1. Prevention of Perinatal HBV and HCV Transmission
John W. Ward, M.D.
Director, Division of Viral Hepatitis
Centers for Disease Control and Prevention
Division of Viral Hepatitis
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

2. Natural History of HBV Infection
Varies depending on age of infection
Among infected children acute (symptomatic) hepatitis B rare; likelihood of developing chronic infection high:
Age at infection
<1 year
1-5 years
>5 years
Acute HBV
<1%
5-15%
20-50%
Chronic HBV
90%
25-50%
6-10%
Figuring out disease burden also depends on the natural history of HBV infection which is very dependent on age of infection.
Among children who become HBV infected, acute symptomatic hepatitis B is rare, occurring in <1% of infants and only 5-15% of children 1 to 5 years old.
However, the likelihood of progression to chronic infection - which accounts for most HBV-related morbidity and mortality - is highest in these age groups - developing in 90% of infants and 25-50% of young children.
Because the consequences of chronic infection - cirrhosis and hepatocellular carcinoma or HCC - are not usually apparent until adulthood - infection among children goes unrecognized.
Clearly, preventing HBV infection in the perinatal and early childhood periods should have a major impact on reducing chronic HBV disease.
Morbidity and mortality associated with chronic infection > 90% of deaths from cirrhosis and hepatocellular carcinoma

4. Current Recommendations to Eliminate HBV Transmission among Vaccinated Pediatric Cohorts United States
Universal Birth dose of Hepatitis B vaccine- 70% coverage
Timely completion hepatitis B vaccine series -93% coverage
Maternal HBsAg testing - >90%
Infants of HBsAg+ mothers
HepB vaccine /HBIG < 12 hours of birth
Post-vaccination serology* (HBsAg and anti-HBs)
~1 % of infants become HBsAg+
10.
To prevent perinatal hepatitis B transmission, infants born to HBsAg-positive pregnant women receive post-exposure prophylaxis consisting of …..
Hepatitis B vaccine and hepatitis B immune globulin, or HBIG, administered within 12 hours of birth,
Timely completion of a hepatitis B vaccine series, and
Post-vaccination testing at 9 months of age, 1-2 months after the final vaccine dose; testing includes both HBsAg for infection, and antibody to HBsAg, for immunity to infection.
Infants who are not immune (but not infected) are revaccinated with another hepatitis B vaccine series, and retested. NEXT SLIDE
CDC, MMWR 2012, 2013

5. Infants of HBsAg-positive women, 1984
Hepatitis B Vaccine Policy and Rates of Acute Hepatitis B, U.S.,
Universal maternal HBsAg testing 1988
Infants of HBsAg-positive women, 1984
High-risk groups,*1982
*Health care providers, MSM, IDU, hemodialysis patients, household & sexual partners of persons with chronic HBV, persons in certain institutional settings, e.g, inmates of long-term correctional facilities.
Source: National Notifiable Disease Surveillance System (NNDSS)

6. HepB Vaccination Has Decreased HBV incidence Protecting Newborns Remains a Challenge
HCV incidence

7. Outcomes of Infants Born to HBsAg+ Women – United States 2008-2013
95%
96% 1%
17, 951 mother –infant pairs; 11,,335 with data for HBIG/HepB status;
100 HBsAg+ infants
S Schillie, Pediatrics 2015

8. Interventions to Improve Prevention of Perinatal HBV Transmission
Case management of HBV exposed infants
Maternal HBV testing- USPSTF recommendation
Hepatitis B Perinatal Prevention Coordinators- manage ~50% of exposed infants
Addition of pregnancy status to HBV test requisitions
Medicaid support for case management (discussed with CMS)
Birth dose
CDC recommendation – for vaccination before hospital discharge
Standing orders
Evaluation criteria for licensing of birth facilities

9. Results of Perinatal Prophylaxis to Prevent Vertical Transmission of HBV
3353 HBV exposed infants received HBIG, HepB vaccine < 12 hrs of birth
99% of infants protected from HBV infection
25 infants (0.75%) became HBV infected; 0.75/100 births
24/25 born to HBeAg+ mothers; (RR 79.92)
All transmissions at maternal HBV DNA > 5 × 107 IU/mL
Kubo A et al. Ann Intern Med Jun 17;160(12):828-35

10. Cost-Effectiveness : HBeAg or HBV DNA Testing
vs. Current Recommendation
Variable
Range
ICER
($/QALY saved)
Sequential HBeAg test
Sequential HBV
DNA load test
Decrease in perinatal transmission with antiviral treatment
20% - 80% reduction
Cost saving – 4,708
Cost saving – 11,167
L, Fan, Obstet Gynecol May

11. Updating ACIP Recommendations for Hepatitis B Vaccination
Advisory Committee for Immunization Practices ACIP
October 2016

12. Updates to ACIP Statement
Hepatitis B vaccine birth dose administered within 24 hours of birth for medically stable infants weighing ≥2,000 grams and born to HBsAg-negative mothers
Testing HBsAg-positive pregnant women for hepatitis B virus (HBV) DNA to guide the use of maternal antiviral therapy during pregnancy for prevention of perinatal HBV transmission
Refer to AASLD recommendation for the use of antiviral therapy among mothers with HBV DNA >200,000 IU/mL for preventing perinatal transmission
Post-vaccination serologic testing for infants whose mother’s HBsAg status remains unknown indefinitely
Recommend hepatitis B vaccination for persons with HCV and for those with chronic liver disease

13. Modes of HCV Transmission
Unsafe health care – Most common risk globally
Injection drug use- population with highest HCV prevalence
Other modes
Perinatal
Sexual transmission; rare; HIV infected MSM at highest risk
Also reported - (e,g inhaled drugs , unregulated tattooing, household)
Over the past several years, awareness of the global burden of disease associated with unsafe injections, especially those given in the healthcare settings, has increased. Recently published models suggest that, annually, more than 20 million new HBV infections, more than 2 million new HCV infections, and more than 250,000 new HIV infections are associated with unsafe injections.
Prevention measures have reduced not eliminated transmission risk
MMWR Recommendations and Reports June 29, 2001 / 50(RR11);1-42
Risk for Occupational Transmission of HCV
HCV is not transmitted efficiently through occupational exposures to blood. The average incidence of anti-HCV seroconversion after accidental percutaneous exposure from an HCV-positive source is 1.8% (range: 0%--7%) (73--76), with one study indicating that transmission occurred only from hollow-bore needles compared with other sharps (75). Transmission rarely occurs from mucous membrane exposures to blood, and no transmission in HCP has been documented from intact or nonintact skin exposures to blood (77,78). Data are limited on survival of HCV in the environment. In contrast to HBV, the epidemiologic data for HCV suggest that environmental contamination with blood containing HCV is not a significant risk for transmission in the health-care setting (79,80), with the possible exception of the hemodialysis setting where HCV transmission related to environmental contamination and poor infection-control practices have been implicated (81--84). The risk for transmission from exposure to fluids or tissues other than HCV-infected blood also has not been quantified but is expected to be low.
MSM: Men who have sex with men.
Scheinmann, Drug and Alcohol Dependence Weinbaum ,MMWR Gough, BMC Public Health Mast, J Infect Dis, Marincovich B, Sex Transm Infect Yaphe S, Sex Transm Inf Bottieau, Eurosurveillance Ackerman Z, J Viral Hepat Tohme RA, CID 2012 ; CDC/hepatitis.gov; CDC MMWR 2001; Hagan, et al, Int J Drug Policy 2007;

14. Perinatal Transmission of HCV
Transmission from HCV RNA + mothers
Mono-infected 6.5%
HIV –infected- 13.6%
Transmission risks
HCV viral load
< 6 log viral load- 3.9%
> 6 log viral load – 14.3%
Prolonged rupture of membranes( > 6 hours; OR 9.3)
Often cited but poor or no supportive data
Internal fetal monitoring
Vaginal versus cesarean delivery
No risk from breast feeding
No recommendations for maternal testing
Role of new antivirals yet to defined
Cottrell E, Ann Int Med 2013; Delotte J, J Matern Fetal Neonatal Med. 2014

15. Risk of Chronic infection and Disease Progression in HCV Infected Children
Chronic HCV infection
Perinatal exposures- 90%
Older children – 70-75%
Disease progression
Cause of 110 of 12,439 pediatric liver transplants ( )
Children appear to have less progressive disease than adults ( no alcohol or other co-factors)
On liver biopsy of 76 HCV+ children
35% no fibrosis
50%- mild fibrosis
4%- moderate/severe fibrosis
Severity related to age and duration of infection
New HCV meds not yet licensed for children
Abdel-Hady M. J Viral Hepat 2011; Robinso J, Liver Int 2012

16. Reported Number of Acute Hepatitis C cases — United States, 2000–2015
The number of reported cases of acute hepatitis C declined until 2003 and remained steady until 2010.  However, from , there was an approximate 2.9-fold increase in the number of reported acute hepatitis C cases from 850 to 2,436 cases.
Source: National Notifiable Diseases Surveillance System (NNDSS)

17. Incidence of Acute hepatitis C, by sex — United States, 2000–2014
Rates of acute hepatitis C decreased among males and females from 2000–2003 and remained fairly constant from 2004–2010.
From 2010–2014, rates of acute hepatitis C increased among males and females; in 2014, rates among males and females were 0.8 and 0.7 cases per 100,000 population, respectively.
Source: CDC, National Notifiable Diseases Surveillance System (NNDSS)

18. Proportion* of infants born to hepatitis C virus (HCV)-infected women† — United States and Kentucky, 2011–2014
1 of 67 births
~1600 infants born with HCV infection in 2014
1 of 308 births
* Proportion calculated annually as infants born to HCV-infected women divided by total infants born.
† HCV infection status of mother is determined by notation on infant’s birth certificate. Birth categorization is based on mother’s place of residence.

19. Reports of HCV among Pregnant Women, Kentucky December 2013 – July 2015
Need to explain HCV antibody+
HR Sands et al. Perinatal Hepatitis C Surveillance in Kentucky, Dec 2013-July 2015

20. Distribution of HCV Among Young Persons and Location of Syringe Service Programs
29,382 persons years with HCV
1 dot = 1 person
Syringe Service Program
HCV Cases: LabCorp and Quest commercial laboratories SSPs: North American Syringe Exchange Network
Figure shows persons aged who tested positive for HCV RNA between 2015q3-2016q2. SSPs are from 2016q2.
These commercial laboratories have limited coverage in the northern Midwest and pacific northwest.
Canary L, Hariri S, Campbell C, et al. “Geographic disparities in access to syringe service programs among young people with hepatitis C virus infection in the U.S.” November In Peer Review.

21. CDC and USPSTF Updated Recommendations for HCV Testing
One time screening test for persons born
Major risk
Past or present injection drug use
Other risks
Received blood/organs prior to June 1992
Received blood products made prior to 1987
Ever on chronic hemodialysis
Infants born to HCV infected mothers
Intranasal drug use
Unregulated tattoo
History of incarceration
Medical
Persistently elevated ALT
HIV
MMWR Aug Moyer VA, Ann Int Med 2013.

22. Improve HCV risk screening or routine testing
Considerations to Improve Prevention of HCV among Pregnant Women and their Children
Improve HCV risk screening or routine testing
Pregnant women, HCV exposed newborns: improve early identification of HCV-infected infants and linkage of the mother and infant to care and treatment
Women of reproductive age or in family planning- linkage to care, treatment, and cure to avoid HCV infection during pregnancy
Other newborns with illicit drug exposures (e.g. neonatal abstinence syndrome)
Frequency of testing, regional or national recommendations

23. Utilize existing data – birth certificate data
Considerations to Improve Prevention of HCV among Pregnant Women and their Children Surveillance
Utilize existing data – birth certificate data
Cross matching HCV and birth certificate registries ( e.g., Phil)
Mandated reporting of HCV among pregnant women, exposed infants and children (e.g, KY)
Reporting pregnancy status as part of HCV lab-based surveillance
DVH work group formed, expert consultation planned

24. Utilize existing data – birth certificate data
Considerations to Improve Prevention of HCV among Pregnant Women and their Children Next Steps
Utilize existing data – birth certificate data
Cross matching HCV and birth certificate registries ( e.g., Phil)
Mandated reporting of HCV among pregnant women, exposed infants and children (e.g, KY)
Reporting pregnancy status as part of HCV lab-based surveillance
DVH work group formed, expert consultation planned

25. Thank You