Authors
Dr. Laura Sauvé (biography and disclosures), Winnie Fu (biography, no disclosures), Dr. Sofia Bartlett (biography and disclosures), Dr. Orlee Guttman (biography and disclosures), Dr. Chelsea Elwood (biography, no disclosures), Dr. David Goldfarb (biography and disclosures), and Dr. Neora Pick (biography, no disclosures)
Dr. Laura Sauvé’s disclosures: No conflicts to disclose. Had received research funding from Public Health Agency Canada and Canadian Institutes of Health Research.
Dr. Sofia Bartlett’s disclosures: Has received speakers’ honoraria, consulted for, and participated in medical advisory board programs with Gilead Sciences, AbbVie, and Cepheid (no personal payments accepted), as well as investigator-initiated, unrestricted funding from Gilead Sciences and AbbVie, via the Provincial Health Services Authority and BC Centre for Disease Control Foundation for Public Health.
Dr. Orlee Guttman’s disclosures: Has received financial compensation for consulting and participating in advisory board activities for Mirum Pharmaceuticals. Mirum Pharmaceuticals is unrelated to hepatitis C virus treatment.
Dr. David Goldfarb’s disclosures: Has received investigator initiated research funding from bioMerieux Inc. He has no other relevant conflicts of interest.
Mitigating potential bias: Recommendations are consistent with published guidelines: Journal of Obstetrics and Gynaecology Canada; BC Centre for Disease Control; Canadian Pediatric Society.
What care gaps or frequently asked questions have we noticed?
The blood-borne pathogen hepatitis C virus (HCV) causes hepatitis C infection, with between 50-75% of people exposed developing chronic hepatitis C (CHC) infection. Without treatment, about 30% of those with CHC will develop liver cirrhosis within 10-30 years, which can lead to liver cancer or liver failure. CHC is also associated with increased risks of major adverse cardiovascular events, chronic kidney disease, type 2 diabetes mellitus, B-cell lymphoma, and overall mortality.1 HCV can be transmitted to infants when the pregnant person has active HCV with a detectable viral load. HCV is curable with a short course (8-12 weeks) of oral Direct Acting Antivirals (DAAs), with sustained virologic response rates of 90-100%.2
Children perinatally exposed to HCV in pregnancy have a 5-11% chance of becoming infected with HCV; many will spontaneously clear the virus before 2 years of age. However, those who do not are at risk of having the complications of CHC occurring in early adulthood despite being asymptomatic in childhood. Testing for perinatally acquired HCV can involve either HCV RNA at 3-6 months of age, or HCV serology at 18 months of age. Currently, the BC Centre for Disease Control (BCCDC)3 recommends that perinatally HCV-exposed infants have HCV serology alone performed at 18 months to avoid recurrent testing in those who spontaneously clear the virus.
Given the concern for loss to follow-up for many HCV-exposed infants,4 earlier HCV RNA testing can be offered for children in families experiencing barriers to care.
In BC, primary care providers and pediatricians who are caring for HCV-exposed infants should order HCV testing. However, many HCV-exposed infants in BC are not tested. Infants and children who are tested and identified with CHC are referred to and managed through the BC Children’s Hospital (BCCH) Gastroenterology Clinic by pediatric gastroenterologists, where they ideally have regular monitoring and DAA treatment after age 3 if indicated (DAA treatment is approved for children 3 years of age and older in Canada).
Data that answer these questions or gaps
Approximately 0.5% of pregnant people in BC have HCV; based on estimates of 42,000 live annual births in BC, vertical transmission rates of 5-11%, and estimating that 80% of vertically infected children develop CHC, there could be anywhere between 8-18 new cases of CHC from vertical transmission each year in BC. However, there are only about 2-3 new case referrals to the BCCH Gastroenterology clinic annually. Additionally, BCCDC receives an average of 2 HCV case reports each year among pediatric patients that meet the chronic HCV case definition.
Follow-up rates in North America for infants exposed to HCV perinatally have been low at less than 30%. For opioid-exposed infants, follow-up has been observed to be as low as 10%, suggesting that populations with existing barriers may be further disadvantaged.5
Taken together, this suggests that a high proportion of infants exposed to HCV may be lost to care in the current system in BC.
However, the literature indicates that implementing clear algorithms for infant testing, education to primary care providers, and reminders for pediatricians, as well as wraparound services and integrated care, can significantly improve linkage to care and connect families with the appropriate resources.6-9
Obstetrical societies are increasingly suggesting that HCV screening be included in routine prenatal screening. While BC continues to follow risk-based screening, prenatal screening for HCV in the province has increased over the years, while new diagnoses have remained stable, suggesting that low or no-risk individuals are being screened.10
What we recommend
People of reproductive age who have chronic HCV infection should be counselled on the importance of treatment prior to becoming pregnant, as there are insufficient data on treatment in pregnancy currently.
Care providers looking after pregnant people should:
- Establish if the pregnant person has a known history of HCV infection. If so, a viral load should be sent if a viral load has not been performed in the past or if there are ongoing risks of re-acquisition, regardless of treatment status. If there is no known history, providers should have a low threshold for HCV screening.3
- If there is indication of active infection (HCV RNA positive):
- Provide counseling on the risk of perinatal acquisition (~5%) and the need for follow-up testing. There is no impact of HCV on risk of preterm birth, pre-eclampsia, or other complications in pregnancy. Pregnant persons can largely be reassured but encouraged to seek treatment after delivery.
Ensure that the partner is tested for HCV as well. - If the provider does not provide DAA treatment, offer referral to a provider that does either immediately, or after the pregnancy.11 There is a lack of safety data for DAA treatment in pregnancy currently.
- There is no indication to change the mode of delivery and breastfeeding continues to be recommended for HCV in pregnancy. Providers should however avoid the use of scalp electrodes and operative vaginal delivery where possible.
- Ensure the HCV RNA positive status of the mother is communicated to the pediatrician/health care provider caring for their infant.
- Provide counseling on the risk of perinatal acquisition (~5%) and the need for follow-up testing. There is no impact of HCV on risk of preterm birth, pre-eclampsia, or other complications in pregnancy. Pregnant persons can largely be reassured but encouraged to seek treatment after delivery.
Pediatricians and primary care providers looking after infants exposed to HCV should:
- Ensure that the caregiver is aware of the recommendations for HCV testing in infants.
- For all HCV-exposed infants, ensure testing is complete:
- Add HCV exposure to the infant’s electronic health record (EHR) as a problem to be followed.
- If there are barriers to follow-up, create a reminder for testing at 3-4 months of age for HCV PCR testing. If not, as per the most recent Canadian Paediatric Society Guidelines,4 schedule serology testing at 12-18 months of age.
- For infants with positive HCV RNA prior to 12 months of age, repeat the test after 12 months of age to confirm the result, along with liver enzymes. If a second test is confirmed to be positive:
- Refer to BCCH Gastroenterology.12
- Consider whether referral to a general pediatrician is needed in the context of adverse childhood experiences, perinatal substance exposure and presence of developmental delay – this population may experience barriers to care and may benefit from ongoing general pediatrics care where possible.
- Consider testing other siblings in the family.
Pediatricians or primary care providers looking after children or youth (18 months of age or older) who have evidence of HCV exposure during infancy with unknown or incomplete follow-up should:
- Order HCV serology if not previously performed. If it is positive, order HCV RNA.
- If HCV RNA testing is positive, please refer to BCCH Gastroenterology and if needed, a general pediatrician for ongoing general pediatrics care.
- Consider recommending peer support through YouthCo for those who are 6-19 years of age (www.youthco.org)
Handout
View and download the handout that you can provide to patients. Download PDF.
Resources
- Bitnun A. Position statement: the management of infants, children, and youth at risk for hepatitis C virus (HCV) infection. Canadian Pediatric Society. Nov 5, 2021. Accessed December 14, 2023. (View)
- Boucher M, Gruslin A. No. 96-The reproductive care of women living with hepatitis C infection. Journal of Obstetrics and Gynaecology Canada. 2017;39(7):e1-e25. doi:10.1016/j.jogc.2017.04.007. (View)
- Communicable disease control hepatitis C. BC Centre for Disease Control. April 2021. Accessed December 14, 2023. (View)
- Gastroenterology referral. BC Children’s Hospital. Accessed December 10, 2023. (View)
References
- Cacoub P, Saadoun D. Extrahepatic manifestations of chronic HCV infection. N Engl J Med. 2021;384(11):1038-1052. doi:10.1056/NEJMra2033539 (View with UBC)
- Manns MP, Buti M, Gane E, et al. Hepatitis C virus infection. Nat Rev Dis Primers. 2017;3:17006. Published 2017 Mar 2. doi:10.1038/nrdp.2017.6 (View with UBC)
- Communicable disease control hepatitis C. BC Centre of Disease Control. April 2021. Accessed December 11, 2023. (View)
- The management of infants, children, and youth at risk for hepatitis C virus (HCV) infection. Canadian Paediatric Society. Updated November 5, 2021. Accessed December 11, 2023. (View)
- Protopapas S, Murrison LB, Wexelblatt SL, Blackard JT, Hall ES. Addressing the disease burden of vertically acquired hepatitis C virus infection among opioid-exposed infants. Open Forum Infect Dis. 2019;6(12):ofz448. Published 2019 Oct 21. doi:10.1093/ofid/ofz448 (View)
- Hojat LS, Greco PJ, Bhardwaj A, Bar-Shain D, Abughali N. Using preventive health alerts in the electronic health record improves hepatitis C virus testing among infants perinatally exposed to hepatitis C. Pediatr Infect Dis J. 2020;39(10):920-924. doi:10.1097/INF.0000000000002757 (View with UBC)
- Abughali N, Maxwell JR, Kamath AS, Nwankwo U, Mhanna MJ. Interventions using electronic medical records improve follow up of infants born to hepatitis C virus infected mothers. Pediatr Infect Dis J. 2014;33(4):376-380. doi:10.1097/INF.0000000000000129 (View with UBC)
- Crook TW, Munn EK, Scott TA, et al. Improving the discharge process for opioid-exposed neonates. Hosp Pediatr. 2019;9(8):643-648. doi:10.1542/hpeds.2019-0088. (View)
- Epstein RL, Moloney C, Garfinkel J, et al. Enhancing linkage to hepatitis C virus treatment following pregnancy in women identified during perinatal care. Hepatol Commun. 2021;5(9):1543-1554. doi:10.1002/hep4.1748 (View)
- Pearce ME, Yu A, Alvarez M, et al. Prenatal hepatitis C screening, diagnoses, and follow-up testing in British Columbia, 2008-2019. PLoS One. 2020;15(12):e0244575. Published 2020 Dec 31. doi:10.1371/journal.pone.0244575 (View)
- Hepatitis C treatment guide. BC Centre for Disease Control Provincial Health Services Authority. April, 2021. Accessed December 13, 2023. (View)
- Gastroenterology referral. BC Children’s Hospital. Accessed December 10, 2023. (View)
Vote
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Data would be available from BCCDC on the propotion who are actually not followed up. In the absence of this information, this article is potentially misleading and inappropriate. It may well be valid, but the arguement “just because we think so many children are lost to follow up” is not evidenced based medicine.
I will consider changing my practice, but need more information/time
Great article! Our current data here in Alberta shows that only ~30% of perinatally HCV-exposed infants are being followed up and of those who are, about half are being tested for HCV antibodies before 18 months (with many of those testing antibody positive being LTFU afterwards, so their status remains unknown). Efficient post-partum linkage to care programs and effective health information transfer to pediatricians/primary care providers will be crucial to ensure follow-up in infants, especially if testing is deferred until 12-18 months.
Response to Paul Hassleback:
Thank you for your comment. Unfortunately at this time, in BC we (BCCDC / BC Children’s and Women’s Hospitals / Perinatal Services BC) do not have the linked maternal and infant data to determine what proportion of infants born to mothers with hepatitis C are not followed up – we are actually working on just such a study as it is an important question.
In the meantime, there are a large number of studies from other jurisdictions that suggest that follow up rates for infants perinatally exposed to hepatitis C are 25-50%; and our clinical experience in BC suggests that the proportion is similar (if not worse) in BC. The gaps in testing have led to a change in public health guidelines in the United States, moving to universal testing of all exposed infants at 2-6 months (see US CDC recommendations); current Canadian guidelines continue to preferentially recommend serology at 18 months with PCR used at 2-6 months for those where loss to follow up is anticipated (see BCCDC Guidelines, and the Canadian Pediatric Society Guidelines)
While the This Changed My Practice review did not include the exhaustive evidence list, we did in fact do an exhaustive review in preparing this article; a sampling of studies of rates of follow up include:
1. In Australia, Reid and colleagues found that 10% of their cohort had appropriate follow up (Reid S, Day CA, Bowen DG, et al. Vertical transmission of hepatitis C: Testing and health-care engagement. J Paediatrics and Child Health. 2018;54(6):647-652. doi:10.1111/jpc.13832).
2. In New Brunswick, Gander and colleagues identified that approximately 25% of their cohort had appropriate testing done (Gander S, Morris A, Materniak S. An Evaluation of Hepatitis C Screening in Infants and Children Born to Seropositive Mothers in Saint John, New Brunswick. Cureus. 2021;13(8):e17377. Published 2021 Aug 23. doi:10.7759/cureus.17377 – View)
3. In Tennessee, Lopata and colleagues found that 25% had been tested (Lopata SM, McNeer E, Dudley JA, et al. Hepatitis C Testing Among Perinatally Exposed Infants. Pediatrics. 2020;145(3):e20192482. doi:10.1542/peds.2019-2482 – View)