A rise in hepatitis C virus (HCV) infection has been observed among reproductive-aged women and their children.1,2 A study assessing data from the National Notifiable Diseases Surveillance System showed that HCV rates doubled among women of reproductive age between 2006 and 2014, from 15,550 cases to >31,000 cases.1 A 3.2-fold higher rate of HCV infection was also observed among children aged 2 to 3 years compared with those aged 12 to 13 years, suggesting mother-to-child transmission.1 This trend was further demonstrated in an analysis of HCV infection during pregnancy, which found a 5-fold increase among pregnant US women between 1998 and 2011, from 42 to >210 HCV cases per 100,000 births.2 Although this trend was observed across all risk groups, it was particularly concerning among already high-risk groups, such as illicit drug users and those engaging in high-risk sexual behaviors (eg, multiple partners).2

The rise in HCV infection during the last 2 decades, including among young women, has been attributed to increasing injection drug use spurred by the onset of the opioid epidemic in the 1990s.3,4 Before this, HCV transmission occurred mainly through blood transfusions and organ transplantations that took place before the introduction of routine blood screening for HCV antibody in the early 1990s; thus, before the early 2000s, HCV infection was mostly observed in older adults.3,5 Today, injection drug use is a major risk factor for HCV infection, with approximately 50% of people who inject drugs having been exposed to HCV and 25% of these individuals being younger than 25 years.3 The Centers for Disease Control and Prevention reported a dramatic parallel increase in HCV infection and opioid injection between 2004 and 2014, with increases greatest among white Americans, women, and young adults (aged ≤39 years).4 In these populations, HCV infection increased by 300% in white Americans, 250% in women, 400% among people aged 18 to 29 years, and 325% in people aged 30 to 39 years, with drug treatment admissions for opioid injection increasing by 134%, 99%, 622%, and 83% in these populations, respectively.4

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As more women of reproductive age are at risk of harboring HCV and transmitting it to their children during pregnancy or delivery, this population represents an important opportunity to meet the World Health Organization goal of significantly reducing HCV-related morbidity and mortality rates by 2030.6 Infectious Disease Advisor had the opportunity to discuss HCV risk mitigation and treatment in women of reproductive age with Tatyana Kushner, MD, MSCE, assistant professor of medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York City. Dr Kushner recently coauthored the article, “Hepatitis C in Pregnancy: A Unique Opportunity to Improve the Hepatitis C Cascade of Care,” which was published in Hepatology Communications.7

What disparities are there in screening women and children for HCV, and how could screening be improved in both groups?

The issue in screening women is that most hospitals still only recommend risk-based screening rather than universal screening for HCV during pregnancy, the latter of which has been recommended by the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) HCV guidelines.8 Thus, women who do not report their risks, or are not asked to provide a thorough risk history, may not be screened, and subsequently, HCV diagnoses are missed. In the pediatric setting, as few as 9% of children of mothers with HCV receive the appropriate follow-up testing.9 This is because there is generally no infrastructure in place to follow children of mothers with HCV and link them to care. Screening can be improved in both groups by advocating for more broad-based, universal screening, as well as putting systems in place so that children of mothers with HCV do not get lost to follow-up.

What are the challenges involved in treating women for HCV infection during their reproductive years?

There are 2 key challenges. The first challenge is to make the diagnosis, as women with risk factors for HCV, such as injection drug use, may not have access to or are unlikely to seek healthcare. The second challenge is to link these women to care because they may not have health insurance or have regular medical follow-up. In certain cases, it may only be possible for them to obtain HCV treatment through substance use disorder programs, and there is currently no emphasis on co-locating care for HCV with substance use disorder treatment programs.

What treatment gaps need to be addressed in treating women with HCV who are of childbearing age?

The major treatment gap is understanding the role of treatment during pregnancy and in the postpartum period. At this time, the AASLD-IDSA HCV guidelines contraindicate direct-acting antiviral (DAA) treatment once women become pregnant, favoring treatment initiation before or after pregnancy because the safety of DAAs remains unknown.8 However, this recommendation may change if larger studies and more mature data regarding DAA use during pregnancy mirror the results observed in a small pilot study assessing ledipasvir/sofosbuvir during pregnancy in women with chronic genotype 1 HCV infection.10 All women receiving ledipasvir/sofosbuvir were cured of HCV, and their neonates appeared healthy and were HCV negative at 6 months of follow-up. However, the study was small, with few patients enrolled, and we will likely need larger studies to provide enough data to shift the recommendation toward treatment during pregnancy.

If DAA is ultimately deemed to be safe during pregnancy, the optimal timing of treatment also needs to be determined. It has been suggested that risk to the fetus could be mitigated by waiting until the third trimester to initiate treatment. Until more data on the safety of treatment during pregnancy and in the postpartum period become available, treatment decision-making should be individualized, and the potential risks and benefits of DAA treatment during pregnancy should be discussed with patients so that they can be informed participants in their care.

Are there any steps that can be taken that can prevent HCV transmission from mother to child, whether in utero or during delivery?

We think that antiviral therapy during pregnancy may decrease the risk for transmission, although the data to support this are limited, as there are no randomized controlled trials assessing the effect of antiviral therapy during pregnancy on HCV transmission to the fetus. Some risk mitigation strategies that can be considered for all pregnant women include limiting invasive monitoring during pregnancy and avoiding prolonged rupture of membranes during delivery. However, based on studies performed to date, there is no evidence that caesarean delivery vs vaginal delivery reduces transmission risk.

Is there any take-home message you would like to share?

One critical message is that pregnancy is an opportune time to screen women for HCV. It is a time when they are engaged and participating in their own healthcare and, subsequently, is a time when we can identify cases of HCV that might otherwise go undiagnosed until later stages. HCV treatment during pregnancy should be investigated, as it may allow us to cure more women with HCV and decrease mother-to-child transmission. Both widespread screening and determination of proper treatment in women of reproductive age are imperative to working toward the World Health Organization goal of eventual HCV elimination.

References

1. 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.

2. Salemi JL, Spooner KK, Mejia de Grubb MC, et al. National trends of hepatitis B and C during pregnancy across sociodemographic, behavioral, and clinical factors, United States, 1998-2011. J Med Virol. 2017;89(6):1025-1032.

3. Shiffman ML. The next wave of hepatitis C virus: the epidemic of intravenous drug use. Liver International. 2018;38(suppl 1):34-39.

4. Increase in hepatitis C infections linked to worsening opioid crisis [news release]. Centers for Disease Control and Prevention website. https://www.cdc.gov/nchhstp/newsroom/2017/hepatitis-c-and-opioid-injection.html. Published December 21, 2017. Accessed November 13, 2019.

5. Hepatitis C questions and answers for the public. Centers for Disease Control and Prevention website. https://www.cdc.gov/hepatitis/hcv/cfaq.htm. Updated September 10, 2019. Accessed November 15, 2019.

6. Global Health Sector Strategies on Viral Hepatitis 2016-2021. World Health Organization website. http://apps.who.int/gb/ebwha/pdf_files/WHA69/A69_32-en.pdf?ua=1. Published April 22, 2016. Accessed November 13, 2019.

7. Kushner T, Terrault NA. Hepatitis C in pregnancy: a unique opportunity to improve the hepatitis C cascade of care. Hepatol Comm. 2019;3(1):20-28.

8. HCV guidance: recommendations for testing, managing, and treating hepatitis C. AASLD-IDSA website. https://www.hcvguidelines.org. Accessed November 14, 2019.

9. Chappell CA, Hillier SL, Crowe D, et al. Hepatitis C virus screening among children exposed during pregnancy. Pediatrics. 2018;141(6):1-8.

10. Chappell CA, Krans E, Bunge K, et al. A phase 1 study of ledipasvir/sofosbuvir in pregnant women with hepatitis C virus. Abstract presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle, WA.