Earlier Testing of Infants With Perinatal Hepatitis C Exposure: A Key Step Toward Elimination

Hepatitis C virus (HCV) infection continues to be a major national public health problem and is targeted for domestic and global elimination. Driven by the ongoing opioid epidemic, HCV incidence has been rising in the United States over the past decade, with highest infection rates among young adults including women of childbearing age.¹  This is significant because if these young adults with HCV viremia get pregnant, their infants are perinatally exposed to the virus. In 2020, as part of a strategy to increase testing of all adults, the Centers for Disease Control and Prevention (CDC) recommended universal HCV antibody screening with every pregnancy, a critical first step to improve maternal health and enhance identification of infants at risk for HCV.²  With a 3% to 8% risk, perinatal transmission is still the most common route of HCV infection among children, and an increasing number of infants have been infected over recent years.³  Most infants with HCV infection are asymptomatic, so the diagnosis depends on subsequent testing of perinatally exposed infants to rule out infection. Historically, it was recommended that all infants with HCV exposure be screened for anti-HCV antibodies at ≥18 months. With this previous recommendation, numerous studies consistently demonstrated that 75% to 90% of exposed infants were never tested or linked to care.^4,5  The reasons for this poor test rate are multifactorial, but a recommendation to wait 18 months in a population who often has many complicated social factors certainly was a major factor.^4,5  Frustrated by these poor rates and the high loss to follow up, many practitioners began sending HCV RNA tests earlier than 18 months. The American Association for the Study of Liver Diseases/Infectious Diseases Society of America HCV guidance panel did finally offer early HCV RNA testing as an option for perinatally exposed infants. The undebatable failure of our current approach to adequately test all HCV perinatally exposed children calls for a new national screening strategy.

In the November 2023 issue of Morbidity and Mortality Weekly Report, the CDC published its “Recommendations for HCV testing among perinatally exposed infants and children.”⁶  Based on a comprehensive literature review, the new recommendations prioritize early testing at 2 to 6 months of age with a single HCV RNA test, with alternative for HCV RNA testing up to 17 months of age for those not tested previously (Fig 1). Coming at a time when most infants are being seen for well visits and immunizations, implementation of the CDC’s new guidance to test all perinatally exposed infants between 2 and 6 months of age will result in increased identification and treatment of children with perinatally acquired HCV infection. Infants with undetectable HCV RNA (the vast majority) do not require any further follow-up unless clinically warranted. Infants with detectable HCV RNA can be linked to a health care provider with expertise in pediatric hepatitis C management (if available) or evaluated with local or telehealth support for eventual treatment after aged 3 years. The rationale for a single test lies in the high sensitivity (100%; 95% confidence interval, 87.5–100) and specificity (100%; 95% confidence interval, 98.3–100) of the current real-time polymerase chain reaction assays and no subsequent discordant results between subsequent antibody testing at 18 months.⁷  A recent study of the new recommendation demonstrated that the accelerated testing strategy at 2 to 6 months is cost-effective (Supplemental Information).^8–24

This revised recommendation is a very important step but is only 1 among many required to achieve comprehensive HCV elimination efforts during pregnancy and early childhood. To successfully identify all exposed infants and prevent loss to follow up and inadequate testing, universal HCV antibody screening during pregnancy must actually be implemented, with any pregnant patient having a positive screen receiving automatic reflex HCV RNA testing. Current data suggest that most prenatal providers still have not engaged in universal HCV screening during pregnancy. Seamless collaboration between obstetricians, newborn care providers, and specialists is required to ensure that, ideally, pregnant patients are treated during pregnancy (once this is recommended, the current recommendation is individualized decision-making) or at worst in the postpartum period, that HCV exposure is documented in the infants’ medical records and communicated to their primary care providers, and that parents/caregivers are counseled about perinatal HCV exposure and the plan for infant testing. Other logistical steps needed to successfully implement the new testing strategy are: health care provider education about when and how to test (eg, placing the correct laboratory order, specimen collection logistics, which laboratory to send sample); shifting to exclusive HCV RNA testing because identifying HCV viremia that requires treatment is the primary goal; evaluation of alternative sample collection (such as heel sticks) that are more easily obtained in pediatric primary care settings; coordination of care for referral to a specialist (if there is no health care provider with expertise in pediatric hepatitis C management) for follow up and retesting at approximately age 3 years when direct acting-antiviral therapy can be administered; and unobstructed access to direct acting-antiviral therapy for all patients regardless of age, which offers the promise of near 100% cure rates.

Although this process may seem daunting to design, the reality is that our health system already has an incredibly successful infrastructure in place that performs all of these steps for perinatal HIV and hepatitis B exposure and screening. These comprehensive programs have been enormously successful in achieving the near elimination of HIV and hepatitis B vertical transmission in the United States. Using the existing perinatal HIV and hepatitis B infrastructure to care for pregnant persons with HCV and their infants after delivery could provide seamless and comprehensive care with testing and treatment of all. This will take an investment of public health resources, but the more modest resources needed to expand existing systems with the promise of HCV elimination certainly seems like a good value.

The revised testing recommendation is not the end of the story. The challenge of increased HCV infections will require efforts to work “upstream” of the perinatal exposure. Can we treat most or all patients during pregnancy when we know they consistently come to appointments and are engaged in their care? Can we design and implement better prevention measures that include safer injection practices and more widespread drug treatment programs that reduce incident HCV infections?

Pediatricians reading this may ask what they need to do next. The call to action will sound very familiar to previous calls. Pediatricians need to familiarize themselves with the relevant facts of HCV vertical transmission, need to know which test to order and when, and need to coordinate with their obstetric colleagues to efficiently and confidentially share the HCV test results obtained during pregnancy to facilitate subsequent infant testing. Pediatricians are used to this role for HIV and hepatitis B, so these steps should feel very familiar.

The elimination of HCV as a public health problem will require us to identify and treat HCV in every subpopulation without exclusion (“elimination means everyone”). With these new recommendations, we move 1 step closer to a comprehensive strategy to test and treat every pregnant patient and every infant exposed so they can personally benefit from a cure of the HCV infection and be spared the risk of chronic liver disease while also being meaningfully included in our national elimination efforts.