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12 wk. UD & Genetics

Sep 06, 2009 - 4 comments

Bloodwork comes back a week before PCR results, but they finally got back with UD for my 12 wk. followup visit.  I had a very interesting discussion with the doctor.  He's pretty darn sure that the 12 week UD result will be switched in the treatment guidelines for the current 24 wk. declaration of SVR.  So many clear at 12 weeks stay clear.  Says that the odds of NOT maintaining a sustained viral response after a clear 24 wk. followup PCR are nearly zero. I think of the relapsers on the forum who relapsed months after the 24 wk. UD and I shudder.  They are the statistical small percentage that reacts contra to the guidelines.  How unbearably horrible that must be.

We also discussed the new biomarker for IFN response developed by Duke Univ. and partners.  He says it is one of the most profoundly significant discoveries ever.  I think they'll get the Nobel for it.  Press articles hypothesize (can't read the real article, it's only on Nature On-line - subscriber only) that an HCV-like virus swept through Asia and all those who survived it developed a genetic mutation that made their offspring immune (in that they could fight it off and destroy it if infected).  The mutated allele is right by the IFN manufacture allele.  The HCV-like disease crossed Europe also, but not to the extent of Asia.  Mutations passed along again.  Africa was barely touched by the disease; few mutations developed.

SOOOO, we inherit either a C or a T from each parent, making us either CC, CT or TT.  Lots of C parents in Asia, so 80% of offspring are CC, strongly responsive to IFN therapy to kill HCV.  Less parents in Europe (and european derived countries like US, Australia, NZ, Canada) since the disease did not hit so hard and alter the genes of as many as in Asia.  Poor Africa and their descendants only have an 18% or so shot of clearing the virus on IFN because they so often have the least responsive combo, TT.  The poor response of blacks to therapy is finally explained.  CT is a toss-up.  Might work out well, might not.

Schering Plough funded the genetics research.  I sent a DNA sample myself as part of a study.  They own the intellectual property for the discovery so they will determine who will develop and market the screening test that will be a 3rd genetic component of pre-TX screening, like genotyping and PCR's.   I imagine that all will be screened and those who come out CC will be treated with IFN/riba and for a shorter time.  Those who come out otherwise will be treated with triple therapy and not made to suffer through IFN/riba alone with only a chance of success and the possibility of developing anti-IFN antibodies.  It's a new world all of a sudden.

I'm fascinated with it because I had such a bizarre response to therapy.  I had acute HCV when I was a teenager and assumed I cleared the virus.  Not so.  I lived with it unknowingly for 38 years(!) then it cropped up after a year of naproxen sodium use for a bad back had caused cirrhosis.  In a panic, I jumped into a trial, involving 4 wks of IFN/riba followed by 24 wks of additional protease inhibitor.  They were very clear with me initially that cirrhotics did not respond well.  I had no reaction at all to the shots.  Doctor scared me by saying that might mean that I was not responding to the IFN.  Abject misery until the bloodwork (taken that day) for the 1 wk. PCR came back.  Undetectable.  The doctor was stunned.  How could this be that a cirrhotic cleared in 1 week with only IFN/ riba?  I remained UD in spite of continuous IFN reduction.  Not just RVR, but URVR.

I searched for an explanation.  I did find a reference about 1b's with low VL clearing early and easily.  I was 1b and had a VL of 275,000 at day 1.  Now I know it was more than that and I was lucky enough to be born with the right genetic polymorphism (that's a mouthful); that my outcome was never in doubt.  I started TX Nov. 14 and the science has changed many times in just 10 months.  They now know that maintenance IFN cannot defeat advancing fibrosis, that extended treatment is probably not beneficial, that there is a genetic cause to response to IFN. May you live in interesting times.

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233616 tn?1312787196
by merryBe, Nov 01, 2009
I've never seen a yellow magnolia, how cool, I want one!!! I'm relandscaping my whole property!! Good for my morale!!

mb

338734 tn?1377160168
by IAmTheWalrus, Nov 02, 2009
Very interesting! Looks like I was an idiot for going the marathon 86 weeks, but it did seem to halt and even reverse the fibrosis progression if only temporarily.  At least I relapsed at 12 weeks and not post 24.

B

717272 tn?1277590780
by newleaf09, Nov 03, 2009
Advancing science is going to make idiots out of all of us.  I imagine that in 10-15 years everything about curing HCV will be cut and dried, not the horrible challenge it is now.  It's all moving so fast suddenly which is certainly a good thing, but all us early guinea pigs are going to end up with very mixed feelings.  Everthing could always be worse.  I visited a historic hot springs and saw the tub where they originally gave mercury baths to treat syphilis.  Great!  Die of mercury poisoning instead of syphilis.  Now it's just a shot of antibiotic.  Given time, HCV will probably have a similar story.  Sure hope so.

Avatar universal
by carol411, Jun 21, 2010
Wow!  This is wonderful news.  I'm a dumpling shaped woman who did not find out til already treating that my body mass could adversely effect my chances of clearing.  Now it's not my shape but my genes that is going to determine the outcome.  Joy!!!  I don't know how I found this, but you have made my day!

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