Dual genotypes and lots of confusion

[Bill1949]

Hi My name is Bill and it is nice to check this forum out again.
Maybe you can help with a couple questions. About 2 years ago I was diagnosed with Hep C with type 2b and 150,000 viral count.  I went on the treatment and I admit I had a Gastro who wasn't very good.  After 8 weeks I was down to <50 VL. It stayed that way until at 22 or 23 weeks he took me off because I had a rash
on my chest.  As you figured, after 2 months off it was back to
1,500,000 VL. I decided to see another Gastro after moving to Florida.  Last week I had a liver biopcy and complete blood test.
This time Quest, the same lab as before came back that I am a 1a and a 2b.  I have never heard of a dual genotype. I was stage 3 and 3 something else. My alt and ast were 43Ast and 62 Alt.  That is about what its been since about 2002.  By the way I must have had the Hep C 30 or 35 years.  I don't have any complaints but brain fog.  That could be because since the Peginterferon and
Riba, my platelets have been in the 115 to 118.  Though its going up little by little.  The 1a has kinda shaken my world.  What do you guys think.  Has anyone heard of a dual genotype and the platelets being down. The next thing is to try to get my medicare insurance to pay.  The last one didn't and I got it from the Manufacturer. Now with income of $3100 a month for a married couple may be do much.  I haven't gone to the VA in Tampa
because I have been trying to get Botox for Bells Palsy for 8 months and nothing yet.  I think going to the VA may take longer than mere mortals have. Please any advice would be great.  Bill1949

[jmjm530]

Well there a couple of explanations --

First, one of the geno tests might be wrong. I'd re-test a third time to sort this possiblity out.

Second, you may have been 2b the first time and then got re-infected with the 1a strain between the two tests, especially if you've had any unsafe activities or blood contact.

I'm not sure, but I've heard that one strain will eventually dominate but maybe that takes time, which would account for two geno's appearing at once.

Unfortunatly, if this is the case, I assume you
will have to treat as a 1a, which of course has a longer course.

Given your stage 3 status, you should really consider re-treating right away after first being completely evaluated by someone who specializes in liver disease.

[hep62pj]

Speaking of confusion:

I have had 3 genotype tests and they all came back the same "hybridization pattern for this HCV amplification product is atypical and cannot differentiate between HCV types or subtypes". So I guess I am a mutant genotype haha or maybe a new one. The dr's all think this is very strange, in fact they all said lab error but have pretty much given up trying to type me after 3 tests all said the same thing...

I treated for 6 months on virimadine on a phase III trial but meds were discontinued becuz they said I did not have enough of a decrease in v/l. Since it was a double blind trial, they have not release any info about my levels if they went down at all or not, I have a personal appt with one of the clinical trial dr's and hope she can get this info for me.

I feel very alone ... I have posted about this on a few other hep boards and have not found anyone else in this situation regarding genotype on other boards either... which is pretty scary for me becuz I feel my chances of getting rid of it are pretty much zero if they do not know what type I have.

[Bill1949]

I just want you to know I will be perfectly honest with you guys.
I haven't had sex with anyone but my wife in 32 years, plus I haven't touched illegal drugs since 1992. No transfusions, coke, tattoos, or anything since finding out about my hep in 1992. Can a person actually have 2 genotypes?

[jmjm530]

If I had to guess -- based on what you just said, and your failed prior treatment -- I'd say the first genotype test was wrong and you did have a dual genotype back then.

If in fact you were a single genotrype 2b on your first test, the odds strongly suggest you should have cleared the virus even with 22 or 23 weeks of treatment. Especially with your EVR at week 8.

You really need a third genotype test to confirm and then speak to a heptologist regarding options.

[willing]

to make sense of multiple/ambiguous HCV genotypes you have to delve into the details a bit. The HCV genotype is only about 9500 nucleotides long, compared to about 3.2 billion for us. In this little fragment of RNA are encoded the <a href="http://hcv.lanl.gov/content/hcv-db/MAP/landmark.html">blueprints</a>  for making all  proteins required to make more copies of the virus(these proteins have names like E1, E2, NS1, NS4b, etc).  Whereas human genomes are around 99% identical, the differences between HCV genomes are MUCH greater. This is primarily due to the fact that the protein that makes a copy the HCV RNA (the RNA polymerase) makes lots of mistakes, so a "child" can end up with a very different sequence than its "parent". To deal with all this variability, researchers have grouped different HCV sequences into different "genotypes" (1,2,4..)which are about 60-70% similar and "subtypes" which resemble each other more closely.  As HCV continues to spread and is studies more closely, the number of groupings keeps growing. One of the best current databases of hcv sequence is at <a href="http://hcv.lanl.gov/content/hcv-db/classification/genotable.html">Los Alamos Labs</a>.

When you get a genotype test they should, in principle, obtain the entire sequence of your virus and compare it to the known  databases to see what  type it most resembles. They don't, because this is too expensive. Instead they snip off about 222 nucleotides and run hybridization tests that match your snippet against known templates to get a classification. This  is known to work *most* of the time (see a recent <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15483230&query_hl=11">review</a> by Simmonds who came up with the first classification rules) but there's always exceptions. If the run-of-the mill genotyping test isn't working for you, you should contact a specialist who can look at the test in more detail (eg a univ. lab can do the sequencing and the Los Alamos database is now looking for unusual sequences, see <a href="http://hcv.lanl.gov/content/hcv-db/index">news</a>). For treatment all you really care about is whether your virus looks more like a 1 or a 2-3).

Infection by multiple strains is well documented (see <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15850474&query_hl=17">for example</a>. During infection one strain dominates, however, after tx and relapse the dominant strain can change (I remember seeing a paper that described a switch of this sort, but I can't find it right now - maybe some one will remember it).

[susan400]

I am a 1A and a 1B.  The lab, a reputable one, said that I had two separate strains, a 'mixed virus'.  There's been other people on here that had dual genotypes, so it's not unheard of.

Susan

[cuteus]

it looks like they are looking for samples, hep62pj, maybe they will name one after you!

I think Willing has mentioned his line of work before, but I forgot many things...it has to be in the science field for sure, right? Interesting sites!

[Gladitsnotworse]

My genotype came back 1a/b cannot differentiate from Quest.

[chellski]

weird about your test results - i guess like jmjm said i would see about retesting for geno type....good luck with everything else - good to see you posting....
michelle

[hep62pj]

Willing thanks so much for the info, now I don't feel so strange anymore hahaha yea right

FYI all 3 of my tests were also done by Quest...

I was treated on clinical trial for virimadine as a type 1, I am making an appt with the dr's at the hospital there to find out where to go from here, since they stopped the meds after 6 months becuz I did not respond or did not respon enough, don't have any more info right now but I am hoping the dr can get it from the drug company who sponsered the trial...maybe I will talk to her about another genotype test...

Thanks everyone for replies!!

[Bill1949]

I will ask my Gastro to see about another test. If he does I wonder if I should go to Quest again or another Lab. Believe me when I say this, that it is not rubbing salt into an open wound to those with 1a, but I sure hope it is 2b. When I heard a couple years ago that I had genotype 2b,I thought except for having a great wife,wonderful daughter and knowing the Lord Jesus, that I usually don't luck out like this. I better start thinking more positive. Bill

[willing]

hpe62pj: Quest's <a href="http://www.questdiagnostics.com/hcp/intguide/jsp/showintguidepage.jsp?fn=TS_HCV_RNA_GenotypeLiPA.htm">genotyping test</a> uses sequence from one end of the HCV genome (the 5' UTR in the "blueprint" link above). Another test that looks at this same region is TRUGENE, sold by Bayer. <a href="http://jcm.asm.org/cgi/content/full/41/10/4855?view=long&pmid=14532242">Comparisons</a> of the two tests seem to favor TRUGENE, so it might make more sense to try that than to repeat Quest's test. Another alternative would be to use a test that uses a different part of the genome. The NS5B sequence has been successfuly <a href="http://jcm.asm.org/cgi/content/full/43/2/733?view=long&pmid=15695672">used for genotyping</a>. I don't know a lab that has offers this but your Dr. might be able to find one.

Bill:in your case it's not an issue of the test not matching a known genotype but of it detecting infection by two genotypes. I think trying the more sensitive TRUGENE test would provide more information than repeating Quest's LIPA test: if the type 1 infection is a test error it's less likely to show up in two different types of tests.

[jmjm530]

Very interesting stuff from Willing -- and I know you don't want to be a 1a --  I mean who does. But in terms of future treatment, regardless of genotype, you have to reconcile yourself to at least a 48-week course, given the fact that you're at least a stage 3, and have already relapsed at what was almost the standard 24 weeks for geno 2. And if it does turn out on re-testing you're a geno 1, then you have to seriously consider extended treatment beyond the 48 weeks.

Hopefully, the re-testing will clarify things moree. But if the 1a comes up again,or if the test is inconclusive, you should prbably err on he side of caution and consider yourself a 1a for treatment purposes.

Let us know what happens.

-- Jim

[Bill1949]

Thanks to all of you who responded.

[hep62pj]

Yes thank you all Very Much *especially* Willing!!  I have been stressing about this for awhile, posted before but never got much info from anyone.

Thanks again

[willing]

you're welcome. BTW, here's a contact for <a href="http://www.hivresistanceweb.com/protected/testinfo/tables/visgen.shtml">Visible Genetics</a> the company that developed TRUGENE and has since been bought by Bayer. They should be able to point you to a local lab. It looks like their HIV genotyping kit has been FDA approved but the HCV test hasn't (yet?). Hopefully this won't be a problem (most commercial HCV quantification tests also aren't FDA approved).