[jmjm530]

To clarify, I was talking about the seeming inconsistency of serum HCV RNA being stable over time versus the inherent variability of the HCV RNA assays per M. Shiffman's presentation. Those two values I gave were my pre-tx values unaffected by any decline caused by the tx drugs suggesting HCV RNA instability over time. Like yourself, I also found the Stalingrad analogy apt especially in regard to the "poisoned food". Comparing ribavirin to poisioned food is a metaphor anyone who has treated can well relate to! That said, I certainly hope HR is wrong in the respect that newer
non-riba based therapies (see C7)may not result in SVR. We will have a first look within the year as data from the non-riba VX 950 SVR arm(s)rolls in, and other looks down the road if/when different protease inhibitors are combined in some sort of cocktail approach, and/or when other non riba based approaches are tested down the road. If I remember correctly, your biopsy reads sounded fairly consistent so I guess I will declare myself the winner with 5
reads:) BTW I hope you weren't suggesting they mount your entire liver on a slide.

Be well.

-- Jim

[Eisbein]

you said:
Well you could also interpret this result simply in the sense that under IFN many lines of the virus died out and only a few strains with a genetic makeup fit to survive under these harsh conditions survived.

I used to call these strains that survived King Kong viruses, or super bugs.
When I asked my doctor if it wouldn't be a good idea to bombard any hidden King Kongs at the end of tx with higher doses of Peg for a couple of month, his answer was "YES". But only the Interferon, not upping the Riba he added.

I was too sick at the end of tx to double up on the Peg, but I surely wanted to.

Any comment on my docs suggestions.

Ina

[willing]

the analogy between a death march and long-duration combo treatment seems very appropriate! (though in thise case I guess it's the dwindling group of virions who have to keep putting "one foot after the other").
Presumably there is something to be learned by analyzing the genomes of the "survivors", which is why the phylogenetic analysis in Castillo would seem to be promising. Long-lasting serum-UND must result from some combination of decreased viral production and increased host clearance. Is it too simple-minded to expect to see evidence of the former by changes in the genomes of the survivors?

Anyway, yet another topic I'd be interesting to hear your thoughts on, and which relates to Ina's question is HCV cell specificity. Recently <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=16618405">Pal'06</a> made the  remarkable claim that, in one case of HCV infection they analyzed, more serum virus was genetically similar to lymph-resident virus than to liver-resident virus. This claim was quickly challenged, including a  letter  (<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16901578&query_hl=6&itool=pubmed_docsum"> Dahari'06</a>) by Neumann and Perelson who I think of as the founding fathers of HCV kinetics. Do you think the findings are credible ? Is it possible for HCV replication outside the liver to be that significant?

Jim : I think it must be tripping over the math again. The  <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9756471&query_hl=9&itool=pubmed_docsum"> Neumann/Perelson equation </a> is a simple first-order ODE; you just needed to bring your calc book with you when you took the VL test...

[jmjm530]

Rev: (The durabiity of SVR) is an open debate both here and among medical science.
=======================

I know we've covered this ground before but maybe not for Jay's benefit. According to recent studies, SVR is durable 5-10 years out.

They don't have statistics further out than that so that's where the 5-10 years comes in.

Your position as I understand it is how do we know it will stay durable beyond 10 years. My position is that there is no evidence that it won't remain durable beyond ten years.

Hopefully I'm not putting words into your mouth, just trying to clarify the issues here both for Jay and myself.

That said, I think Jay is more concerned about the "persistent" issues put forth by HR and Willing, i.e. where virus may be detected in some compartments after SVR even when standards tests show one is non-detectible.

-- Jim

[willing]

please ignore my comments above about Schiffman's estimates of VL variability being based on older data; I'm wrong. The most recent update of his review on treatment those who fail tx <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16527652&query_hl=21&itool=pubmed_docsum">Shiffman'06</a>
puts it at "The accuracy of the commercially available HCV RNA assays is reported to be ±0.5 log units " and cites <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11682522&query_hl=24&itool=pubmed_docsum">Shiffman'01</a> as support.