Obstetrics & Gynecology:
Contents: Original Research
Cost-Effectiveness of Testing Hepatitis B–Positive Pregnant Women for Hepatitis B e Antigen or Viral Load
Fan, Lin PhD; Owusu-Edusei, Kwame Jr PhD; Schillie, Sarah F. MD, MPH; Murphy, Trudy V. MD
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
Corresponding author: Lin Fan, PhD, Centers for Disease Control and Prevention, 1600 Clifton Road, MS G-37, Atlanta, GA 30333; e-mail: Wqm3@cdc.gov.
Presented at “INFORMS 2nd Conference on Healthcare,” June 23–26, 2013, Chicago, Illinois.
Financial Disclosure The authors did not report any potential conflicts of interest. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the Centers for Disease Control and Prevention.
OBJECTIVE: To estimate the cost-effectiveness of testing pregnant women with hepatitis B (hepatitis B surface antigen [HBsAg]-positive) for hepatitis B e antigen (HBeAg) or hepatitis B virus (HBV) DNA, and administering maternal antiviral prophylaxis if indicated, to decrease breakthrough perinatal HBV transmission from the U.S. health care perspective.
METHODS: A Markov decision model was constructed for a 2010 birth cohort of 4 million neonates to estimate the cost-effectiveness of two strategies: testing HBsAg-positive pregnant women for 1) HBeAg or 2) HBV load. Maternal antiviral prophylaxis is given from 28 weeks of gestation through 4 weeks postpartum when HBeAg is positive or HBV load is high (108 copies/mL or greater). These strategies were compared with the current recommendation. All neonates born to HBsAg-positive women received recommended active-passive immunoprophylaxis. Effects were measured in quality-adjusted life-years (QALYs) and all costs were in 2010 U.S. dollars.
RESULTS: The HBeAg testing strategy saved $3.3 million and 3,080 QALYs and prevented 486 chronic HBV infections compared with the current recommendation. The HBV load testing strategy cost $3 million more than current recommendation, saved 2,080 QALYs, and prevented 324 chronic infections with an incremental cost-effectiveness ratio of $1,583 per QALY saved compared with the current recommendations. The results remained robust over a wide range of assumptions.
CONCLUSION: Testing HBsAg-positive pregnant women for HBeAg or HBV load followed by maternal antiviral prophylaxis if HBeAg-positive or high viral load to reduce perinatal hepatitis B transmission in the United States is cost-effective.
An estimated 5,000–8,000 persons who become infected with hepatitis B virus (HBV) develop chronic HBV annually.1 Perinatal HBV exposure is an important source of chronic HBV. Approximately 24,000 neonates are born to mothers positive for hepatitis B surface antigen (HBsAg) annually in the United States.2,3 Without intervention, more than 30% (approximately 7,200) of these neonates will become HBV-infected.4 Approximately 90% of HBV-infected neonates will develop chronic HBV4 and have a 25% risk of premature death from liver failure or hepatocellular carcinoma.1,3,4 Active-passive immunoprophylaxis with hepatitis B vaccination and hepatitis B immune globulin potentially reduces chronic HBV infections to 5% or less (approximately 1,200) of perinatally exposed neonates. In this scenario, almost all of the neonates with HBV infection are born to pregnant women with high HBV load, the most important factor predicting breakthrough infections. High HBV load is measured in peripheral blood directly by quantifying the amount of HBV DNA in serum or is estimated by detecting hepatitis B e antigen (HBeAg), which strongly correlates with high HBV load.5–7
Maternal antiviral prophylaxis during pregnancy (eg, lamivudine, telbivudine, or tenofovir), in addition to active-passive immunoprophylaxis for neonates, might prevent 70% of perinatal breakthrough infections, possibly by suppressing HBV replication.8–11 However, maternal antiviral prophylaxis is not currently the standard of care in the United States.1 The objective of this study was to estimate the cost-effectiveness of testing for HBeAg or HBV load among HBsAg-positive pregnant women followed by maternal antiviral prophylaxis if indicated in addition to the recommended active-passive immunoprophylaxis for their neonates.
MATERIAL AND METHODS
Based on the 2010 estimate of live births in the United States,12 we used a birth cohort of 4 million neonates. We constructed a decision tree model to estimate the costs and effects of two sequential testing strategies:
1. Sequential HBeAg testing: among HBsAg-positive pregnant women, test for HBeAg followed by maternal antiviral prophylaxis if positive
2. Sequential HBV load testing: among HBsAg-positive pregnant women, determine HBV load followed by maternal antiviral prophylaxis if indicated for high HBV load.
In these two strategies, all women are routinely screened for HBsAg, and all neonates born to HBsAg-positive women receive recommended active-passive immunoprophylaxis with a hepatitis B vaccine dose and hepatitis B immune globulin starting within 12 hours of birth followed by completion of the hepatitis B vaccine series. We compared the costs and effects of the two sequential maternal testing strategies with those of the current recommendation13: HBsAg screening for all pregnant women. Neonates born to HBsAg-positive women receive active-passive immunoprophylaxis.13 Neonates born to HBsAg-negative women receive a “birth dose” of hepatitis B vaccine before hospital discharge (within 72 hours of birth) followed by completion of the hepatitis B vaccine series.13 We also estimated the costs and effects of two additional strategies:
1. No intervention: no HBsAg screening for pregnant women and no prophylaxis or hepatitis B vaccination for their neonates
2. Neonate vaccination only: no HBsAg screening for pregnant women and a complete hepatitis B vaccine series starting within 72 hours of birth without hepatitis B immune globulin.
We constructed a Markov model to estimate the lifetime cost (in 2010 U.S. dollars) and effects (quality-adjusted life-years [QALY]) associated with acquiring chronic HBV infection for neonates. The Markov model of chronic HBV infection includes a set of health states: inactive carrier, active chronic HBV infection, cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and death.14 Life expectancy is approximately 78 years in the United States; we used a life cycle of 80 years.15 Like in previous studies, the natural history of chronic HBV in a general population is used to model the natural history of perinatally acquired chronic HBV, which is not well described.16 Most perinatally infected neonates remain in the immune-tolerant stage during childhood; although significant complications can occur at a young age, most do not occur until adulthood. Therefore, we assumed that complications start at age 20 years, like in previous studies.17,18
The baseline parameter values (including plausible ranges) used in the decision tree and Markov model are summarized in Table 1. The overall prevalence of HBsAg among pregnant women was estimated at 0.6%.2,3,19 Without intervention, we estimated an overall perinatal transmission rate of 35.7% for HBsAg-positive women combining the proportional transmission rates for HBeAg-positive and HBeAg-negative women.4,6,20 We considered a three-dose hepatitis B vaccination series (without hepatitis B immune globulin) to be 72% efficacious for preventing perinatal infection.20 The overall perinatal transmission rate was approximated at 5% with active-passive immunoprophylaxis.7,21,22 We assumed 90% of HBV-infected neonates will develop chronic HBV.1,4,17
Table 1-a Parameter ...Image Tools
The prevalence of HBeAg and high viral load, and perinatal transmission rates among neonates, were based on ranges reported in the literature and the assumption that, without antiviral prophylaxis during pregnancy, transmission rates for sequential HBeAg testing and sequential HBV load testing had to equal the transmission rate with the current recommendation. For example, the transmission rate was estimated at 5% under the current recommendation. If the prevalence of HBeAg positivity among HBsAg-positive women is 30%, and the perinatal transmission rate for HBeAg-positive women is 15%,6,23–26 then the prevalence of HBeAg negativity among HBsAg-positive women is 70%, and the perinatal transmission rate for neonates born to HBeAg-negative women would be 0.71%, because the overall perinatal transmission rate remains 5% ([30%×15%]+[70%×0.71%]=5%).
Table 1-b Parameter ...Image Tools
We defined a high HBV load as 108 copies/mL or greater. The perinatal transmission rates start to increase as the HBV load reaches 106 copies/mL or greater.7 Because prevalence data for women with HBV load higher or lower than 106 copies/mL are limited, we used 106 copies/mL or greater as the lower limit of value defined as high viral load for sensitivity analyses.7,18,25,27,28 Approximately 10–30% of persons with chronic HBV have viral load 108 copies/mL or greater.7,25–27 Consequently, we chose 20% prevalence as our base estimate. The estimated perinatal transmission rates for pregnant women with HBV load 108 copies/mL or greater ranges from 7 to 32%; we used 15% as the base estimate.7,25–27
Meta-analyses suggest that in addition to active-passive immunoprophylaxis, maternal antiviral prophylaxis can reduce perinatal transmission by 68% (range 37–85%).8,29 We chose a 50% reduction rate as our base estimate. We assumed all pregnant women with HBeAg or high HBV load will accept antiviral prophylaxis (ie, a 4-month course of lamivudine, 100 mg orally once daily from 28 weeks of gestation through 4 weeks postdelivery18).
The disease-specific mortality rate and annual transition rates among chronic HBV infection health states were estimated from the natural history of hepatitis B in the general population.1,27,30–35 We assumed all cases of cirrhosis come from chronic HBV, and all decompensated cirrhosis come from cirrhosis (Table 1).
Costs and QALYs were derived from the literature.1,18,27,30–34,36 The cost was adjusted to reflect 2010 U.S. dollars using the medical care component of the consumer price index for All Urban Consumers.37 We conducted the analyses from the health care system's perspective. Data describing the societal costs such as productivity loss and caregivers' costs were not available. Therefore, we used the health care system's costs to estimate the cost to save 1 QALY. The base cost for antiviral prophylaxis was for a 4-month course of lamivudine. Depending on the choice of antiviral drugs, the cost for a 4-month course ranges from $1,000 to $4,000.1,18,30,32 We assumed a $100 cost for annual monitoring (ie, office visits, HBsAg, and HBeAg tests)30 for chronic HBV in the first 20 years for those infected through perinatal transmission (Table 1).
We performed one-way sensitivity analyses on each variable and ranked the range of incremental cost-effectiveness ratios to determine the most influential variables. We then used these variables to conduct a multiway probabilistic sensitivity analysis (ie, a Monte Carlo analysis with 10,000 simulations) to investigate how changes in these variables would affect the estimated incremental cost-effectiveness ratio (measured in dollars per QALY saved). Parameters of the distribution for the variables (such as α and β for β distribution and μ and λ for lognormal distribution) are not available; therefore, we used a triangular distribution, which requires the minimum, likeliest, and maximum values for all variables.
Both outcomes (costs and QALYs) were discounted at a 3% annual rate.38 We calculated the incremental cost-effectiveness ratio for each strategy compared with the current recommendation. TreeAge Pro 2012 was used to build the decision tree and Markov model. Institutional review board approval was not required because we used secondary data for this study.
We determined the number of neonates with perinatal HBV infection and their lifetime complications for each of the interventions compared with the base case (Table 2). The no intervention strategy had the highest number of children (7,711) who developed chronic HBV. Among the 7,711 children, 1,316 would develop hepatocellular carcinoma, 1,227 would develop decompensated cirrhosis, and 251 would need a liver transplant. The infant vaccination only strategy had the second highest number of infants who developed chronic HBV and the sequential HBV load testing strategy using 106 copies/mL or greater as the cutoff for high viral load had the lowest number of children who developed chronic HBV (Table 2). Compared with no intervention and infant vaccination only, the current recommendation was cost-effective with an incremental cost-effectiveness ratio of $7,146 and $6,358 per QALY saved, respectively (Table 3). Compared with the current recommendation, sequential HBeAg testing saved 3,080 QALYs and $3.3 million (cost-saving), and the sequential HBV load testing using 108 copies/mL or greater saved 2,080 QALYs with a cost of $3.3 million (incremental cost-effectiveness ratio: $1,583 per QALY saved). Sequential HBeAg testing dominated sequential HBV load testing using 108 copies/mL or greater with 1,000 QALYs and $6.6 million saved.
Results for the one-way sensitivity analyses are presented in Table 4. Both strategies remained cost-effective throughout the range of values used in the sensitivity analyses. The most influential variables were the cost and efficacy of antiviral prophylaxis. When the cost of antiviral prophylaxis increased from $800 to $4,000, the incremental cost-effectiveness ratios for sequential HBeAg testing and sequential HBV load testing using 108 copies/mL or greater increased to $4,540 and $7,172 per QALY saved, respectively. When the antiviral-associated reduction of perinatal transmission decreased from 80% to 20%, the incremental cost-effectiveness ratios for sequential HBeAg testing and sequential HBV load testing increased to $4,708 and $11,167 per QALY saved, respectively. Other influential variables affecting the incremental cost-effectiveness ratios included lifetime chronic HBV costs and QALY, perinatal transmission rate, the cost of HBV load testing, and the proportion of women receiving antiviral prophylaxis when this strategy is applied.
Results of the probabilistic sensitivity analysis focusing on the influential variables (from Table 4) are presented in Table 5. Both strategies remained cost-effective compared with the current recommendation. The maximum incremental cost-effectiveness ratios were $20,796 and $29,708 per QALY saved for sequential HBeAg testing and sequential HBV load testing, respectively.
We also examined 106 copies/mL or greater as the value defining high HBV load. Compared with the current recommendation, sequential HBV load testing with 106 copies/mL or greater HBV load prevented 551 chronic HBV infections, 94 hepatocellular carcinoma cases, 83 decompensated cirrhosis cases, 18 liver transplants, and saved 3,440 QALYs at a cost of $8.0 million. Applying 106 copies/mL or greater to define a high HBV load saved 360 more QALYs with approximately $11.3 million in costs compared with sequential HBeAg testing (incremental cost-effectiveness ratio: $31,389 per QALY) and saved 1,360 more QALYs with approximately $4.7 million in costs compared with sequential HBV load testing with 108 copies/mL or greater defining high viral load (incremental cost-effectiveness ratio: $3,456 per QALY). In the one-way and multiway probabilistic sensitivity analyses, sequential HBV load testing with 106 copies/mL or greater remained cost-effective compared with the current recommendation (Tables 2–5).
Our study demonstrated that either sequential HBeAg testing or sequential HBV load testing was cost-effective under a wide range of assumptions compared with the current recommendation. The cost-effectiveness of sequential HBeAg testing and sequential HBV load testing relies on several factors, including the cost and efficacy of maternal antiviral prophylaxis and lifetime costs associated with chronic HBV infection.
Several studies have concluded that maternal antiviral prophylaxis among HBsAg-positive women during pregnancy, in addition to active-passive immunoprophylaxis for the neonate, is cost-effective or cost-saving.1,18,27 The purpose of sequential HBeAg testing and HBV load testing is to identify HBsAg-positive women whose neonates have the highest risk for perinatal transmission. If maternal antiviral prophylaxis is cost-effective in preventing perinatal HBV infection among the general population of HBsAg-positive women, identification of the highest risk population using HBeAg testing or HBV load testing is likely to be cost-effective, because the cost of testing for HBeAg or DNA is small compared with the cost of antiviral prophylaxis during pregnancy.
Several antivirals (ie, lamivudine, tenofovir, and telbivudine) reduce HBV viral load and might reduce perinatal HBV transmission.9–11 Although lamivudine is the most studied maternal antiviral for preventing HBV perinatal transmission, tenofovir or telbivudine has been considered because they effectively reduce HBV load with lower rates of drug resistance than lamivudine.18,39,40 We do not expect the choice of antiviral agent alone to change the cost-effectiveness given the results from sensitivity analyses.
Although HBeAg testing is less expensive than HBV load testing, HBeAg testing can miss a small proportion of women with negative HBeAg but high HBV load.41 In our baseline assumption, sequential HBeAg testing dominated sequential HBV load testing using 108 copies/mL or greater as the cutoff value for high viral load (lower cost, higher QALY saved for HBeAg testing). However, results of a comparison between the two strategies depends on the cutoff for high HBV load, the costs of HBeAg and HBV load testing, the prevalence of HBeAg and high HBV load among HBsAg-positive pregnant women, and the perinatal transmission rates. Sequential HBV load testing using 106 copies/mL or greater has an incremental cost-effectiveness ratio of $31,389 per QALY saved compared with sequential HBeAg testing.
This study has several limitations. First, all limitations associated generally with models are applicable because our model is a simplification of real-world events. Second, the validity of models and the results depend largely on the availability and reliability of the data. We used parameter values that varied substantially. As a result of lack of data on the parameters of the distribution for each variable, we used a triangular distribution for all variables. Using different distributions might change the results of the probabilistic sensitivity analyses. However, it is difficult to determine the magnitude or direction of any change. We assumed that the rates of adverse events for pregnant women and children from maternal antiviral prophylaxis were similar to those without maternal antiviral prophylaxis. Had we included complications attributable to antiviral therapy, the cost-effectiveness estimates for the strategies that included antiviral therapy would be higher (less favorable). An increasing body of evidence shows that the incidences of adverse events and birth defects among pregnant women and children associated with antiviral prophylaxis are comparable to those without antiviral prophylaxis.8,10,11,39,40,42 Our results might be conservative because we did not include the potential benefit of identifying women who should be treated or monitored for liver disease during pregnancy.
Drug resistance from long-term use of lamivudine has been a concern; however, the rate of drug resistance after a 3-month course of lamivudine is reported to be no higher than no antiviral prophylaxis.1,8,18 Tenofovir and telbivudine have low rates or no documented drug resistance when used in other settings.10,11,43 Another safety concern is postpartum flare.18,44,45 Studies report mixed results regarding change in the rate of postpartum flares after maternal antiviral prophylaxis.45,46 Because evidence for the safety of antiviral prophylaxis during pregnancy is still accumulating, antiviral prophylaxis for maternal liver disease during pregnancy has generally been postponed.16,47
Despite these limitations, our results suggest that health care providers might wish to consider HBeAg or HBV load sequential testing for HBsAg-positive pregnant women to identify women whose neonates are at increased risk for perinatal HBV infection and to ensure evaluation and monitoring of the pregnant women for the complications of chronic HBV infection, including during pregnancy and in the postpartum period.
1. Nayeri UA, Werner EF, Han CS, Pettker CM, Funai EF, Thung SF. Antenatal lamivudine to reduce perinatal hepatitis B transmission: a cost-effectiveness analysis. Am J Obstet Gynecol 2012;207:231.e1–7.
2. Smith EA, Jacques-Carroll L, Walker TY, Sirotkin B, Murphy TV. The national Perinatal Hepatitis B Prevention Program, 1994-2008. Pediatrics 2012;129:609–16.
3. Din ES, Wasley A, Jacques-Carroll L, Sirotkin B, Wang S. Estimating the number of births to hepatitis B virus-infected women in 22 states, 2006. Pediatr Infect Dis J 2011;30:575–9.
4. Margolis HS, Coleman PJ, Brown RE, Mast EE, Sheingold SH, Arevalo JA. Prevention of hepatitis-B virus transmission by immunization. An economic-analysis of current recommendations. JAMA 1995;274:1201–8.
5. Krarup H, Andersen S, Madsen PH, Christensen PB, Laursen AL, Bentzen-Petersen A, et al.; DANHEP group. HBeAg and not genotypes predicts viral load in patients with hepatitis B in Denmark: a nationwide cohort study. Scand J Gastroenterol 2011;46:1484–91.
6. Ott JJ, Stevens GA, Wiersma ST. The risk of perinatal hepatitis B virus transmission: hepatitis B e antigen (HBeAg) prevalence estimates for all world regions. BMC Infect Dis 2012;12:131.
7. Zou H, Chen Y, Duan Z, Zhang H, Pan C. Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat 2012;19:e18–25.
8. Shi ZJ, Yang YB, Ma L, Li XM, Schreiber A. Lamivudine in late pregnancy to interrupt in utero transmission of hepatitis B virus a systematic review and meta-analysis. Obstet Gynecol 2010;116:147–59.
9. Dienstag JL, Schiff ER, Wright TL, Perrillo RP, Hann HW, Goodman Z, et al.. Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med 1999;341:1256–63.
10. Pan CQ, Mi LJ, Bunchorntavakul C, Karsdon J, Huang WM, Singhvi G, et al.. Tenofovir disoproxil fumarate for prevention of vertical transmission of hepatitis B virus infection by highly viremic pregnant women: a case series. Dig Dis Sci 2012;57:2423–9.
11. Pan CQ, Han GR, Jiang HX, Zhao W, Cao MK, Wang CM, et al.. Telbivudine prevents vertical transmission from HBeAg-positive women with chronic hepatitis B. Clin Gastroenterol Hepatol 2012;10:520–6.
12. Martin JA, Hamilton BE, Ventura SJ, Osterman MJK, Wilson EC, Mathews TJ. Births: final data for 2010. Natl Vital Stat Rep 2012;61:1–72.
13. Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein ST, Wang SA, et al.; Advisory Committee on Immunization Practices (ACIP). A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep 2005;54:1–31.
14. Hoerger TJ, Schillie S, Wittenborn JS, Bradley CL, Zhou F, Byrd K, et al.. Cost-effectiveness of hepatitis B vaccination in adults with diagnosed diabetes. Diabetes Care 2013;36:63–9.
15. United States life tables, 2008. Available at: www.cdc.gov
. Retrieved December 1, 2013.
16. Nguyen G, Garcia RT, Nguyen N, Trinh H, Keeffe EB, Nguyen MH. Clinical course of hepatitis B virus infection during pregnancy. Aliment Pharmacol Ther 2009;29:755–64.
17. Kerkar N. Hepatitis B in children: complexities in management. Pediatr Transpl 2005;9:685–91.
18. Unal ER, Lazenby GB, Lintzenich AE, Simpson KN, Newman R, Goetzl L. Cost-effectiveness of maternal treatment to prevent perinatal hepatitis B virus transmission. Obstet Gynecol 2011;118:655–62.
19. Wasley A, Kruszon-Moran D, Kuhnert W, Simard EP, Finelli L, McQuillan G, et al.. The prevalence of hepatitis B virus infection in the United States in the era of vaccination. J Infect Dis 2010;202:192–201.
20. Lee CF, Gong Y, Brok J, Boxall EH, Gluud C. Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systemic review and meta-analysis. BMJ 2006;332:328–36.
21. Stevens CE, Taylor PE, Tong MJ, Toy PT, Vyas GN, Nair PV, et al.. Yeast-recombinant hepatitis-B vaccine. Efficacy with hepatitis-B immune globulin in prevention of perinatal hepatitis-B virus transmission. JAMA 1987;257:2612–6.
22. Shi ZJ, Li XM, Ma L, Yang YB. Hepatitis B immunoglobulin injection in pregnancy to interrupt hepatitis B virus mother-to-child transmission—a meta-analysis. Int J Infect Dis 2010;14:e622–34.
23. Xiao XM, Li AZ, Chen X, Zhu YK, Miao J. Prevention of vertical hepatitis B transmission by hepatitis B immunoglobulin in the third trimester of pregnancy. Int J Gynecol Obstet 2007;96:167–70.
24. Wheeley SM, Jackson PT, Boxall EH, Tarlow MJ, Gatrad AR, Anderson J, et al.. Prevention of perinatal transmission of hepatitis-B virus (HBV): a comparison 2 prophylactic schedules. J Med Virol 1991;35:212–5.
25. Wiseman E, Fraser MA, Holden S, Glass A, Kidson BL, Heron LG, et al.. Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust 2009;190:489–92.
26. Yuan J, Lin J, Xu A, Li H, Hu B, Chen J, et al.. Antepartum immunoprophylaxis of three doses of hepatitis B immunoglobulin is not effective: a single-centre randomized study. J Viral Hepat 2006;13:597–604.
27. Hung HF, Chen HH. Cost-effectiveness analysis of prophylactic lamivudine use in preventing vertical transmission of hepatitis B virus infection. Pharmacoeconomics 2011;29:1063–73.
28. Pan CQ, Duan ZP, Bhamidimarri KR, Zou HB, Liang XF, Li J, et al.. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol Hepatol 2012;10:452–9.
29. Han L, Zhang HW, Xie JX, Zhang Q, Wang HY, Cao GW. A meta-analysis of lamivudine for interruption of mother-to-child transmission of hepatitis B virus. World J Gastroenterol 2011;17:4321–33.
30. Eckman MH, Kaiser TE, Sherman KE. The cost-effectiveness of screening for chronic hepatitis B infection in the United States. Clin Infect Dis 2011;52:1294–306.
31. Hu YQ, Grau LE, Scott G, Seal KH, Marshall PA, Singer M, et al.. Economic evaluation of delivering hepatitis B vaccine to injection drug users. Am J Prev Med 2008;35:25–32.
32. Kanwal F, Farid M, Martin P, Chen G, Gralnek IM, Dulai GS, et al.. Treatment alternatives for hepatitis B cirrhosis: a cost-effectiveness analysis. Am J Gastroenterol 2006;101:2076–89.
33. Kim SY, Billah K, Lieu TA, Weinstein MC. Cost effectiveness of hepatitis B vaccination at HIV counseling and testing sites. Am J Prev Med 2006;30:498–506.
34. Post SE, Sodhi NK, Peng CH, Wan KJ, Pollack HJ. A simulation shows that early treatment of chronic hepatitis B infection can cut deaths and be cost-effective. Health Aff (Millwood) 2011;30:340–8.
35. Sawyer MH, Hoerger TJ, Murphy TV, et al.. Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP) (reprinted from MMWR, vol 60, pg 1709-1711, 2011). JAMA 2012;307:659–62.
36. Day FL, Karnon J, Rischin D. Cost-effectiveness of universal hepatitis B virus screening in patients beginning chemotherapy for solid tumors. J Clin Oncol 2011;29:3270–7.
37. Consumer price indexes—all urban consumers. Bureau of Labor Statistics, United States Department of Labor, 2011. Available at: http://www.bls.gov/cpi/home.htm
. Retrieved May 5, 2013.
38. Siegel JE, Weinstein MC, Russell LB, Gold MR. Recommendations for reporting cost-effectiveness analyses. Panel on Cost-Effectiveness in Health and Medicine. JAMA 1996;276:1339–41.
39. Buchanan C, Tran TT. Management of chronic hepatitis B in pregnancy. Clin Liver Dis 2010;14:495–504.
40. Xu WM, Cui YT, Wang L, Yang H, Liang ZQ, Li XM, et al.. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study. J Viral Hepat 2009;16:94–103.
41. Yim HJ, Lok ASF. Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology 2006;43(suppl 1):S173–81.
42. Li XM, Yang YB, Hou HY, Shi ZJ, Shen HM, Teng BQ, et al.. Interruption of HBV intrauterine transmission: a clinical study. World J Gastroenterol 2003;9:1501–3.
43. Brown RS, Verna EC, Pereira MR, Pereira MR, Tilson HH, Aguilar C, et al.. Hepatitis B virus and human immunodeficiency virus drugs in pregnancy: findings from the antiretroviral pregnancy registry. J Hepatol 2012;57:953–9.
44. Honkoop P, de Man RA, Niesters HGM, Zondervan PE, Schalm SW. Acute exacerbation of chronic hepatitis B virus infection after withdrawal of lamivudine therapy. Hepatology 2000;32:635–9.
45. ter Borg MJ, Leemans WF, de Man RA, Janssen HL. Exacerbation of chronic hepatitis B infection after delivery. J Viral Hepat 2008;15:37–41.
46. Giles ML, Visvanathan K, Lewin SR, Sasadeusz J. Chronic hepatitis B infection and pregnancy. Obstet Gynecol Surv 2012;67:37–44.
47. Keeffe EB, Dieterich DT, Han SHB, Jacobson IM, Martin P, Schiff ER, et al.. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin Gastroenterol Hepatol 2006;4:936–62.
48. Smith EA. Postvaccination serologic testing results for infants aged ≤24 months exposed to hepatitis B virus at birth—United States, 2008–2011. MMWR Morb Mortal Wkly Rep 2012;61:768–71.
49. Beasley RP, Hwang LY, Lee GCY, Lan CC, Roan CH, Huang FY, et al.. Prevention of perinatally transmitted hepatitis-B virus-infections with hepatitis-B immune globulin and hepatitis-B vaccine. Lancet 1983;2:1099–102.
50. Lee TA, Veenstra DL, Iloeje UH, Sullivan SD. Cost of chronic hepatitis B infection in the United States. J Clin Gastroenterol 2004;38(suppl 3):S144–7.
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