By Rebecca H. Allen, MD, MPH
Associate Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI
Dr. Allen reports she receives grant/research support from Bayer and is a consultant for Merck.
In this cost-effectiveness analysis using Markov modeling, investigators found that universal antenatal screening for hepatitis C was cost-effective, with a mean incremental cost-effectiveness ratio of approximately $3,000 per quality-adjusted life years gained compared to risk-based screening.
Chaillon A, Rand EB, Reau N, Martin NK. Cost-effectiveness of universal hepatitis C virus screening of pregnant women in the United States. Clin Infect Dis 2019; Jan. 28. doi: 10.1093/cid/ciz063. [Epub ahead of print].
In this Markov model cost-effectiveness analysis, the authors compared universal antenatal screening for hepatitis C followed by treatment after pregnancy to risk-based screening (the current practice in the United States). As with most cost-effectiveness modeling, assumptions were made based on national estimates and knowledge of disease.
Chaillon et al assumed an average age of 27 years for pregnant women and a chronic hepatitis C virus (HCV) prevalence of 0.73%, with annual loss to follow-up rates after HCV diagnosis of 12%. They estimated that 18% of HCV-infected pregnant women have been diagnosed previously and linked to care. The current risk-based testing and linkage rate per year was estimated to be 5%, and the cost of anti-HCV and HCV RNA confirmatory lab testing was based on the 2018 national fee schedule. Drug costs were estimated to be $25,000 per treatment course, with 90% sustained virological response. They classified chronic liver disease using the METAVIR system (F0 = no fibrosis, F1 = portal fibrosis without septa, F2 = few septa, F3 = numerous septa without cirrhosis, F4 = cirrhosis) and based fibrosis distribution and liver disease stage transition rate per year on U.S. national estimates for women. They did not assume treatment restrictions by fibrosis stage, and calculated annual costs for nontreatment medical expenses among HCV-infected patients by stage.
The authors also calculated a mean incremental cost-effectiveness ratio (mean incremental costs divided by the mean incremental quality-adjusted life years) for antenatal screening compared to risk-based screening. The assumed willingness to pay threshold was $50,000 per quality-adjusted life year gained. They also estimated the effect of routine antenatal HCV screening on the U.S. population.
Chaillon et al found that the incremental cost of universal hepatitis C screening was $53.20 for the testing, and the incremental increase in quality-adjusted life years was 0.019 per pregnant woman screened compared to risk-based screening. That calculated to a mean incremental cost-effectiveness ratio of $2,826 per quality-adjusted life years gained compared to risk-based screening, falling below the $50,000 willingness-to-pay threshold. Sensitivity analyses showed that universal screening still was cost-effective under different treatment eligibility scenarios, different prevalence rates of HCV, different fibrosis progression rates, 85% vs. 90% sustained virological response, higher proportion of women already diagnosed and linked at baseline (40%), higher loss to follow-up rates (50%), lower liver transplant costs, higher background testing rates, and lower proportion of cirrhosis in the baseline cohort. The estimated effect to the U.S. population was that screening 5.04 million pregnant women in 2018 would result in the detection and treatment of 33,000 women overall, with an incremental detection and treatment of 7,000 women.
COMMENTARY
There has been a debate as to whether we should screen all pregnant women for HCV infection in the United States.1 HCV causes chronic liver disease in 75% to 85% of those infected and can progress to liver failure and death. The incidence of HCV infection has been increasing among young adults because of the opioid epidemic.2 At the same time, we now finally have treatments (direct-acting antiviral therapies) that are more than 90% effective in clearing the virus. Based on testing recommendations from the Centers for Disease Control and Prevention and endorsed by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine (SMFM), the following prenatal patients should be screened for HCV:3
- Women who have been injection drug users, even those who injected only once;
- Women who received clotting factor concentrates made prior to 1987;
- Women who received blood transfusions or solid organ transplants before July 1992;
- Chronic hemodialysis patients;
- Women who have been exposed to HCV, such as healthcare workers after needle sticks involving HCV-positive blood and those who have received blood or organs from a donor who tested HCV-positive;
- Women with HIV infection;
- Women seeking evaluation or care for sexually transmitted infections;
- Incarcerated women;
- Women who use intranasal drugs;
- Women who have had a tattoo or piercing at an unregulated facility without strict infection control policies.
The main reason the SMFM has not recommended universal screening is because no treatments are safe for use in pregnant women; therefore, there is no way to affect vertical transmission rates.3 As a result, any woman testing positive would have to wait until the postpartum period to initiate therapy. Additionally, there are concerns regarding its cost-effectiveness and the low prevalence of HCV infection. Nevertheless, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America recently called for universal screening of pregnant women.4 Arguments in favor of universal screening include using prenatal care as an opportunity to diagnose HCV in reproductive-age women, as pregnant women typically are insured and then can be linked to HCV care postpartum (if their insurance continues to be active after the postpartum period). With a vertical transmission rate of about 5%, the infants of pregnant women with HCV also could be identified and tested. Furthermore, the earlier identification of women infected with HCV would allow treatment before the next pregnancy, reducing vertical transmission. Finally, studies have shown that the risk-based screening, as currently practiced, is not effective.4
The outcomes of cost-effectiveness analyses depend highly on the assumptions in the model. Chaillon et al demonstrated that universal screening is cost-effective with the newer drug prices for direct-acting antiviral medications. Another recent study using a different cost-effectiveness model also showed that universal prenatal screening for HCV was cost-effective.5 This model estimated the mean incremental cost-effectiveness ratio to be $41,000 per quality-adjusted life years gained compared to risk-based screening. For comparison, the mean incremental cost-effectiveness ratio for gestational diabetes screening is estimated at $20,000 and postpartum depression screening is $14,000. In terms of what is considered a worthwhile investment, the willingness-to-pay threshold per quality-adjusted life years gained for healthcare interventions varies in the literature from $50,000 to $100,000. Basically, a willingness-to-pay threshold is the amount the healthcare system (patient, insurance company, or society) would be prepared to pay for a health benefit. Therefore, both studies calculated an incremental cost-effectiveness ratio less than $50,000 per quality-adjusted life years gained, indicating that universal prenatal screening is cost-effective.
Despite the lack of a treatment available during pregnancy, and given that testing for HCV is not too expensive and can be added to prenatal labs easily, I suspect this will become part of the prenatal lab panel in the future. This would parallel the transition that HIV testing took, from risk-based to universal screening in prenatal care. Some changes to obstetric practice would occur if a patient tested positive for HCV, such as avoiding internal fetal monitoring, prolonged rupture of membranes, and episiotomy in managing labor.3 Additionally, the infant could be tested after birth. Testing would change management even if the patient did not follow up postpartum for HCV treatment. Nevertheless, it remains to be seen if SMFM will change its recommendations in its next guideline revision.
REFERENCES
- Prasad MR. Hepatitis C virus screening in pregnancy: Is it time to change our practice? Obstet Gynecol 2016;128:229-230.
- Koneru A, Nelson N, Hariri S, et al. Increased hepatitis C virus (HCV) detection in women of childbearing age and potential risk for vertical transmission - United States and Kentucky, 2011-2014. MMWR Morb Mortal Wkly Rep 2016;65:705-710.
- Society for Maternal Fetal Medicine. Hepatitis C in pregnancy: Screening, treatment, and management. SMFM Consult Series #43. Available at: https://www.smfm.org/publications/248-smfm-consult-series-43-hepatitis-c-in-pregnancy-screening-treatment-and-management. Accessed March 27, 2019.
- The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Available at: https://www.hcvguidelines.org/sites/default/files/full-guidance-pdf/HCVGuidance_May_24_2018b.pdf. Accessed March 27, 2019.
- Tasillo A, Eftekhari Yazdi G, Nolen S, et al. Short-term effects and long-term cost-effectiveness of universal hepatitis C testing in prenatal care. Obstet Gynecol 2019;133:289-300.
