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Saudi Journal of Kidney Diseases and Transplantation
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LETTER TO THE EDITOR Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 5  |  Page : 817-819
Notes on HCV- ELISA Test Results of the Hemodialysis patients


King Fahd Specialist Hospital, P.O. Box 15215, Dammam 31444, Saudi Arabia

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How to cite this article:
Abutaleb N. Notes on HCV- ELISA Test Results of the Hemodialysis patients. Saudi J Kidney Dis Transpl 2008;19:817-9

How to cite this URL:
Abutaleb N. Notes on HCV- ELISA Test Results of the Hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Jul 19];19:817-9. Available from: http://www.sjkdt.org/text.asp?2008/19/5/817/42469
To the Editor,

I noticed that many nephrology colleagues tend to accept reported HCV-ELISA test results without ordering additional confirma­tory tests. Although it is often appropriate and practical, we should be aware of the ELISA test limitations. These limitations have persis­ted, though to a lesser degree, despite the advent of ELISA 3.0 test with its improved sensitivity and specificity rates; this is partly because of factors related to the tested popu­lation itself. In these notes, I would like to summarize some of these limitations and high­light some of the related suggestions.


   A. The problem of high false negative results rate Top


To evaluate this problem accurately, I would like to remind that NAT (e.g.: PCR) testing is being adopted in many countries to test poten­tial blood donors. It is estimated that current HCV-ELISA testing of blood units in addition to ALT would miss only one unit per 230 to 270 thousand tested units. [1] HCV-NAT testing is being carried out on all blood units because of this false negative rate of less than 0.000005. Adolfo Eiras et al reported the iden­tification of three HCV-RNA-positive anti­HCV-negative out of 1,015,482 screened do­nations. [2] NAT screening would bring above false negative rate further down to once in every 2 million blood units. Carrying out this HCV-NAT screening using mini-pools of 25 to 30 blood units is estimated to cost $4.3 million per quality-adjusted year of life [1] or one million $ per each HCV infection prevented. As the rate of false HCV-ELISA negative results is many times higher among the hemodialysis patients, such NAT testing should be more jus­tified for the dialysis patients. Several reasons may explain this finding of higher false nega­tive results among the hemodialysis patients. Hemodialysis patients are relatively immuno­compromised and so have a lower and later antibody response to the acute HCV infection. The window period prior to seroconversion is longer and at times is even permanent! In addition, ALT and other liver enzymes have a lower normal range among dialysis patients. This often results in overlooking the increase in ALT results even within the normal range. In addition, inherit ELISA test false negative rate is still significant even after adopting ELISA 3.0. If a specificity rate of 98.0% * is accepted for ELISA 3.0, the false negative rate would be 2% in a unit with 50% HCV pre­valence just because of the test related accu­racy, a rate that is several tens of thousands times similar rate among blood donors.

HCV-NAT testing among dialysis patients may be suggested in the following instances:

  1. An otherwise unexplained abnormal ALT values: KDIGO draft has suggested consi­dering HCV-NAT testing on facing an abnormal LFT with no obvious explana­tion; including negative testing for HCV and HBV markers. It is the general expe­rience of the nephrologists that most of such cases of otherwise unexplained ab­normal ALT values are secondary to HCV infections. In fact, even when both ELISA and serum PCR HCV tests are negative, occult HCV is still very probable. Barril G. et al. have reported positive PCR HCV test (carried out on blood mononuclear cells) in 24 (60%) out of 40 hemodialysis patients with high ALT (> 28 IU/L) and negative anti-HCV, serum HCV-RNA and HBsAg. [3] The negative ELISA result as discussed above is secondary to delayed seroconversion (acute HCV infection), ab­sent antibody response or lab errors. NAT testing, despite its problems, would detect most of these occult HCV infections.
  2. Occurrence of new HCV infection within the dialysis unit: KDIGO draft suggests that all the patients, in such dialysis unit, be tested with PCR analysis upon facing a new HCV infection that seems acquired nosocomially within the unit. This may help in detecting additional HCV noso­comial infections early on and detecting falsely -ve HCV patients who could be the source of infection.


In addition, I suggest PCR HCV testing in the following two more instances:

  • HD patients returning to their units after receiving HD sessions in units with low standard of infection control care or with a high HCV prevalence.
  • Routine periodic testing along with ELISA (i.e. 3–6 monthly). I suggest performing a single NAT test on a minipool blood sample made out from samples from all the HCV negative patients. The sensitivity of NAT is unlikely to be affected by such dilutions especially on utilizing present blood donor kits. At any time such minipool-NAT tes­ting is reported positive, it would suggest the presence of false negative HCV infected patient(s) among the tested group. If the simultaneously carried out ELISA test is also negative, then NAT test needs to be repeated individually on the entire mini-pool group. By this approach, the false negative results can almost be eliminated at a lower cost.


Colleagues should also be aware about the relatively high false negative PCR results. In addition to the well documented phenomenon of fluctuating HCV viremia, lab errors in con­ducting PCR are apparently not infrequent. HL Zaaijer et al reported that only 5% of 31 Labo­ratories tested for the performance of HCV PCR with known blood samples reported com­pletely correct results! [4]


   B. The problem of high false positive results rate Top


The need to consider supplemental testing to the +ve ELISA test results is especially im­portant in units with relatively low prevalence. In the 2003 guidelines of the Centers for Disease Control and Prevention (CDC) for laboratory testing and result reporting of anti­body to hepatitis C virus, the rate of false +ve HCV results among US dialysis patients was reported at 15% (HCV prevalence about 10%). As HCV prevalence in the Kingdom of Saudi Arabia has halved (70 to 35% ) over the period 1997 to 2006, [5] it is likely that HCV prevalence of 10–20% would be observed in many Saudi dialysis units in the coming years. The impact of such misdiagnosis on the individual patients can not be overemphasized. Predisposition to true HCV infection and unnecessary diagnostic and therapeutic actions are the least conse­quences for accepting such false positive results. RIBA 3.0 or the alternative INNO-LIA HCV Score test should be considered to confirm the ELISA 3.0 positive results. European Guidelines have in fact suggested such confirmation of ELISA results by RIBA testing; which, I believe, should be adopted in our practice.

 
   References Top

1.Stramer SL, Glynn SA, Kleinman SH, et al. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing. N Engl J Med 2004;351(8):760-8.  Back to cited text no. 1    
2.Eiras A, Sauleda S, Planelles D, et al. HCV screening in blood donations using RT-PCR in mini-pool: The experience in Spain after routine use for 2 years, Transfusion 2003;43(6):713-20.  Back to cited text no. 2    
3.Barril G, Castillo I, Arenas D, et al. Intermittent and short daily hemodialysis increase HGF plasma levels and diminish HCV viral load. Hemodial Int 2005;9(1):83.  Back to cited text no. 3    
4.Zaaijer HL, Cuypers HT, Reesink HW, Winkel IN, Gerken G, Lelie PN. Reliability of polymerase chain reaction for detection of hepatitis C virus. Lancet 1993;341(8847):722­4.  Back to cited text no. 4    
5.Saudi J Kidney Dis Transpl 1997, 2006.  Back to cited text no. 5    

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Correspondence Address:
Nasrulla Abutaleb
King Fahd Specialist Hospital, P.O. Box 15215, Dammam 31444
Saudi Arabia
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PMID: 18711305

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