1. Emerging and Acute Infectious Disease Branch
Screening of Pregnant Women for Hepatitis B and Overview of Hepatitis B Virus Serological Markers
Rita Espinoza, MPH
Emerging and Acute Infectious Disease Branch
May 11, 2010

2. Objectives Review screening requirements for pregnant women in Texas
Review serological markers for hepatitis B virus infections

3. Outline Historical perspective/rationale
Screening requirements in Texas
Serologic markers
Importance of serologic markers
Review serologic markers
Acute infection
Chronic infection
Case Studies

4. Background Information
1991 hepatitis B screening of pregnant women recommended by ACOG, AAP, ACIP
Risk of perinatal transmission
HBsAg and HBeAg + at delivery %
HBsAg + only 5-20%
90% of infants infected perinatally will become chronic carriers of hepatitis B
25% of those infected will die of HBV-related disease

5. Strategies to Reduce HBV Disease
Continue and enhance vaccination efforts
School and childcare requirements
HCW
Adults (20-44 years)
Birth dose
Surveillance
Early detection
Education
Perinatal hepatitis B prevention program

6. Texas Rules Health & Safety Code, Chapter 81, Section §81.090
Texas Administrative Code, Title 25, Part 1, Chapter 97
Subchapter A, Rule §97.1 – §97.6
Subchapter F, Rule §97.135

7. Screening Requirements in Texas – Health and Safety Code, Chapter 81, Section §81.090
Sec   DIAGNOSTIC TESTING DURING PREGNANCY
AND AFTER BIRTH.  
(a)  A physician or other person permitted by law to attend a pregnant woman during gestation or at delivery of an infant shall:
(1)  take or cause to be taken a sample of the woman's blood or other appropriate specimen at the first examination and visit;
(2)  submit the sample to an appropriately certified laboratory for diagnostic testing approved by the United States Food and Drug Administration for:
(A)  syphilis;
(B)  HIV infection;  and
(C)  hepatitis B infection;  and
(3)  retain a report of each case for nine months and deliver the report to any successor in the case.

8. Screening Requirements in Texas – Health and Safety Code, Chapter 81, Section §81.090, (cont’d)
(a-1)  A physician or other person permitted by law to attend a pregnant woman during gestation or at delivery of an infant shall:
(1)  take or cause to be taken a sample of the woman's blood or other appropriate specimen at an examination in the third trimester of the pregnancy;
(2)  submit the sample to an appropriately certified laboratory for a diagnostic test approved by the United States Food and Drug Administration for HIV infection; and
(3)  retain a report of each case for nine months and deliver the report to any successor in the case.
(b)  A successor is presumed to have complied with this section if the successor in good faith obtains a record that indicates compliance with Subsections (a) and (a-1), if applicable.

9. Screening Requirements in Texas – Health and Safety Code, Chapter 81, Section §81.090, (cont’d)
(c)  A physician or other person in attendance at a delivery shall:
(1)  take or cause to be taken a sample of blood or other appropriate specimen from the mother on admission for delivery;  and
(2)  submit the sample to an appropriately certified laboratory for diagnostic testing approved by the United States Food and Drug Administration for:
(A)  syphilis; and
(B)  hepatitis B infection.

10. Summary of Requirement
Women should be tested
during pregnancy
And
At delivery
Women should be educated on
Transmission
Prevention
Treatment

11. Serological Markers

12. Possible Outcomes of
Hepatitis B Infection

13. Clinical Manifestations of HBV Infection
S/SX not unique to HBV infection
Only 50% of adult infections are symptomatic
Need diagnostic tests to distinguish
Incubation period - 45 to 180 days
(average = days)
Communicability – 1 to 2 months before and after onset of symptoms; chronic carrier

14. Hepatitis B Lab Markers
Abbreviation
Use
Hepatitis B surface antigen
HBsAg
Detection of acutely or chronically infected persons; antigen used in hepatitis B vaccine
M class immunoglobulin antibody to hepatitis B core antigen
IgM Anti-HBc
Anti-HBc, IgM
HBcAb, IgM
Identification of acute or recent HBV infections (including those in HBsAg-negative persons during the “window” phase of infection)
Antibody to hepatitis B core antigen
Anti-HBc
HBcAb
Identification of persons with acute, resolved, or chronic HBV infection
(not present after vaccination)
 Antibody to Hepatitis B surface antibody
Anti-HBs
HBsAb
Identification of persons who have resolved infection with HBV; determination of immunity after immunization
Hepatitis B e antigen
HBeAg
Identification of infected persons at increased risk for transmitting HBV
Antibody to Hepatitis B e antigen
Anti-HBe
HBeAb
Identification of infected person with lower risk for transmitting HBV
Read each marker. A chronic carrier is defined as someone whose HBsAg is positive for at least 6 months. Now let’s look at the interpretation of serological tests.

15. Typical Serological Markers for Acute Hepatitis B Infection

16. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Titer
HBsAg 4 8 12 16 20 24 28 32 36 52
100
Weeks after Exposure 30

17. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Titer
HBV DNA
HBsAg 4 8 12 16 20 24 28 32 36 52
100
Weeks after Exposure 30

18. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
HBeAg
Titer
HBV DNA
HBsAg 4 8 12 16 20 24 28 32 36 52
100
Weeks after Exposure 30

19. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
HBeAg
anti-HBe
Titer
HBV DNA
HBsAg 4 8 12 16 20 24 28 32 36 52
100
Weeks after Exposure 30

20. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Titer
HBV DNA
HBsAg 4 8 12 16 20 24 28 32 36 52
100
Weeks after Exposure 30

21. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Titer
IgM anti-HBc
HBV DNA
HBsAg 4 8 12 16 20 24 28 32 36 52
100
Weeks after Exposure 30

22. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Total anti-HBc
Titer
IgM anti-HBc
HBV DNA
HBsAg 4 8 12 16 20 24 28 32 36 52
100
Weeks after Exposure 30

23. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Total anti-HBc
Titer
IgM anti-HBc
HBV DNA
anti-HBs
HBsAg 4 8 12 16 20 24 28 32 36 52
100
Weeks after Exposure 30

24. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Total anti-HBc
Titer
IgM anti-HBc
HBV DNA
anti-HBs
HBsAg
Window Period 4 8 12 16 20 24 28 32 36 52
100
Weeks after Exposure 30

25. Typical Serological Markers for Chronic Hepatitis B Infection

26. Chronic Hepatitis B Virus Infection Typical Serologic Course
HBsAg

27. Chronic Hepatitis B Virus Infection Typical Serologic Course
HBsAg
Total anti-HBc

28. Chronic Hepatitis B Virus Infection Typical Serologic Course
HBsAg
Total anti-HBc
HBV DNA

29. Chronic Hepatitis B Virus Infection Typical Serologic Course
HBsAg
Total anti-HBc
IgM, anti-HBc
HBV DNA

30. Chronic Hepatitis B Virus Infection Typical Serologic Course
HBeAg
HBsAg
Total anti-HBc
HBV DNA

31. Chronic Hepatitis B Virus Infection Typical Serologic Course
HBeAg
Anti-HBe
HBsAg
Total anti-HBc
HBV DNA

33. Acute vs. Chronic HBV Infection
HBsAg+ < 6 mos.
IgM anti-HBc + positive
Infection will resolve and person will have lifelong immunity
HBsAb+ and HBcAb+
Chronic
HBsAg + for at least 6 months
Also known as a “carrier”
Infection does not resolve and the person remains infectious
HBsAb- and HBcAB+

34. Hepatitis B, acute Surveillance Case Definition
Confirmed:
Positive anti-HBc, IgM with or without symptoms or
Meets clinical case definition and is HBsAg-positive and anti-HAV IgM negative, if done

35. Hepatitis B, perinatal Surveillance Case Definition
Confirmed:
HBsAg-positive
< 24 months of age
Born to an HBsAg-positive woman

36. Hepatitis B, chronic Surveillance Case Definition
Confirmed: case that is laboratory-confirmed (2 positives 6 months apart or HBsAg+, anti-HBc+, and IgM-)
Probable: case with a single HBsAg or HBeAg or HBV DNA positive lab when no IgM anti-HBc results are available

37. CASE STUDIES

38. Case Study A

39. Patient History:
John went to his doctor with jaundice, fatigue and abdominal pain. After reviewing John’s liver panel, the doctor diagnosed him with acute hepatitis B infection.

40. Question 1
What might his hepatitis B panel look like?

41. Answer Marker Result HBsAg Positive HBeAg anti-HBc IgM anti-HBc
anti-HBeAg
Negative
anti-HBs

42. Case Study B

43. Sara visits his doctor and has a hepatitis panel done
Sara visits his doctor and has a hepatitis panel done. Her results are as follows:
HBsAg Positive
anti-HBc Positive
IgM anti-HBc Negative
anti-HBs 6mIU/mL

44. How would you interpret Sara’s results?
Question 1
How would you interpret Sara’s results?

45. Answer
Chronic hepatitis B infection

46. Question 2
What significance is the anti-HBs?

47. Answer
No biological significance

48. Case Study C

49. Jada went to her doctor for a routine physical
Jada went to her doctor for a routine physical. A hepatitis panel was done and her results were as follows:
HBsAg Negative
anti-HBs Positive
anti-HBc Negative

50. Question 1
How would you interpret her results?

51. Answer
She received the hepatitis B vaccine and is protected (immune)

52. Case Study D

53. Jeff went in for a routine annual physical
Jeff went in for a routine annual physical. His doctor decided to run a hepatitis panel. His results are as follows:
HBsAg Positive
anti-HBs Negative
anti-HBc Positive
anti-HBc, IgM Positive
HBeAg Positive

54. Question 1
How would you interpret his results?

55. Answer
He has acute hepatitis B infection.

56. Case Study E

57. Stacy is pregnant. Her prenatal HBsAg test was negative
Stacy is pregnant. Her prenatal HBsAg test was negative. Upon admission for delivery, the HBsAg screen was repeated. The results came back positive.

58. Scenario 1:
Stacy insisted that there was no way
she could have contracted hepatitis B.
she had not engaged in any high-risk
activities. The doctor decided to
repeat the test.

59. Question 1
What tests should be ordered?

60. Answer
HBsAg
anti-HBc
anti-HBc, IgM
anti-HBs

61. Her results were as follows:
HBsAg Negative
anti-HBs Negative
anti-HBc Negative
anti-HBc, IgM Negative
How would you interpret?

62. Answer
False positive

63. Scenario 2:
Stacy’s baby received the HBIG and
hepatitis B vaccine at birth. The family is
enrolled in the local perinatal hepatitis B
prevention program. Three months post-
partum, Stacy’s physician decides to re-
test her. Her results are as follows:
HBsAg Negative
anti-HBc Positive
anti-HBs Positive

64. Question 2
What do the results indicate?

65. Answer
Resolved Infection

66. Interpretation of Serological Tests
Results
Interpretation
HBsAg
anti-HBc
anti-HBs
Negative
Susceptible
(Never infected or vaccinated)
Positive
Immune
(Due to vaccine)
(Resolved Infection)
IgM anti-HBc
Acutely Infected
Chronically Infected
Four Possible Interpretations

67. Four Possible Interpretations
May be recovering from acute HBV infection
May be distantly immune and test not sensitive enough to detect very low level of anti-HBs in serum
May be susceptible with a false positive anti-HBc
May be undetectable level of HBsAg present in the serum and the person is actually a carrier

68. Summary
Pregnant women should be screened during pregnancy and at delivery
Eliminate perinatal transmission
Documentation necessary
Determination of hepatitis status is complicated

69. Resources American Academy of Pediatrics
Red Book – American Academy of Pediatrics (
DSHS
CDC
Pink Book
On-line CE Training From CDC on Serological Markers
Online resources
Immunization Action Coalition