Background: Many children born to HCV-infected mothers in the U.S. never receive recommended anti-HCV antibody (Ab) screening at age ≥ 18 months (mo). Earlier testing by HCV-RNA PCR might facilitate increased screening, though prior studies using older PCR assays reported unacceptably low sensitivity of one-time PCR testing in infants. We hypothesized that testing at age 2-6 mo using modern blood HCV-RNA PCR platforms with enhanced analytical sensitivity and reliability will adequately detect infected infants.
Methods: Medical records of vertically-exposed infants tested for HCV-RNA at age 2-6 mo at Nationwide Childrens Hospital from 1/1/2008 to 12/31/2017 were reviewed. HCV-RNA tests included qualitative (in-house) and quantitative (ARUP reference lab) Cobas Taqman RT-PCR assays (Roche) with lower limits of detection of 1.2-1.9 log10 IU/ml. Diagnostic performance of early PCR screening was determined using a composite gold standard: 1) infected children had ≥ 2 positive PCRs or persistently positive Ab after age 24 mo; 2) uninfected children lacked these criteria and required documentation of a negative Ab at a point after age 18 mo.
Results: During the study period, 639 vertically-exposed infants underwent HCV-RNA testing at age 2-6 mo. Of these, 24 (3.8%) tested positive, consistent with prior estimates of the vertical transmission rate. Blood HCV-RNA levels were high at screening (median 6.7 log10 IU/ml, range 5.2-7.8 log10 IU/ml), and confirmatory PCR tests were positive in all who had repeat testing (n=22). Among 615 infants with negative PCR screening, 444 had reached age ≥ 18 mo, of whom 144 had undergone Ab testing. Ab tests were negative in 142, while 2 children had low positive Ab results at 18 mo. In both cases, repeat PCR and repeat Ab after age 24 mo were negative, suggesting waning maternal Ab rather than true infection. Using the composite gold standard there were 22 true positive, 0 false positive, 144 true negative, and 0 false negative cases, yielding a sensitivity of 100% (95% CI: 85%-100% [Wilson-Brown]).
Conclusion: These findings demonstrate that modern blood HCV-RNA PCR assays have excellent sensitivity for detecting vertically-infected infants as early as 2-6 months of age and may improve HCV surveillance given the substantial number of children lost to follow-up prior to 18 mo Ab screening.
C. Gowda, None
P. J. Sanchez, None