Some states have reported a disproportionate increase in HCV infection in reproductive-age women, heightening concern about mother-to-child transmission.8 Dr Kourtis said that this has led some states to require HCV screening for all pregnant women, an approach many medical societies now recommend. “Part of the reason universal testing during pregnancy is not currently recommended [by the CDC] is that there is nothing that can be done to prevent transmission to the infant if the pregnant woman is found to [have] HCV infect[ion],” she noted.

Because anti-HCV antibody testing in children younger than 18 months will detect maternal antibodies, the CDC and American Academy of Pediatrics currently recommend using HCV RNA measured by polymerase chain reaction to screen infants born to mothers with HCV infection.8 However, testing should be delayed until after 1 month of age.8

Dr Kourtis stated that pediatric HCV infection is typically asymptomatic in the early years and progresses slowly. “Keep in mind that 1 in 5 children who get HCV infection will clear it on their own within the first couple of years of the infection. [In] the rest, a chronic infection [will develop] that will progress later in life…and severe disease will not occur until 20 to 30 years later,” she said. This is supported by the results from a study on the long-term effects of childhood-acquired HCV infection, which found that cirrhosis typically developed a median of 33 years after diagnosis.1 Nevertheless, liver disease is possible during childhood and is typically more severe in children with comorbidities such as HIV.5

Role of DAAs in Prevention and Management

To date, no strategies are available to prevent vertical transmission of HCV, which requires complete suppression of viremia (detectable virus in the blood).8 “If a pregnant woman was to be cured of her HCV infection, any risk of transmission to the baby would be eliminated,” Dr Kourtis said. However, ribavirin-based regimens are contraindicated during pregnancy because of ribavirin’s teratogenic nature.8 Although studies have shown that newer DAAs can cure HCV, Dr Kourtis said trials have not established whether they are safe to use during pregnancy and most clinicians would not administer them to women who are pregnant or attempting to conceive. She noted clinical trials are underway or being planned that will evaluate the safety of DAAs during pregnancy. For example, an ongoing phase 1 trial (NCT02683005) is assessing the safety and pharmacokinetics of sofosbuvir plus ledipasvir in 15 women with chronic HCV infection who are in their second or third trimester of pregnancy.9

“Based on the preclinical information we have available for DAAs, I am optimistic that they will be safe for use during pregnancy and, if indeed they are proven safe, I expect that we will be able to use them in pregnant patients and that they will achieve high cure rates with rapid suppression of HCV viremia,” Dr Kourtis said. “The fact that they require a short duration of 8 weeks means that treatment can be achieved late in pregnancy or prior to delivery,” she said.

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Dr Kourtis said there are no treatments approved by the US Food and Drug Administration to treat HCV infection in children younger than 3 years of age but that ongoing clinical trials are evaluating DAAs approved for adult use in children 3 years and older. “We expect that soon there will be DAAs approved for children age 6 years and older — and perhaps even younger,” she said. Ongoing phase 2 trials are evaluating sofosbuvir plus velpatasvir (NCT03022981)10 and sofosbuvir plus daclatasvir (NCT03487848)11 in children aged 3 to 17 years with chronic HCV infection, and a phase 2 trial evaluating sofosbuvir plus ledipasvir in a similar population recently finished but has yet to publish results (NCT02249182).12 The US Food and Drug Administration recently approved sofosbuvir with either ledipasvir or ribavirin to treat chronic HCV in children 12 years and older, based on clinical trial data showing both regimens achieved a sustained virologic response greater than 95% after 12 weeks of treatment.8

Conclusions

Establishing the safety of DAA use during pregnancy and broadening HCV screening to include all pregnant women offer the best chance at preventing perinatal HCV infection. “We have the precedent of HIV infection, where the risk of vertical transmission is much higher and where that risk has been almost eliminated with use of antiretroviral drugs during pregnancy,” Dr Kourtis said. “I am optimistic that in the not-so-distant future, we will achieve the same for HCV,” she concluded.

References

  1. Modin L, Arshad A, Wilkes B, et al. Epidemiology and natural history of hepatitis C virus infection among children and young people [published online November 27, 2018]. J Hepatol. doi: 10.1016/j.jhep.2018.11.013
  2. Rodrigue JR, Balistreri W, Haber B, et al. Impact of hepatitis C virus infection on children and their caregivers: quality of life, cognitive, and emotional outcomes. J Pediatr Gastroenterol Nutr. 2009;48(3):341-347.
  3. Nydegger A, Srivastava A, Wake M, Smith AL, Hardikar W. Health-related quality of life in children with hepatitis C acquired in the first year of life. J Gastroenterol Hepatol. 2008;23(2):226-230.
  4. El-Shabrawi MH, Kamal NH. Burden of pediatric hepatitis C. World J Gastroenterol. 2013;19(44):7880-7888.
  5. Nwaohiri A, Schillie S, Bulterys M, Kourtis AP. Hepatitis C virus infection in children: how do we prevent it and how do we treat it? Expert Rev Anti Infect Ther. 2018;16(9):689-694.
  6. Benova L, Mohamoud YA, Calvert C, Abu-Raddad LJ. Vertical transmission of hepatitis C virus: systematic review and meta-analysis. Clin Infect Dis. 2014;59(6):765-773.
  7. Ly KN, Jiles RB, Teshale EH, Foster MA, Pesano RL, Holmberg SD. Hepatitis C virus infection among reproductive-aged women and children in the United States, 2006 to 2014. Ann Intern Med. 2017;166(11):775-782.
  8. Espinosa C, Jhaveri R, Barritt AS IV. Unique challenges of hepatitis C in infants, children, and adolescents. Clin Ther. 2018;40(8):1299-1307.
  9. ClinicalTrials.gov. Study of hepatitis C treatment during pregnancy (HIP). https://clinicaltrials.gov/ct2/show/NCT02683005. Updated December 6, 2018. Accessed December 30, 2018.
  10. ClinicalTrials.gov. Sofosbuvir/velpatasvir in adolescents and children with chronic HCV infection. https://clinicaltrials.gov/ct2/show/NCT03022981. Updated January 9, 2019. Accessed January 22, 2019.
  11. ClinicalTrials.gov. Evaluation of daclatasvir (DCV) in combination with sofosbuvir (SOF) in children with chronic hepatitis C (CHC) infection. https://clinicaltrials.gov/ct2/show/NCT03487848. Updated November 27, 2018. Accessed January 2, 2019.
  12. ClinicalTrials.gov. Safety and efficacy of ledipasvir/sofosbuvir fixed dose combination +/- ribavirin in adolescents and children with chronic HCV-infection. https://clinicaltrials.gov/ct2/show/NCT02249182. Updated October 23, 2018. Accessed January 2, 2019.