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To the Editor:

The medical decision article by Lai et al [1] demonstrating the cost-effectiveness of nucleic acid-amplification testing (NAT) for hepatitis C virus (HCV) bears further scrutiny. The issue at hand is the residual window period infection after serology testing in the general donor population. Although it is difficult to decipher, it appears the authors have used prevalent infection rather than the more appropriate incident infection rate in their analysis. Since these two numbers are >100-fold different the cost–benefit is considerably inaccurate.

Potential deceased donors are screened by history, physical examination and laboratory testing. History is often from collaborative sources. Laboratory evaluation includes screening for viral infections with serology. As stated by the authors in their methods, they assume that all patients with prevalent infection determined by positive serology are excluded from donation. The remaining sero-negative subjects are potential donors. However, a small proportion of these will be infectious but missed by serology if the patient has been screened after they contracted a new infection but before they sero-convert. The time from infection to sero-conversion is known as the window period. The probability of missing a covert sero-negative infection is a function of the size of the window period (10 weeks for HCV) and the incidence rate (not prevalence) of a new infection in a susceptible naïve host. Although higher prevalence is associated with higher incidence rates, they are not the same and can be different by several orders of magnitude particularly if the infection persists and has a low mortality rate. For example in a study estimating the risk of HCV in tissue donors, men age 30–49 had a prevalence of confirmed HCV of 3.3%, yet the incidence rate of new infections was estimated to be only 15.67 per 100 000 patient years (0.01567%) [2]. It is not clear in the paper by Lai et al [1] what incidence rates were used since none were reported.

I suspect the incidence rate used by Lai et al [1] was 3.5% per year for HCV; however, this is the prevalence in the population. Assuming three organ recipients from one donor, 2.34 lost quality adjusted life years (QALY) per infected recipient, and a window period infection that is reduced from 10 weeks to 0, the estimated increase in QALYs with NAT would be in the range of 0.0473 QALYs. For an incremental screening cost of $150, the incremental cost utility would be $3174/QALY, which is very close to Lai et al's [1] value of $3290.

The more likely risk of transmission of HCV from the general donor population screened by serology testing is 1/42 000 [2, 3]. Lai et al's [1] rough estimate is probably 1/150. These are very different. Using the lower risk value catapults the incremental cost utility estimate to >$500 000/QALY assuming the test costs $150. I admit these calculations do not include the costs averted from transmitted infection, the lost benefit of false positive NAT tested organs that are not used and the residual infection even with NAT.

It is important to point out that the residual risks for HCV used by Lai et al [1] are very appropriate in higher risk donors such as intravenous drug users [3]. In these circumstances, the cost/QALY gained with NAT for HCV would be very attractive and highly recommended [3].

It should be pointed out that the estimated costs per QALY for HCV NAT exceed $1 million for blood [4]. The observed transmission of HCV to transplant recipients currently is far less that the 1/150 estimated by Lai et al [1] even with considerable underreporting [5]. Together with the above analysis, there is a reason to believe that the findings by the authors are inaccurate, will mislead policy makers and must be re-evaluated with specific attention and explicit details of the incident infection rates for HCV used in their model.

  • B. Kiberd*

  • Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada

  • *Corresponding author: Bryce Kiberd, bryce.kiberd@dal.ca

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The author of this manuscript has no conflicts of interest to disclose as described by the American Journal of Transplantation.

References

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