Tatyana Kushner, MD, MSCE
Icahn School of Medicine at Mount Sinai
Catherine A. Chappell, MD
University of Pittsburgh
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We read with great interest the Special Article by Jhaveri et al. entitled “Responsible Inclusion of
Pregnant Individuals in Eradicating Hepatitis C virus.”1 This article is timely and draws attention to
pregnant women, a subpopulation that has been ignored in the study of hepatitis C (HCV) treatment.
Pregnancy is an ideal window of opportunity due to the high engagement in healthcare of
reproductive-aged women. The AASLD/ IDSA, USPSTF and CDC now all recommended universal
HCV screening during pregnancy which will lead to increased diagnosis of HCV during pregnancy.
However, the American College of Obstetrics and Gynecology (ACOG) has been hesitant to
recommend universal screening due to the lack of treatment available during pregnancy.2 Jhaveri et
al. identified only one pharmacokinetic study of sofosbuvir/ledipasvir, which demonstrated safety,
tolerability, and effectiveness of direct-acting antiviral (DAA) therapy in nine pregnant women.
Guidance from the AASLD/ IDSA suggests that “women who become pregnant while on DAA
therapy should discuss the risks versus benefits of continuing treatment with their physicians.”3 This
“guidance” puts providers in the difficult position of providing advice with minimal published data on
DAA safety in pregnancy.
We agree with Jhaveri et al. that a clinical trial of HCV treatment during pregnancy ideally should be
sponsored by the NIH, leading a public-private partnership in coordination with the FDA. However,
there is no clear funding mechanism from NIH for larger trials for HCV DAAs and no NIH network of
study sites in high HCV prevalence areas. If the NIH/FDA truly supports ethical research in pregnant
women then they should dedicate funding or require industry to include pregnant women in studies
prior to FDA approval for medications. An alternative approach would be a larger industry sponsored
study which evaluates the use of a pangenotypic DAA regimen during pregnancy. This strategy
would require the pharmaceutical company to have a commitment to the health pregnant women (an
honorable cause), yet could be in opposition to a successful business strategy particularly for
medications that are closer to the patent expiration date. A critical first step would be to compare
DAA treatment compared to the current standard of care (no treatment) on pregnancy and neonatal
outcomes to convince providers that treatment is as safe as no treatment. Additionally, a registry of
outcomes after first trimester DAA exposure, similar to the antiretroviral pregnancy registry
(http://www.apregistry.com) is needed even with a larger study to determine the effect of exposure
early in pregnancy. Pregnant women with HCV prefer to be treated during pregnancy4. Jhavari, et al.
provides a strong call to action for us in the field and our NIH, FDA and industry partners to
determine the best way to get the evidence that is desperately needed.
1. Jhaveri R, Yee LM, Antala S, et al. Responsible Inclusion of Pregnant Individuals in Eradicating
Hepatitis C Virus. Hepatology 2021.
3. AASLD-IDSA. HCV testing and linkage to care. Recommendations for testing, managing, and
treating hepatitis C. https://www.hcvguidelines.org/unique-populations/pregnancy.
[Accessed on April 7, 2021]
4. Kushner T, Cohen J, Tien PC, et al. Evaluating Women's Preferences for Hepatitis C Treatment
During Pregnancy. Hepatol Commun 2018;2:1306-1310.