Use of polymerase chain reaction and antibody tests in the diagnosis of vertically transmitted hepatitis C virus infection

Abstract

Data on patterns of polymerase chain reaction (PCR) and antibody test results in infants born to hepatitis C virus (HCV)-infected mothers were systematically reviewed to aid development of optimum testing schedules and diagnostic criteria for vertically exposed infants and to facilitate early identification of infected infants. Survival and cross-sectional analyses were used to estimate the timing of initial PCR positivity and subsequent PCR negativity in infected infants, and maternal antibody loss in uninfected infants was estimated as a weighted average of individual study findings. Of 74 eligible infants with strong evidence of HCV infection, an estimated 89% (90% confidence interval, 80-95%) were first PCR positive by 3 months of age, and less than 10% had subsequent PCR negativity attributable to intermittent viraemia or resolved infection in the first 18 months of life. The negative predictive value of PCR at 3 months of age was greater than 98% at an assumed rate of 5% vertical transmission, but as low as 88% at 25% transmission. The inclusion of 22 infants, each with a single PCR-positive result, increased the estimated frequency of resolved infections but made little difference to other estimates. A minority of PCR-positive infants had periods of antibody negativity by second- or third-generation assays, and among 297 uninfected infants, maternal antibody was not detected beyond 18 months. Thus, the majority of infected infants may be persistently PCR positive from 3 months of age, and the negative predictive value of PCR at 3 months is generally high. However, poor repeatability of PCR, inadequate infant follow-up, and inclusion of postnatally infected infants limits interpretation of the pooled data. Further studies using standardised PCR methodologies are needed.

Mother‐to‐infant transmission of hepatitis C virus: Rate of infection and assessment of viral load and IgM anti‐HCV as risk factors*

“…In the other four infants, transmission occurred probably at the time of birth, and the lack of viral RNA during the first few weeks of life could be ascribed to an inefficient viral replication in the newborn liver and/or to a low-grade exposition. This confirms that the best timing of HCV RNA testing to detect perinatal infection is the 3rd to 4th month of life [Thomas et al, 1997;Conte et al, 2000].…”

Vertical Transmission of Hepatitis C Virus in a Cohort of 2,447 HIV-Seronegative Pregnant Women: A 24-Month Prospective Study

“…Vertical transmission of the virus may take place either in utero (transplacental transfer), perinatally, or, rarely, through breast-feeding (9,12,13). Maternal anti-HCV antibodies (immunoglobulin G) are transferred passively to the fetus and may be present in the infants until 12 to 15 but not beyond 18 months of age (14,15).…”

Active surveillance of hepatitis C infection in the UK and Ireland

“…A total of 29 children (16%), including both those with HCV through MTC transmission and those infected through other routes had two or more consecutive samples negative for HCV RNA by PCR. Wide intraindividual variation in PCR positivity has been previously reported among vertically infected children16 and longer follow up is required to confirm whether these children have really cleared infection. Intermittent viraemia is well recognised in adult HCV infection, and viraemia in pregnant women has been shown to be positively related to the risk of MTC HCV transmission 8…”