Women of childbearing age with hepatitis C virus (HCV) have fewer live births as well as greater risk of infertility, gestational diabetes, pre-eclampsia, and miscarriage, according to researchers in Italy. Premature ovarian senescence appears to be the cause of these problems, but early antiviral therapy might be part of the solution, the researchers reported in the Journal of Hepatology.
"The relationship between HCV infection and reproductive status in women is much deeper and broader than previously thought, with profound consequences for reproductive function confirmed in cohorts from different countries,” wrote corresponding author Erica Villa, MD, Professor of Gastroenterology at University of Modena and Reggio Emilia, in Modena, Italy, and colleagues.
In earlier research, Dr. Villa and colleagues found that premenopausal women who were HCV-positive already had menopausal levels of anti-Müllerian hormone (AMH)—a reliable marker of ovarian reserve. This suggested to the researchers that reproductive function could be affected in younger women with HCV.
For this study, the researchers recruited 100 women of childbearing-age who had HCV and chronic liver disease, as well as 50 age-matched women with hepatitis B virus (HBV) and chronic liver disease. The researchers also recruited 100 healthy women without liver disease as a control group. Women in all three groups were assessed for age, reproductive status, and serum levels of AMH.
The researchers also compared their study data with the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) study as well as a large US insurance database.
Results showed that HCV-positive women had significantly lower levels of AMH than both HBV-positive women and uninfected controls—and this finding was significantly associated with a notably high rate of miscarriage in HCV-positive women.
Also, the fertility rate for HCV-positive women of childbearing years was 0.7 compared with 1.37 for uninfected women in the same age range.
“Regardless of age, compared to the general Italian population, HCV-positive women enrolled in the study had an excessively high miscarriage rate and an unfavorable ratio between pregnancy attempts and completed pregnancies compared to uninfected controls or HBV-infected women,” the authors wrote.
However, the underlying mechanisms for this excessively high rate are unclear, they added.
“These results point to a specific relationship between HCV infection, ovarian function, and reproductive efficiency, suggesting that the premature ovarian senescence observed in HCV-positive women, as indicated by the early and significant AMH decline, has a profound effect on reproductive function,” the authors wrote.
They noted that the timing of antiviral treatment needs further study to determine whether it could reduce the rate of miscarriages. In this study, for instance, HCV-positive women who achieved a sustained virologic response to antiviral treatment also experienced a stabilization of their AMH levels. They also had a lower rate of miscarriage than women who failed antiviral therapy and whose AMH levels continued to decline.
“It remains to be assessed whether antiviral therapy at a very early age can positively influence the occurrence of miscarriages and prevent ovarian senescence, as the latter has a much broader health implication than simply preservation of fertility,” Dr. Villa and colleagues concluded. “The effect of treatment with new generation antiviral drugs could, therefore, be prospectively assessed with this dual purpose.”