By Ahizechukwu C. Eke, MD, MPH
Assistant Professor in Maternal Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore
Dr. Eke reports no financial relationships relevant to this study.
SYNOPSIS: In this cost-effectiveness analysis study, the authors assessed the cost effectiveness of offering hepatitis C virus (HCV) antenatal rescreening to U.S. women who previously were screened HCV negative in a prior pregnancy. The authors demonstrated that universal HCV rescreening in pregnant women was cost-effective when compared to risk-based HCV screening, with an incremental cost of $47 (95% confidence interval [CI], $10 to $91) and an increase in quality-adjusted life years of 0.008 (95% CI, 0.001-0.015) per pregnant woman screened when compared to risk-based screening at baseline.
SOURCE: Chaillon A, Wynn A, Kushner T, et al. Cost-effectiveness of antenatal rescreening among pregnant women for hepatitis C in the United States. Clin Infect Dis 2020; April 13. doi: 10.1093/cid/ciaa362. [Online ahead of print].
Hepatitis C virus (HCV) is one of the major causes of liver cirrhosis, and a leading indication for liver transplantations.1 Very recently, the U.S. Preventive Services Task Force recommended that adults be screened for HCV once in their lifetime.2 With a prevalence rate of approximately 4% during pregnancy3 and a 5% potential for maternal to fetal transmission of HCV,4 as well as the advent of effective therapies,5 some obstetrical societies are recommending and encouraging universal HCV screening during pregnancy,6 with the aim of offering therapy during the postpartum period and after breastfeeding. However, there are no cost-effectiveness analyses to evaluate the efficiency of HCV rescreening in pregnant women who previously were screened in a prior pregnancy without evidence of HCV exposure. In this study, Challion and colleagues reported their findings on the cost-effectiveness of HCV prenatal rescreening in U.S. women who previously screened negative during a prior pregnancy and without evidence of past HCV exposure.7 The baseline population included pregnant women with a mean age of 30 years and a mean interpregnancy interval of three years.
To parameterize their Markov model of HCV progression and treatment, the authors made a number of assumptions. First, because of the absence of data for HCV prevalence in pregnant women who tested negative to HCV in a prior pregnancy, the authors estimated HCV prevalence by multiplying the estimated proportion of pregnant women who were injection drug users (IDU) with the prevalence of HCV among women who had screened negative to HCV antibodies in their prior pregnancy but remained at high risk for HCV. Second, they estimated a 17/100 person-years incidence of HCV infection among females who use injection drugs. Third, they estimated a 38% spontaneous HCV clearance rate among women; and fourth, they estimated that 1.25% of pregnant women would use injection drugs at baseline. Fifth, they estimated that all pregnant women who screened HCV negative during a prior pregnancy were assumed to have a Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) F0 stage. Sixth, they assumed a 75% per year loss to follow up after a diagnosis of HCV is made during pregnancy. The authors assumed that all women incorporated into the model were secundigravidas, with a fertility rate of 1.7 births per woman in 2018.7
A two-way sensitivity analysis was performed to evaluate uncertainties in the base model by varying two parameters (IDU and interpregnancy interval) to change simultaneously, and examining the potential effect of such variation on the model’s result within a specified range. The authors varied the prevalence of IDU among pregnant women during a subsequent pregnancy without evidence of HCV infection and interpregnancy interval between 0.25% and 1.5% and one to four years, respectively. One-way analyses also were performed by varying single parameters in the model, one at a time, including fibrosis progression rate (0.95/year vs. 0.11/year) and treatment eligibility based on staging (no restrictions based on METAVIR stages vs. treatment restriction until at least METAVIR stage F1). Probabilistic sensitivity analysis also was performed, with parameters sampled randomly from distributions to generate 10,000 iterations. Mean incremental cost-effectiveness ratios (ICERs) were used to express cost-effectiveness under a willingness to pay threshold of $50,000/quality-adjusted life year (QALY) gained. Costs were expressed in 2019 U.S. dollars, and health utilities were expressed in QALYs and discounted at 3%/year.
The authors demonstrated that universal HCV rescreening in pregnant women was associated with an incremental cost of $47 (95% confidence interval [CI], $10 to $91) and an increase in QALY of 0.008 (95% CI, 0.001-0.015) per pregnant woman screened when compared to risk-based screening at baseline. Rescreening for HCV during a second pregnancy was cost-effective compared to rescreening based on risk factors, with a mean ICER of $6,000 per QALY gained, which is below the willingness to pay threshold of $50,000/QALY gained. Universal screening for HCV during pregnancy remained favored over risk-based screening in one-way, two-way, and probability sensitivity analyses, including in situations of low IDU (0.25%) and short interpregnancy interval (one year). Sensitivity analyses results also remained robust to low fibrosis progression rates and treatment restrictions by fibrosis status.
Cost-effectiveness analysis is a major tool used by health policy analysts to predict costs and health outcomes that may be associated with various screening and treatment modalities, with the goal of making healthcare decisions from economic evaluation that are inexpensive, yet effective. Most cost-effectiveness analyses incorporate a number of assumptions in their data, and these can introduce uncertainties in the results.8 Sensitivity analysis is a good way to measure and evaluate uncertainties in cost-effectiveness data, since sensitivity analyses examine the potential effect of a wide range of uncertainties within a model.8 Results of cost-effectiveness analyses are best reported as an ICER, with a willingness to pay threshold of $50,000 being the most used and cited in cost-effectiveness analysis literature.9,10
The authors demonstrated that rescreening for HCV in pregnant women in the United States without prior history of HCV infection or exposure was cost-effective compared to rescreening based on risk factors alone. The authors argued further that if rescreening of this low-risk population for HCV is cost-effective, then rescreening of pregnant women at higher risk for HCV (active IDUs) would be even more cost-effective during pregnancy. Although the finding from this study is impressive and important for health policy decision-making during pregnancy, it is important to keep in mind the intricacies of universal testing, and put things into perspective when advocating for universal screening, as described by the Wilson and Jungner criteria.11 Wilson and Jungner’s criteria, when applied to HCV screening, imply that HCV should be an important health problem; should have a latent stage, and the natural history of HCV should be adequately understood; should have a suitable testing algorithm for diagnosis and treatment that are readily available, with an agreed policy on the population that would benefit from therapy; should involve a continuous process for HCV case finding rather than just a one-time venture; and should have an economically plausible total cost of finding a case of HCV during pregnancy. The last two criteria more specifically support universal testing and the findings from this study for rescreening of HCV during pregnancy in low-risk pregnant patients so they could benefit from therapeutic interventions for hepatitis C during the postpartum period.
In conclusion, HCV universal rescreening is not yet a widely accepted practice during pregnancy. Until more data are available, universal rescreening of HCV during pregnancy in low-risk women who tested negative to HCV in a previous pregnancy is not advised or recommended.
- Bhamidimarri KR, Satapathy SK, Martin P. Hepatitis C virus and liver transplantation. Gastroenterol Hepatol (NY) 2017;13:214-220.
- US Preventive Services Task Force; Owens DK, Davidson KW, et al. Screening for hepatitis C virus infection in adolescents and adults: US Preventive Services Task Force recommendation statement. JAMA 2020; Mar 2. doi: 10.1001/jama.2020.1123. [Online ahead of print].
- Prasad MR, Honegger JR. Hepatitis C virus in pregnancy. Am J Perinatol 2013;30:149-159.
- Ragusa R, Corsaro LS, Frazzetto E, et al. Hepatitis C virus infection in children and pregnant women: An updated review of the literature on screening and treatments. AJP Rep 2020;10:e121-e127.
- Hong J, Wright RC, Partovi N, et al. Review of clinically relevant drug interactions with next generation hepatitis C direct-acting antiviral agents. J Clin Transl Hepatol 2020;8:322-335.
- The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Management of hepatitis C in pregnancy. March 2020. https://ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women%27s%20Health/Statement%20and%20guidelines/Clinical-Obstetrics/Management-of-Hepatitis-C-in-Pregnancy-(C-Obs-51).pdf?ext=.pdf#:~:text=Among%20women%20already%20pregnant%20with,special%20expertise%20in%20infectious%20disease
- Chaillon A, Wynn A, Kushner T, et al. Cost-effectiveness of antenatal rescreening among pregnant women for hepatitis C in the United States. Clin Infect Dis 2020; Apr 13;ciaa362. doi: 10.1093/cid/ciaa362. [Online ahead of print].
- Ryder HF, McDonough C, Tosteson AN, Lurie JD. Decision analysis and cost-effectiveness analysis. Semin Spine Surg 2009;21:216-222.
- Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness – the curious resilience of the $50,000-per-QALY threshold. N Engl J Med 2014;371:796-797.
- Hirth RA, Chernew ME, Miller E, et al. Willingness to pay for a quality-adjusted life year: In search of a standard. Med Decis Making 2000;20:332-342.
- Wilson JMG, Jungner G, World Health Organization. Principles and Practice of Screening for Disease. World Health Organization;1968.