HCV Vertical Transmission in Pregnancy: New Horizons in the Era of DAAs
Kanninen TT, et al.
Hepatology. 2015 Dec;62(6):1656-8.

Routine prenatal hepatitis C virus (HCV) screening is not recommended in women lacking risk factors for infection. The prevalence of HCV infection in pregnancy has been estimated to be similar to the reported 0.5%-1.4% seropositivity in low-risk blood donors. Vertical transmission rates of HCV have been reported between 2% and 10%. Maternal risk factors reported to be associated with an increased rate of vertical HCV transmission include higher maternal HCV viral titer, prolonged membrane rupture during labor (6 hours or longer), and use of internal fetal monitoring during labor. Mothers with undetectable plasma HCV-RNA levels rarely vertically transmit HCV.

HCV treatment was usually delayed after pregnancy given limited experience with the use of interferon (IFN) in pregnancy and the absolute contraindication for ribavirin (RBV) use.

Given that maternal viremia has been linked to vertical neonatal transmission, the use of DAAs may considerably lower HCV vertical transmission in pregnancy and warrant future studies. These new emerging therapies may present a new avenue to preventing HCV neonatal transmission. DAAs have less severe adverse affects (e.g., headache and fatigue) and a shorter duration of therapy.

Currently, experience with any of these new DAAs in human pregnancy is nonexistent.

Sofosbuvir and ledipasvir are both category B drugs, given there was no evidence of fetal harm in animal studies. However, simeprevir is a category C medication in monotherapy. Animal studies in mice have showed significantly reduced fetal weights, increased fetal skeletal variations, in utero fetal losses, and early maternal deaths at high simeprevir exposures. The safety profiles of each one of the new HCV medications will indisputably have to be individually examined before evaluating a potential use in HCV in pregnancy.

Current screening protocols in pregnancy do not recommend universal HCV screening given the lack of effective treatments in preventing maternal-neonatal transmission. However, the 2%-10% reported vertical transmission rate of HCV and potential negative maternal outcomes in HCV infections in pregnancy is not an insignificant quantity. The emergence of new routes of therapy offer the possibility to examine further methods of lowering these risks to maternal-fetal outcome and may provide new support for universal HCV screening in pregnancy provided their effectiveness.

Expert's Commentary

« The expanding armamentarium of direct acting antiviral combinations for treatment and cure of HCV has provided great benefit to a growing number of special populations. Historically special populations included pregnancy, breast feeding, pediatrics, geriatric, hepatic and renal impairment, HIV co-infection and solid organ transplant. With the recent approvals of ledipasvir/sofosbuvir, paritaprevir/ritonavir/ombitasvir + dasabuvir, simeprevir, daclatasvir, and elbasvir/grazoprevir, HIV infection is no longer listed as a special population and in fact all of these regimens are approved in patients with HIV-infection. Furthermore, two of these regimens are approved in solid organ transplant and one is approved in patients with severe renal impairment, including those on hemodialysis. Yet, in light of these great advancements there are special populations who seem to have been left out and those include children and pregnant women. Given the likelihood that these regimens would be highly efficacious in both preventing vertical transmission and curing the mothers simultaneously we must advocate for moving the field forward for women and children. In addition, an active approach to reaching young women prior to pregnancy would help stave this epidemic. Most current approved DAA regimens are safe in pregnancy in animal models (simeprevir and daclatasvir are the only two with evidence of fetal harm in animal models). We now need to focus on those special populations who have been left behind so that the benefit of curative DAA therapies can be realized for all »

Dr Susanna Naggie