Tackling the Challenges Associated With Treating Hepatitis C Infection in Pediatric Patients

Hepatitis C virus (HCV) infection is increasingly observed in younger patients. Maternal transmission is currently the main route of HCV acquisition in children, with 1 meta-analysis reporting a transmission rate of 5.8%.¹ Each year in the United States, an estimated 29,000 HCV-infected women give birth to approximately 1700 infected infants.²

“Unfortunately, most likely those numbers will continue to understate the burden of maternal and perinatal HCV as long as screening for pregnant women remains risk-based and mechanisms to improve reporting remain unchanged,” wrote the authors of a review.³

“Universal screening for pregnant women is the first step to improving HCV perinatal surveillance and moving toward HCV elimination because risk-based screening is ineffective in identifying all exposed infants.”³

Other key points are summarized here:

• Rates of follow-up with HCV-infected mothers and their HCV-infected children are low.³
• Ribavirin-based HCV therapies are contraindicated in pregnancy, and safety data are lacking regarding the use of direct-acting antivirals in pregnancy, although such a trial is currently underway.⁴
• From 2006 to 2012, there was a 37% increase in hospitalizations of HCV-infected children, mostly among adolescents and young adults.⁵
• Prevalence in these age groups is likely underestimated as a result of the current risk-based screening practices. One analysis found that 1-time screening of adolescents and young adults is highly cost-effective, especially when it is counselor-initiated and rapid testing is used.⁶
• Without adequate treatment of HCV-infected youth, they “represent a reservoir for continued spread of infection and, among women of childbearing age, a risk of vertical transmission,” the review authors stated.³ “What is required [for eradication] is wider application of antiviral treatment to all infected patients.”
• At present, there is only 1 regimen (sofosbuvir/ledipasvir and sofosbuvir/ribavirin) approved by the US Food and Drug Administration for the treatment of HCV-infected children as young as 12 years. A study is underway to investigate the use of adult-approved pangenotypic regimens in children (ClinicalTrials.gov identifiers: NCT03067129; NCT03022981).

“We are living a historical moment in the management of hepatitis C,” said Claudia Espinosa, MD, MSc, associate professor of pediatrics in the Division of Pediatric Infectious Diseases at the University of Louisville School of Medicine, Kentucky. “This was once a chronic and deadly disease, but new antiretroviral therapies are changing those outcomes. We need to identify infected children and young adults and cure them to eliminate hepatitis C from the United States.”

Infectious Disease Advisor spoke further with Dr Espinosa to learn more about challenges and potential solutions regarding HCV infection in younger patients.

Infectious Disease Advisor: What are some of the challenges pertaining to HCV management in pediatric patients?

Children infected with hepatitis C face environmental, provider, and system-based challenges, such as underreporting. The lack of screening in pregnant women in many states makes it difficult to identify infected children, as the disease may not be symptomatic for years. In fact, Kentucky just recently passed a bill for universal screening. There is a lack of structured protocols to follow-up on those affected children so we can identify earlier, rather than later, those who will require therapy.

There is also a lack of provider education regarding proper follow-up and necessary testing. Some providers may be uncertain about identifying the correct test to use in the setting of many different options.

Inherent to the drug abuse population, there may be a perceived minimal risk for infection to the baby and caregiver changes, and patients may be lost to follow-up.

There are a limited number of specialists treating this condition, and traveling to metro areas may not be affordable for some families with children affected. There are few therapeutic options, as antiviral clinical trials are just ongoing, and only 1 direct-acting antiviral is approved for use in children 12 years and older.

Infectious Disease Advisor: Do you face any difficulties relating to obtaining HCV treatment for your patients?

Insurance companies often use the same regulations for approval of therapy as they do for adults. For example, last year, to obtain approval for the medication in 1 of our patients who acquired the infection perinatally, we had to submit a urine drug screen and repeat testing at 6 months, when this patient has had the infection for her 12 years and has never used drugs. In addition, we were required to submit a serologic testing documenting the fibrosis stage, but this test is not available for children younger than 16 years because it cannot be calculated.

In this aspect, Kentucky has made huge improvements, as Medicaid has eliminated restrictions for therapy this year. However, additional resources should be given so those interventions can be sustained over time.

There is also limited access and availability of drug abuse programs for those teenagers who acquired the disease through intravenous drug use.

Infectious Disease Advisor: How might these issues be approached in clinical practice in terms of screening, treatment, and more?

There is a need for increased resources and infrastructure in clinics that evaluate these children, or a navigator or coordinator seems to be a good alternative. Protocols should be created for individual practices to manage those exposed children and identify the infected ones. Follow-up of exposed babies can be offered by their primary care provider, and infected cases can be referred to more specialized care. Clinicians should report all infections to your health department so we will have better estimates.

Screening for pregnant women should be universal, and reflex testing to HCV RNA polymerase chain reaction should also be performed in all positive cases. Screening for young adults should be universal (this strategy has been cost-effective if the prevalence of the disease is at least 0.59%, but estimates should account for current underreporting).

Treatment should be universal; for example, insurance regulations for authorization of the medications should disappear, and there should be more therapeutic options for infected children. Drug use programs for teenagers and young adults should be enhanced, and access and availability to mental health programs should be improved.

Education to providers, especially those who practice in remote areas where disease is more prevalent, is needed, as are increased resources and infrastructure for those pregnant women who have drug abuse problems.

Infectious Disease Advisor: What are some other notable points for clinicians regarding this topic?

Hepatitis C epidemiology has changed: it is no longer a disease of baby boomers. The disease is more prevalent than we think. We just have to screen more, as many patients do not have identified risk factors. However, screening will not be cost effective unless patients are linked to care.

There is a cure now for hepatitis C, and we need to learn how to use it. Until we treat young adults, we will not see a decrease in prevalence. We need to advocate for our patients and try to obtain therapy for all. Diversification of antivirals in the market means reduction of individual prices of the medication.

Infectious Disease Advisor: What should be next steps in this area in terms of research or otherwise?

Topics that warrant further attention in this area include:

• Testing of different models of linkage to care and follow-up to identify the most effective ones
• Registries at the state level that help to keep track of affected individuals, as well as treatments and outcomes
•  Application of different models of education for providers
• Use of other technologies, such as telemedicine, to support primary care providers in remote and rural areas
• Additional clinical trials that lead to approval of other antivirals for children should continue

References

1. Benova L, Mohamoud YA, Calvert C, et al. Vertical transmission of hepatitis C virus: systematic review and metaanalysis. Clin Infect Dis. 2014;59(6):765-773.

2. Ly KN, Jiles RB, Teshale EH, et al. 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.

3. Espinosa C, Jhaveri R, Barritt AS. Unique challenges of hepatitis C in infants, children, and adolescents. Clin Ther. 2018;40(8):1299-1307.

4. Barritt 4th AS, Lee B, Runge T, et al. Increasing prevalence of hepatitis C among hospitalized children is associated with an increase in substance abuse. J Pediatr. 2018; 192:159-164.

5. Assoumou SA, Tasillo A, Leff JA, et al. Cost-effectiveness of one-time hepatitis C screening strategies among adolescents and young adults in primary care settings. Clin Infect Dis. 2018; 66(3):376-384.