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Testing for Hepatitis C in Pregnancy: the Time Has Come for Routine Rather than Risk-Based

  • Hepatitis C (H Vargas and S Flamm, Section Editors)
  • Published:
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Abstract

Purpose of Review

The purpose of this review is to discuss the reasons for HCV testing during pregnancy and to review what is known about antiviral treatment during pregnancy.

Recent Findings

Hepatitis C virus affects over 3 million persons in the USA and is one of the leading infectious causes of death. While HCV is most commonly transmitted via parenteral exposures, thus affecting people who inject drugs, it is also transmitted from mother-to-child. Due to an expanding opioid crisis, an increasing number of women of childbearing age are now infected, resulting in transmission to infants. Risk-based screening has never been proven effective and thus universal screening of pregnant women for HCV infection has been recommended.

Summary

Obstetricians may play a key role in the USA by implementing universal testing for HCV in pregnant women, thereby enhancing the health of mothers and identifying children at risk.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Grebely J, Page K, Sacks-Davis R, van der Loeff MS, Rice TM, Bruneau J, et al. The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection. Hepatology. 2014;59(1):109–20. https://doi.org/10.1002/hep.26639.

    Article  CAS  PubMed  Google Scholar 

  2. Hallager S, Brehm Christensen P, Ladelund S, Rye Clausen M, Lund Laursen A, Moller A, et al. Mortality rates in patients with chronic hepatitis C and cirrhosis compared with the general population: a Danish cohort study. J Infect Dis. 2017;215(2):192–201. https://doi.org/10.1093/infdis/jiw527.

    Article  CAS  PubMed  Google Scholar 

  3. Ly KN, Hughes EM, Jiles RB, Holmberg SD. Rising mortality associated with hepatitis C virus in the United States, 2003-2013. Clin Infect Dis. 2016;62(10):1287–8. https://doi.org/10.1093/cid/ciw111.

    Article  PubMed  Google Scholar 

  4. Suryaprasad AG, White JZ, Xu F, Eichler BA, Hamilton J, Patel A, et al. Emerging epidemic of hepatitis C virus infections among young nonurban persons who inject drugs in the United States, 2006-2012. Clin Infect Dis. 2014;59(10):1411–9. https://doi.org/10.1093/cid/ciu643.

    Article  CAS  PubMed  Google Scholar 

  5. •• Ly KN, Jiles RB, Teshale EH, Foster MA, Pesano RL, Holmberg SD. Virus infection among reproductive-aged women and children in the United States, 2006 to 2014. Ann Intern Med. 2017;166(11):775–82. https://doi.org/10.7326/M16-2350 Important CDC study indicating an alarming increase in young women with HCV and therefore infants at risk for transmission.

    Article  PubMed  Google Scholar 

  6. • AASLD-IDSA HCV Guidance Panel. Hepatitis C Guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. 2018;67(10):1477–92. https://doi.org/10.1093/cid/ciy585 Important consensus guidelines by two major specialty societies providing immediate guidance for clinicians regarding the testing, management, and care for those living with HCV.

    Article  CAS  Google Scholar 

  7. Society for Maternal-Fetal Medicine, Hughes BL, Page CM, Kuller JA. Hepatitis C in pregnancy: screening, treatment, and management. Am J Obstet Gynecol. 2017;217(5):B2–B12. https://doi.org/10.1016/j.ajog.2017.07.039.

    Article  Google Scholar 

  8. Centers for Disease C, Prevention. Hepatitis C virus infection among adolescents and young adults: Massachusetts, 2002–2009. MMWR Morb Mortal Wkly Rep. 2011;60(17):537–41.

    Google Scholar 

  9. Rosenberg ES, Rosenthal EM, Hall EW, Barker L, Hofmeister MG, Sullivan PS, et al. Prevalence of hepatitis C virus infection in US states and the District of Columbia, 2013 to 2016. JAMA Netw Open. 2018;1(8):e186371. https://doi.org/10.1001/jamanetworkopen.2018.6371.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Salemi JL, Spooner KK, Mejia de Grubb MC, Aggarwal A, Matas JL, Salihu HM. National trends of hepatitis B and C during pregnancy across sociodemographic, behavioral, and clinical factors, United States, 1998-2011. J Med Virol. 2017;89(6):1025–32. https://doi.org/10.1002/jmv.24725.

    Article  PubMed  Google Scholar 

  11. Centers for Disease C, Prevention. Notes from the field: hepatitis C virus infections among young adults--rural Wisconsin, 2010. MMWR Morb Mortal Wkly Rep. 2012;61(19):358.

    Google Scholar 

  12. Cicero TJ, Ellis MS, Surratt HL, Kurtz SP. The changing face of heroin use in the United States: a retrospective analysis of the past 50 years. JAMA Psychiatry. 2014;71(7):821–6. https://doi.org/10.1001/jamapsychiatry.2014.366.

    Article  PubMed  Google Scholar 

  13. Zibbell JE, Iqbal K, Patel RC, Suryaprasad A, Sanders KJ, Moore-Moravian L, et al. Increases in hepatitis C virus infection related to injection drug use among persons aged </=30 years - Kentucky, Tennessee, Virginia, and West Virginia, 2006-2012. MMWR Morb Mortal Wkly Rep. 2015;64(17):453–8.

    PubMed  PubMed Central  Google Scholar 

  14. Esmaeili A, Mirzazadeh A, Carter GM, Esmaeili A, Hajarizadeh B, Sacks HS, et al. Higher incidence of HCV in females compared to males who inject drugs: a systematic review and meta-analysis. J Viral Hepat. 2017;24(2):117–27. https://doi.org/10.1111/jvh.12628.

    Article  CAS  PubMed  Google Scholar 

  15. • Esmaeili A, Mirzazadeh A, Morris MD, Hajarizadeh B, Sacks HS, Maher L, et al. The effect of female sex on hepatitis C incidence among people who inject drugs: results from the International Multicohort InC3 Collaborative. Clin Infect Dis. 2018;66(1):20–8. https://doi.org/10.1093/cid/cix768 An analysis of various cohorts across continents indicating that females who inject drugs may be at higher risk than males to be infected with HCV.

    Article  CAS  PubMed  Google Scholar 

  16. Marsh JC, Park K, Lin YA, Bersamira C. Gender differences in trends for heroin use and nonmedical prescription opioid use, 2007-2014. J Subst Abus Treat. 2018;87:79–85. https://doi.org/10.1016/j.jsat.2018.01.001.

    Article  Google Scholar 

  17. • Watts T, Stockman L, Martin J, Guilfoyle S, Vergeront JM. Increased risk for mother-to-infant transmission of hepatitis C virus among Medicaid recipients - Wisconsin, 2011-2015. MMWR Morb Mortal Wkly Rep. 2017;66(42):1136–9. https://doi.org/10.15585/mmwr.mm6642a3 CDC report indicating increasing risk for perinatal transmission of HCV.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Rossi RM, Warshak CR. Prevalence of maternal hepatitis C virus infection in Ohio. Obstet Gynecol. 2018;132(3):708–16. https://doi.org/10.1097/AOG.0000000000002807.

    Article  PubMed  Google Scholar 

  19. Patrick SW, Bauer AM, Warren MD, Jones TF, Wester C. Hepatitis C virus infection among women giving birth - Tennessee and United States, 2009-2014. MMWR Morb Mortal Wkly Rep. 2017;66(18):470–3. https://doi.org/10.15585/mmwr.mm6618a3.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Espinosa CM, Jhaveri R. Update on the management of hepatitis B and C infections in the neonatal period. Semin Perinatol. 2018;42(3):185–90. https://doi.org/10.1053/j.semperi.2018.02.006.

    Article  PubMed  Google Scholar 

  21. Modin L, Arshad A, Wilkes B, Benselin J, Lloyd C, Irving WL, et al. Epidemiology and natural history of hepatitis C virus infection among children and young people. J Hepatol. 2018;70:371–8. https://doi.org/10.1016/j.jhep.2018.11.013.

    Article  PubMed  Google Scholar 

  22. Delgado-Borrego A, Smith L, Jonas MM, Hall CA, Negre B, Jordan SH, et al. Expected and actual case ascertainment and treatment rates for children infected with hepatitis C in Florida and the United States: epidemiologic evidence from statewide and nationwide surveys. J Pediatr. 2012;161(5):915–21. https://doi.org/10.1016/j.jpeds.2012.05.002.

    Article  PubMed  Google Scholar 

  23. •• Kuncio DE, Newbern EC, Johnson CC, Viner KM. Failure to test and identify perinatally infected children born to hepatitis C virus-infected women. Clin Infect Dis. 2016;62(8):980–5. https://doi.org/10.1093/cid/ciw026 An important study documenting the inability to identify pregnant women with HCV via risk factor–based screening.

    Article  PubMed  Google Scholar 

  24. Chappell CA, Hillier SL, Crowe D, Meyn LA, Bogen DL, Krans EE. Hepatitis C virus screening among children exposed during pregnancy. Pediatrics. 2018;141(6). doi:https://doi.org/10.1542/peds.2017-3273.

  25. Wiese M, Grungreiff K, Guthoff W, Lafrenz M, Oesen U, Porst H. Outcome in a hepatitis C (genotype 1b) single source outbreak in Germany--a 25-year multicenter study. J Hepatol. 2005;43(4):590–8.

    Article  PubMed  Google Scholar 

  26. Di Martino V, Lebray P, Myers RP, Pannier E, Paradis V, Charlotte F, et al. Progression of liver fibrosis in women infected with hepatitis C: long-term benefit of estrogen exposure. Hepatology. 2004;40(6):1426–33. https://doi.org/10.1002/hep.20463.

    Article  CAS  PubMed  Google Scholar 

  27. Sarkar M, Dodge JL, Greenblatt RM, Kuniholm MH, DeHovitz J, Plankey M, et al. Reproductive aging and hepatic fibrosis progression in human immunodeficiency virus/hepatitis C virus-coinfected women. Clin Infect Dis. 2017;65(10):1695–702. https://doi.org/10.1093/cid/cix643.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pergam SA, Wang CC, Gardella CM, Sandison TG, Phipps WT, Hawes SE. Pregnancy complications associated with hepatitis C: data from a 2003–2005 Washington state birth cohort. Am J Obstet Gynecol. 2008;199(1):38 e1–9. https://doi.org/10.1016/j.ajog.2008.03.052.

    Article  Google Scholar 

  29. Huang QT, Hang LL, Zhong M, Gao YF, Luo ML, Yu YH. Maternal HCV infection is associated with intrauterine fetal growth disturbance: a meta-analysis of observational studies. Medicine (Baltimore). 2016;95(35):e4777. https://doi.org/10.1097/MD.0000000000004777.

    Article  Google Scholar 

  30. Wijarnpreecha K, Thongprayoon C, Sanguankeo A, Upala S, Ungprasert P, Cheungpasitporn W. Hepatitis C infection and intrahepatic cholestasis of pregnancy: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2017;41(1):39–45. https://doi.org/10.1016/j.clinre.2016.07.004.

    Article  PubMed  Google Scholar 

  31. Conte D, Fraquelli M, Prati D, Colucci A, Minola E. Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women. Hepatology. 2000;31(3):751–5. https://doi.org/10.1002/hep.510310328.

    Article  CAS  PubMed  Google Scholar 

  32. Honegger JR, Kim S, Price AA, Kohout JA, McKnight KL, Prasad MR, et al. Loss of immune escape mutations during persistent HCV infection in pregnancy enhances replication of vertically transmitted viruses. Nat Med. 2013;19(11):1529–33. https://doi.org/10.1038/nm.3351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hashem M, Jhaveri R, Saleh DA, Sharaf SA, El-Mougy F, Abdelsalam L, et al. Spontaneous viral load decline and subsequent clearance of chronic hepatitis C virus in postpartum women correlates with favorable interleukin-28B gene allele. Clin Infect Dis. 2017;65(6):999–1005. https://doi.org/10.1093/cid/cix445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Food and Drug Administration. Harvoni Package Insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205834s001lbl.pdf. Accessed January 28, 2019. 2015.

  35. Food and Drug Administration. Epclusa Package Insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208341s000lbl.pdf. Accessed: January 15, 2019.

  36. Food and Drug Administration. Daklinza Package Insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206843s006lbl.pdf. Accessed January 28, 2019. .

  37. Food and Drug Administration. Mavyret Package Insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf. Accessed: February 8, 2018.

  38. Kushner T, Cohen J, Tien PC, Terrault NA. Evaluating women’s preferences for hepatitis C treatment during pregnancy. Hepatol Commun. 2018;2(11):1306–10. https://doi.org/10.1002/hep4.1264.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Gilbert EM, Darin KM, Scarsi KK, McLaughlin MM. Antiretroviral pharmacokinetics in pregnant women. Pharmacotherapy. 2015;35(9):838–55. https://doi.org/10.1002/phar.1626.

    Article  PubMed  Google Scholar 

  40. United States Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research. Guidance for industry: pharmacokinetics in pregnancy - study design, data analysis, and impact on dosing and labeling. October 2004. https://www.fda.gov/downloads/Drugs/.../Guidances/ucm072133.pdf. Accessed on February 8, 2018.

  41. US National Institutes of Health, US National Library of Medicine. Study of hepatitis C treatment during pregnancy. Available at: https://clinicaltrials.gov/ct2/show/NCT02683005. Accessed January 29, 2019.

  42. •• Chappell CA, Krans EE, Bunge K, Macio I, Bogen D, Scarsi KK et al., editors. A phase one study of ledipasvir/sofosbuvir in pregnant women with hepatitis C virus. Abstract #87 Conference on Retroviruses and Opportunistic Infections, Seattle, Washington, 2019. 2019; Seattle, Washington. First study showing initial safety and outcomes of DAA treatment in 8 pregnant women.

  43. Robaeys G, Bielen R, Azar DG, Razavi H, Nevens F. Global genotype distribution of hepatitis C viral infection among people who inject drugs. J Hepatol. 2016;65(6):1094–103. https://doi.org/10.1016/j.jhep.2016.07.042.

    Article  PubMed  Google Scholar 

  44. Coyle C, Kwakwa H, Viner K. Integrating routine HCV testing in primary care: lessons learned from five federally qualified health centers in Philadelphia, Pennsylvania, 2012-2014. Public Health Rep. 2016;131(Suppl 2):65–73. https://doi.org/10.1177/00333549161310S211.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Centers for Disease C. Prevention of perinatal transmission of hepatitis B virus: prenatal screening of all pregnant women for hepatitis B surface antigen. MMWR Morb Mortal Wkly Rep. 1988;37(22):341–6 51.

    Google Scholar 

  46. Alberti A, Noventa F, Benvegnu L, Boccato S, Gatta A. Prevalence of liver disease in a population of asymptomatic persons with hepatitis C virus infection. Ann Intern Med. 2002;137(12):961–4.

    Article  PubMed  Google Scholar 

  47. • Fernandez N, Towers CV, Wolfe L, Hennessy MD, Weitz B, Porter S. Sharing of snorting straws and hepatitis C virus infection in pregnant women. Obstet Gynecol. 2016;128(2):234–7. https://doi.org/10.1097/AOG.0000000000001507 Study from Kentucky with finding that snorting drugs may be an important risk factor for acquiring HCV among women.

    Article  PubMed  Google Scholar 

  48. Boudova S, Mark K, El-Kamary SS. Risk-Based Hepatitis C Screening in pregnancy is less reliable than universal screening: a retrospective chart review. Open Forum Infect Dis. 2018;5(3):ofy043. https://doi.org/10.1093/ofid/ofy043.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Kuncio DE, Newbern EC, Fernandez-Vina MH, Herdman B, Johnson CC, Viner KM. Comparison of risk-based hepatitis C screening and the true seroprevalence in an urban prison system. J Urban Health. 2015;92(2):379–86. https://doi.org/10.1007/s11524-015-9945-4.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Roblin DW, Smith BD, Weinbaum CM, Sabin ME. HCV screening practices and prevalence in an MCO, 2000-2007. Am J Manag Care. 2011;17(8):548–55.

    PubMed  Google Scholar 

  51. Page K, Leeman L, Bishop S, Cano S, Bakhireva LN. Hepatitis C cascade of care among pregnant women on opioid agonist pharmacotherapy attending a comprehensive prenatal program. Matern Child Health J. 2017;21(9):1778–83. https://doi.org/10.1007/s10995-017-2316-x.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Chasnoff IJ, Landress HJ, Barrett ME. The prevalence of illicit-drug or alcohol use during pregnancy and discrepancies in mandatory reporting in Pinellas County, Florida. N Engl J Med. 1990;322(17):1202–6. https://doi.org/10.1056/NEJM199004263221706.

    Article  CAS  PubMed  Google Scholar 

  53. Garg M, Garrison L, Leeman L, Hamidovic A, Borrego M, Rayburn WF, et al. Validity of self-reported drug use information among pregnant women. Matern Child Health J. 2016;20(1):41–7. https://doi.org/10.1007/s10995-015-1799-6.

    Article  PubMed  PubMed Central  Google Scholar 

  54. • Waruingi W, Mhanna MJ, Kumar D, Abughali N. Hepatitis C Virus universal screening versus risk based selective screening during pregnancy. J Neonatal Perinatal Med. 2015;8(4):371–8. https://doi.org/10.3233/NPM-15915024 A study indicating that risk-based screening is ineffective.

    Article  CAS  PubMed  Google Scholar 

  55. •• Rose M, Myers J, Evans J, Prince A, Espinosa C, editors. Abstract 87: hepatitis C risk-based vs. universal screening among pregnant women: implementation and cost-effectiveness analysis. The Liver Meeting; 2018 November 11; San Francisco, CA. Demonstration project indicating 20-fold increase in identifying pregnant women by implementation of universal screening for HCV; also indicates cost-effectiveness.

  56. Krans EE, Rothenberger SD, Morrison PK, Park SY, Klocke LC, Turocy MJ, et al. Hepatitis C virus knowledge among pregnant women with opioid use disorder. Matern Child Health J. 2018;22(8):1208–16. https://doi.org/10.1007/s10995-018-2506-1.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Boaz K, Fiore AE, Schrag SJ, Gonik B, Schulkin J. Screening and counseling practices reported by obstetrician-gynecologists for patients with hepatitis C virus infection. Infect Dis Obstet Gynecol. 2003;11(1):39–44. https://doi.org/10.1155/S106474490300005X.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Giles ML, Garland SM, Grover SR, Lewin SM, Hellard ME. Impact of an education campaign on management in pregnancy of women infected with a blood-borne virus. Med J Aust. 2006;184(8):389–92.

    PubMed  Google Scholar 

  59. National Viral Hepatitis Roundtable and Center for Health Law & Policy Innovation. Hepatitis C: the state of Medicaid access. 2017 national summary report. Available at: https://stateofhepc.org/about/.

  60. • Tasillo A, Eftekhari Yazdi G, Nolen S, Schillie S, Vellozzi C, Epstein R, et al. Short-term effects and long-term cost-effectiveness of universal hepatitis C testing in prenatal care. Obstet Gynecol. 2019. https://doi.org/10.1097/AOG.0000000000003062 Modeling study indicating that universal screening would capture more cases of HCV and that this approach would be cost-effective compared with current standards of risk factor–based screening.

  61. • 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 (Accepted, in press). 2019. Another modeling study which also indicates the cost-effectiveness of universal screening of HCV; indicates that this approach would be even more cost-effective if more infants were properly tested.

  62. Arora S, Thornton K, Murata G, Deming P, Kalishman S, Dion D, et al. Outcomes of treatment for hepatitis C virus infection by primary care providers. N Engl J Med. 2011;364(23):2199–207. https://doi.org/10.1056/NEJMoa1009370.

    Article  CAS  PubMed  Google Scholar 

  63. Barua S, Greenwald R, Grebely J, Dore GJ, Swan T, Taylor LE. Restrictions for Medicaid reimbursement of sofosbuvir for the treatment of hepatitis C virus infection in the United States. Ann Intern Med. 2015;163(3):215–23. https://doi.org/10.7326/M15-0406.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, Box 1123, One Gustave L Levy Place, New York, NY, 10029, USA

    Tatyana Kushner

  2. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, 300 Halket Street, Pittsburgh, PA, 15213, USA

    Catherine A. Chappell

  3. Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street Cox 6, Boston, MA, 02114, USA

    Arthur Y. Kim

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Correspondence to Arthur Y. Kim.

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Conflict of Interest

Catherine A. Chappell has received research funding from Gilead Sciences and Merck though Magee-Womens Research Institute (MWRI) and has served as a consultant for Gilead Sciences. Arthur Y. Kim served as a consultant for Biomarin, Inc. Tatyana Kushner reports personal fees from Gilead Sciences for participation in a scientific advisory board, outside the submitted work.

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Kushner, T., Chappell, C.A. & Kim, A.Y. Testing for Hepatitis C in Pregnancy: the Time Has Come for Routine Rather than Risk-Based. Curr Hepatology Rep 18, 206–215 (2019). https://doi.org/10.1007/s11901-019-00468-y

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