Safety, Efficacy of DAAs in Reproductive-Age Women Aid Prevention of Vertical HCV Transmission

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Hepatitis C virus (HCV) is on the rise among reproductive-aged adults, subsequently increasing rates of perinatal infection transmitted from mother to child. Thus, targeted treatment in this patient population will be crucial for meeting the World Health Organization (WHO)’s goal of eliminating viral hepatitis as a major public health problem by 2030.^1,2

Findings from a recent study published in Journal of Viral Hepatitis provide hope for this goal, demonstrating greater rates of sustained virologic response (SVR) following direct-acting antiviral (DAA) therapy with a more favorable safety profile among reproductive-age female patients than their male counterparts.¹

According to the US Centers for Disease Control and Prevention, in 2019, more than 63% of new HCV infections occurred among adults 20-39 years of age. Each year from 2011-2014, an estimated 29,000 HCV-infected patients gave birth and were at risk of transmitting infection to their child. Although most cases of infection can be cured with 8-12 weeks of oral therapy, curative treatment is not currently approved for use during pregnancy, underscoring the importance of screening for and treating infection in patients of reproductive age for both the safety of the mother and the child.³

“There is a gap regarding the detailed comparison of group characteristics, safety and effectiveness of treatment between women of childbearing age and men of the corresponding age,” Krystyna Dobrowolska, of the Institute of Public Health at Jan Kochanowski University in Poland, and colleagues wrote.¹

To assess the feasibility of eliminating HCV in women of reproductive age, investigators retrospectively analyzed the effectiveness of contemporary DAA therapy in a cohort of patients treated at 26 adult and pediatric hepatology centers in Poland. Data were collected retrospectively from a nationwide database as part of the EpiTer-2 multicenter project.¹

The study population comprised 7861 patients, including 3388 females and 4473 males with chronic HCV who were 15-49 years of age at the initiation of antiviral treatment. Investigators examined SVR, defined as undetectable HCV RNA at least 12 weeks after the end of treatment, additionally assessing patients’ HCV genotype, liver fibrosis, and type of treatment regimen. They also considered safety data, including modification or discontinuation of therapy as well as the occurrence of adverse events, severe adverse events, and death.¹

Among the cohort, investigators noted females were significantly less often infected with HCV genotype 3 compared to males (11.2% vs 15.7%), additionally less frequently presenting with comorbidities (40.5% vs 44.2%; P = .001) and taking comedications (37.2% vs 45.2%; P <.001). Hepatocellular cancer (HCC) and non-HCC tumors were more common in male patients, although the difference was only significant for HCC (0.5% vs 0.1%; P = .001). Males were also significantly more likely to have HIV co-infection (14% vs 6%; P <.001) and a history of liver transplantation (0.6% vs 0.3%; P = .02).¹

Regardless of the treatment type, SVR was reached significantly more frequently among female patients (98.8%) compared to male patients (96.8%). Further analysis revealed HCV genotype 3 and F4 fibrosis were independent risk factors for virological failure 12 weeks post-treatment, regardless of gender.¹

Regarding safety, treatment was carried out according to schedule in the majority of patients (98.5% of females and 98.1% of males) with a low chance of severe adverse events. Investigators pointed out women more commonly reported adverse events, the 2 most frequent of which were weakness/fatigue (6.9% vs 5.5%; P = .01) and headache (4.4% vs 2.4%; P <.001).¹

However, they noted death occurred more commonly in men (0.3% vs 0.1%; P = .03), although none was assessed by the treating physician as related to antiviral therapy. In the majority of cases, it was deemed to be the result of underlying advanced liver disease.¹

The retrospective nature of the study was pointed out by investigators as a potential limitation, raising concerns about the risk of entry errors, missing data, possible bias, and underestimation of the frequency of adverse events. Additionally, they noted data on contraceptive methods was not gathered, and information on potential risk factors for infection and reinfection was limited.¹

Nonetheless, they concluded: “Promising results of antiviral therapy provide hope for the microelimination of HCV infection in this population, which translates not only into reducing the health consequences of the infection but also preventing vertical transmission, which eliminates the risk of developing a severe disease not only in the woman but also in her child,” investigators concluded.¹

References:

1. ^{Dobrowolska K, Pawłowska M, Zarębska-Michaluk D, et al. Direct-acting antivirals in women of reproductive age infected with hepatitis C virus. J Viral Hepat. doi:10.1111/jvh.13936}
2. ^{World Health Organization. Global health sector strategy on viral hepatitis 2016-2021. Towards ending viral hepatitis. May 17, 2016. Accessed April 5, 2024. https://www.who.int/publications/i/item/WHO-HIV-2016.06}
3. ^{US Centers for Disease Control and Prevention. Test for Hepatitis C During Every Pregnancy. Know More Hepatitis. May 27, 2021. Accessed April 5, 2024. https://www.cdc.gov/knowmorehepatitis/hcp/Test-For-HepC-During-Pregnancy.htm}