Catherine A. Chappell, MD, MSc
Debra L. Bogen, MD, FAAP, FABM

One of the most significant consequences of the opioid crisis is the increasing prevalence of hepatitis c virus (HCV) infection among young persons, including pregnant women. In 2015, the Centers for Disease Control (CDC) reported a 364% increase in HCV infection among persons less than 30 years of age.1 Now in Pennsylvania, young persons outnumber the “Baby Boomers” (persons born between 1945 to 1965) with HCV infection.2 Currently, recommendations are to universally screen all Baby Boomers for HCV.3 However, there are conflicting guidelines regarding HCV screening during pregnancy. While the Infectious Disease Society of America (IDSA) recommends universal antenatal HCV screening, the American College of Obstetrics and Gynecology (ACOG) recommends risk-based screening. In our community, we are not currently performing universal antenatal HCV screening.

The rising burden of HCV among women of childbearing age makes the concern for perinatal transmission of HCV more pressing. The risk of transmission of maternal HCV infection to an exposed infant is 5.8%.4 Although there are now curative treatments (ledipasvir/sofosbuvir, velpatasvir/sofosbuvir and glecaprevir/pibrentasvir) for HCV for adults and increasingly available treatment for children, there are no interventions available to prevent the transmission of HCV during pregnancy. However, a study of the safety and efficacy of ledipasvir/sofosbuvir during the second trimester is currently underway at UPMC Magee-Womens Hospital (ClinicalTrials.gov Identifier: NCT0268300). Among infants with perinatally acquired HCV, almost half spontaneously clear the infection and the other half remain infected, but only a minority progress to cirrhosis during childhood.5 However, those with perinatally acquired HCV develop cirrhosis at younger ages and at higher rates than individuals who acquire HCV later in life.6 

Because of the risk of perinatal transmission, it is critically important to know women’s HCV status to both arrange monitoring and treatment for women and to know which infants should have HCV screening. Unfortunately, the complexity of risk-based screening makes it hard to implement. In a recent study that evaluated risk-based screening in pregnancy, only one-third of pregnant women with risk factors were screened for HCV.7 Even when implemented adequately, risk-based screening fails to identify many patients with HCV. In a recent study from Kentucky, rates of screening increased from 17.9% using risk-based screening, to 100% using universal screening. While the rate of positive HCV antibodies did not increase significantly, (4.3% risk-factor based versus 4.9% universal), the rate of confirmatory HCV RNA markedly increased (54.3% to 100%). Ultimately, almost 10 times as many women with positive HCV RNA were identified (31 women during risk-based screening, 306 during universal screening).8 It is unlikely that temporal increases in local incidence alone could account for this difference, which is much more easily explained by improvements in the total number of women receiving proper testing. Furthermore, recent cost-effectiveness studies found that universal screening for HCV during pregnancy is more cost effective even if the prevalence is 0.07%, which is the estimated prevalence in Hawaii (the state with the lowest HCV prevalence).9,10  Importantly, without universal HCV screening during pregnancy, cases of HCV in children will be missed. Pregnant women in Allegheny County are routinely screened for hepatitis B, HIV and syphilis, despite the significantly lower rate of these infections. It is time to move to universal HCV screening during pregnancy. 

Even if the HCV status is known for every pregnant woman, there are still challenges when screening for HCV in children who are perinatally exposed. Sadly, most infants who are perinatally exposed are not screened for HCV.11-13 Current routine screening practices focus on detection of anti-HCV antibodies. Due to passage of these antibodies from mother to baby through the placenta, screening for anti-HCV antibodies before 15-18 months of age is not an accurate indication of infection. It is challenging for pediatric primary care providers to ensure that that at-risk children are screened on or after 18 months of age, because there is no other routine laboratory testing at this age, and documentation in the electronic medical record for risk of perinatal HCV infection is inconsistent. Each individual physician has to develop their own reminder system, which can be overlooked if the child sees another provider. HIPAA violations also are possible when documentation in the child’s chart references the mother’s medical history (“exposure to hepatitis C in utero” or “at risk for HCV infection”). The UPMC pediatric practices implemented an Epic Best Practice Alert that reminds providers to screen for HCV on or after 17 months of age for those with perinatal exposure by temporarily linking this information from the mother’s chart to the infant’s, with maternal permission. Utilizing the electronic health system is critical to avoid missing cases of perinatal HCV transmission. 

In 2012, HCV surpassed all other reportable infectious diseases in causing deaths in the United States.14 We now have highly effective, easily administered medications. However, we continue to miss opportunities to diagnose and treat the increasing number of individuals living with HCV, and we are falling short especially when it comes to pregnant women and children.   Pregnancy is a window of opportunity to screen for HCV. Every pregnant woman should know whether she has HCV so that she can be linked to treatment if needed for herself and screening decisions for her baby. Every infant exposed to HCV should be screened for perinatal HCV infection, and the electronic health system should be utilized so no infants are missed.  Anything less is a disservice to the families living in our community. 

 

References

  1. Zibbell, J.E., et al., Increases in hepatitis C virus infection related to injection drug use among persons aged </=30 years – Kentucky, Tennessee, Virginia, and West Virginia, 2006-2012.MMWR Morb Mortal Wkly Rep, 2015. 64(17): p. 453-8.
  2. Morse, A., A.S.t. Barritt, and R. Jhaveri, Individual State Hepatitis C Data Supports Expanding Screening Beyond Baby Boomers to All Adults. Gastroenterology, 2018. 154(6): p. 1850-1851 e2.
  3. Smith, B.D., et al., Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep, 2012. 61(RR-4): p. 1-32.
  4. Benova, L., et al., Vertical transmission of hepatitis C virus: systematic review and meta-analysis. Clin Infect Dis, 2014. 59(6): p. 765-73.
  5. Espinosa, C.M. and R. Jhaveri, Update on the management of hepatitis B and C infections in the neonatal period. Semin Perinatol, 2018. 42(3): p. 185-190.
  6. Modin, L., et al., Epidemiology and natural history of hepatitis C virus infection among children and young people. J Hepatol, 2019. 70(3): p. 371-378.
  7. Boudova, S., K. Mark, and S.S. El-Kamary, Risk-Based Hepatitis C Screening in Pregnancy Is Less Reliable Than Universal Screening: A Retrospective Chart Review. Open Forum Infect Dis, 2018. 5(3): p. ofy043.
  8. Rose M, Myers J, Evans J, Prince A, Espinosa C, editors. Abstract 87: Hepatitis C risk-based vs. universal screening among pregnant women: implementation and cost-effectiveness analysis. The Liver Meeting; 2018 November 11; San Francisco, CA.
  9. Chaillon, A., et al., Cost-Effectiveness of Universal Hepatitis C Virus Screening of Pregnant Women in The United States. Clin Infect Dis, 2019.
  10. Tasillo, A., et al., Short-Term Effects and Long-Term Cost-Effectiveness of Universal Hepatitis C Testing in Prenatal Care. Obstet Gynecol, 2019. 133(2): p. 289-300.
  11. Kuncio, D.E., et al., Failure to Test and Identify Perinatally Infected Children Born to Hepatitis C Virus-Infected Women. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2016. 62(8): p. 980-5.
  12. Delgado-Borrego, A., et al., Expected and actual case ascertainment and treatment rates for children infected with hepatitis C in Florida and the United States: epidemiologic evidence from statewide and nationwide surveys. The Journal of pediatrics, 2012. 161(5): p. 915-21.
  13. Chappell, C.A., et al., Hepatitis C Virus Screening Among Children Exposed During Pregnancy.Pediatrics, 2018. 141(6).
  14. U.S. Department of Health and Human Services. National Viral Hepatitis Action Plan 2017-2020. https://www.hhs.gov/sites/default/files/National%20Viral%20Hepatitis%20Action%20Plan%202017-2020.pdf. Accessed May 10, 2020.