Women of child-bearing age with hepatitis C showed early signs of menopause, putting them at greater risk for infertility, gestational diabetes and miscarriage, according to a recently published study. Sustained virologic response positively impacted these outcomes.
“We report that 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,” the researchers wrote. “It remains to be assessed whether antiviral therapy at a very early age can positively influence the occurrence of miscarriages and to prevent ovarian senescence. … The effect of treatment with new generation antiviral drugs could therefore be prospectively assessed with this dual purpose.”
To investigate the effects of HCV on ovarian function in women of childbearing age, the researchers prospectively enrolled 100 women with chronic liver disease and HCV, 50 women with chronic liver disease and hepatitis B, and 100 controls without liver disease at the University Hospitals of Modena, Turin and Naples.
Compared with controls, patients with HCV (P = .011) and those with HBV (P = .009) had lower anti-mullerian hormone (AMH) levels, which were otherwise similar between hepatitis groups. These levels indicate lower ovarian reserve and declining ovarian function. Patients with HCV had more frequently menopausal AMH levels compared with those with HBV (OR = 11.625; 95% CI, 2.651-50.97) and with controls (OR = 5.26; 95% CI, 2.169-12.82).
Among patients with HCV, the researchers found a correlation between AMH levels and hepatic grade (P = .041) and stage (P = .038), and an association with miscarriage occurrence in those with a median AMH level of 1 ng/mL (OR = 2.333; 95% CI, 1.029-5.292).
In analyzing the HCV and HBV cohorts together in comparison to the healthy controls, researchers associated only HCV infection (OR = 9.363; 95% CI, 2.569-34.123) with miscarriage.
Of those who underwent treatment for HCV, the independent factors for nonresponse included HCV genotype 1 (OR = 2.309; 95% CI, 1.119-1.19) and lower AMH levels (OR = 3.649; 95% CI, 1.123-11.904). AMH levels continued to decrease posttreatment among those who did not achieve SVR from baseline (3.4 vs. 2 ng/mL; P < .0001), whereas those who achieved SVR had a lower miscarriage rate than those who failed antiviral therapy (32.07% vs. 63.6%; OR = 0.255; 95% CI, 0.09-0.723). The researchers noted that all of the women received interferon-based therapies and therefore direct-acting antivirals should be further evaluated for their impact on fertility.
To compare their results, the researchers identified 6,805 U.S. women with HCV, 305 with HCV/HIV comorbidity, and 20,415 as hepatitis- and HIV-negative controls. Compared with controls, the women with HCV had higher probability of infertility (OR = 2.439; 95% CI, 2.13-2.794).
Pregnant patients in the U.S. cohort with HCV were also more likely to report premature birth (OR = 1.336; 95% CI, 1.059-1.685) and gestational diabetes (OR = 1.24; 95% CI, 1.019-1.51), and less likely to report live birth (OR = 0.754; 95% CI, 0.622-0.913). Additionally, patients with HCV/HIV comorbidity had an even higher risk for infertility (OR = 3.635; 95% CI, 2.467-5.357).
“A key result of our study concerns the association between HCV infection and risk of miscarriage,” the researchers concluded. “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.”
By Talitha Bennett