confused - HCVneg or positive? pls help!

I need help please. Several months ago, I had, I think, 2 needlesticks on separate occasions (I'm a nurse in egypt). I had a test for HCV around 4 weeks after the last accident and it was negative. Then the other day, I again had a test which yielded positive (on PCR). I was so distressed I did another test at a different hospital on the same day, this time I was told it's a 3rd generation test, and found out a day after that it was negative, the result 0.27 S/CO (with the reference range up to 1.0 S/CO negative). The lab tech wasn't around to explain to me what that means or even what S/CO stands for, as I picked up my results late and the clerk was just as clueless. Does having 0.27 S/CO means I have some antibodies running through my blood, or that doesn't mean anything at all? I plan to do another test at yet a different hospital, but while waiting to do that, I'm in desperate need of a definite answer. I can only put my hopes in a wonderful God. Thanks so much!

[Bill1954]

Hi Mindoza

If you tested positive for HCV using PCR technology, then you shouldn’t require any more EIA antibody tests. The early stage of HCV is known as ‘acute’ infection; my understanding is that until seroconversion occurs, PCR results might not be 100% specific.

My thoughts are to wait for 90 days or so to ensure seroconversion, then retest with ‘HCV RNA by PCR’.

Good luck to you—

Bill

[mindoza]

Thanks Bill for answering, and wishing me luck. There has been five months after that first test which was negative, and now this positive with PCR. What about those values for the 3rd generation HCV antibody test that I did? Which test is considered the confirmatory test? I'm sorry I came back with more questions, I can't discuss it right now with some doctor where I work because of the issues that come with it, I'm sure you understand. Thanks again!

[mikesimon]

S/CO stands for signal to cutoff ratio

From:  Anti-HCV Signal-to-Cutoff Ratio in Predicting Hepatitis C Viremia

"....One of the simple methods is sample
Signal-to-Cutoff (S/CO) ratio of anti-HCV immunoassay.
So the Center for Disease Control and Prevention (CDC)
published guidelines that recommended supplemental
tests to be based on anti-HCV assay S/CO ratios [2].
Generally, the S/CO value of more than 1 is regarded as
positive in CLIA test. However, owing to improvement in
the sensitivity of HCV tests, it is suggested that more
accurate standard for reflecting positive HCV infection is
needed. Thus, establishing optimal S/CO ratio is
prerequisite for avoiding unnecessary further HCV tests
which are currently adopted for increasing the reliability
of diagnosis. In this regard, S/CO ratio is thought to better
reflect HCV infection status of patients...."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784971/pdf/kjim-24-299.pdf


Mike

[Bill1954]

Yes, I do understand completely.

There are no doctors here; you should be aware of that as well. We are patients that hae dealt with HCV in the past, or are dealing with it now.

You have a rather unusual situation. The very low Sc/o (signal to cut-off ratio) result would lead one to believe you were not infected. However, the PCR is considered *very* specific for active RNA infection in established, chronic infection.

However, in early acute infection (defined as <6 months from exposure), the patient might not have seroconverted; this can caste suspicion on the PCR test results, I believe.

In conclusion, the initial six months of infection can be difficult to diagnose with accuracy. If more than six months have passed since exposure, the PCR test results should be very specific for active infection.

Perhaps others will add their thoughts to this as well.

All the best of luck to you, and feel free to read and contribute to our discussion group.

Bill

[JennyPenny2009]

Unfortunately HCV/RNA may be positive before the antibodies show up in the blood in people with early acute infections. This may also happen in those who are immunocompromised. Best thing is to repeat the PCR test in a couple of months.

[mindoza]

Thank you Bill and Mike, for the answers and the resources. It's good there's a community for people struggling or have struggled, or will be struggling, with HCV. Knowing one isn't alone in the struggle gives one some kind of strength.

I'm keeping my fingers crossed (I'm not ready for those expensive and difficult treatments :c ) that I'm not infected, and that I will be waiting for more answers.

Best of luck to all of you, too! :)

[mindoza]

Thanks JennyPenny. Will do that definitely. :)

[mikesimon]

I question your assertion that PCR is not reliable within 6 months. My understanding is that it is reliable in a couple of weeks after exposure. I think 3 weeks form exposure is the time frame I have seen with regard to PCR. If 6 months was right no one would ever be definitively diagnosed in the acute phase and we know that's not the case. My understanding is that a PCR will show hepatitis c much earlier than an antibody test.

Mike

[copyman]

with the result being that low the most likely scenario is that it was a false positive. best of luck

[Bill1954]

Thanks Mike. I thought that NAT testing wasn’t always reliable during the acute phase, and I can see where my choice of wording might have been poorly chosen. Do you know if seroconversion universally occurs at 3 weeks? Because until then, PCR might not detect RNA virus, correct? Hmm…

Bill

[JennyPenny2009]

I think we may be getting stuck here on semantics. The PCR being positive makes it pretty likely that you are infected. The only time I have heard of people being PCR positive but not having the virus is when the serum sample was contaminated and that does not happen very often. Mike is correct that PCR is quite reliable just a few weeks after exposure. It is used to confirm active infection.

[copyman]

I think the fact that mindoza is from Egypt may make it very likely a false positive. The standards in other countries are much different then here in the USA.  He even admits to testing at several different locations so he must not feel comfortable with the tests in his country. I still think he is negative from what he describes. It would be different if he knew that the person the syringe was used on was HCV positive. So without that info the chance he has HCV are remote at best.

[willing]

the following CDC guidelines on HCV testing reporting may be be helpful
http://www.cdc.gov/mmwr/PDF/rr/rr5203.pdf
note in particular the testing flow chart and accompanying discussion (also here:
http://www.cdc.gov/hepatitis/HCV/PDFs/hcv_flow.pdf

Unfortunately, stressful as this may be, there is no immediate answer:

- antibodies take a while to develop. At only 4 weeks after exposure, any Ab test may not be that informative. The above report does reference one case  where Abs did not become detectable for 33 months, though that's extreme. The CDC guidelines suggest detectable Abs at 6 months in 97% of infections.

- even 3rd gen EIAs can have high false positive rates: "the proportion of false-positive results with HCV EIA 2.0 or HCV Version 3.0 ELISA averages approximately 35%". Thus given a positive s/co on an EIA following up with RIBA or NAT/PCR is advised.

- viral RNA is detectable much earlier than host Abs, within a few weeks: "false-negative anti-HCV test results can occur during the first weeks after infection (i.e., before antibody is detectable or during seroconversion), although HCV RNA can be detected as early as 1–2 weeks after exposure to the virus" However, during the early stages of (acute) infection HCV RNA level can fluctuate wildly. Thus the recommendation is to follow up a negative NAT with a RIBA.

In summary, if exposure was that recent, the results of the EIAs are not likely to be definitive. Testing again in a few  months seems advisable. The positive PCR result is not promising. Hopefully, it was an error. Best of  luck.