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
Objectives
• Review screening requirements for
pregnant women in Texas
• Review serological markers for
hepatitis B virus infections
Outline
• Historical perspective/rationale
• Screening requirements in Texas
• Serologic markers
– Importance of serologic markers
– Review serologic markers
• Acute infection
• Chronic infection
• Case Studies
Background Information
• 1991 hepatitis B screening of pregnant
women recommended by ACOG, AAP,
ACIP
• Risk of perinatal transmission
– HBsAg and HBeAg + at delivery - 70-90%
– HBsAg + only 5-20%
• 90% of infants infected perinatally will
become chronic carriers of hepatitis B
• 25% of those infected will die of HBVrelated disease
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
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
Screening Requirements in Texas –
Health and Safety Code, Chapter 81,
Section §81.090
Sec. 81.090. 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.
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.
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.
Summary of Requirement
• Women should be tested
– during pregnancy
And
– At delivery
• Women should be educated on
– Transmission
– Prevention
– Treatment
Serological Markers
Possible Outcomes
Outcomes of
Possible
of
Hepatitis B
B Infection
Infection
Hepatitis
Acute HBV
infection
Recovery
Chronic HBV
infection
Fulminant
hepatitis
Chronic hepatitis B
HBeAg-positive
HBsAg
carrier
Reactivation
Chronic hepatitis B
HBeAg-positive
Cirrhosis
HCC
Chronic hepatitis B
HBeAg-positive
HDV
superinfection
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 = 60-90 days)
• Communicability – 1 to 2 months before
and after onset of symptoms; chronic
carrier
Hepatitis B Lab Markers
Marker
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
Typical Serological Markers for
Acute Hepatitis B Infection
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Titer
HBsAg
0
4
8
12 16 20 24 28 32 36
Weeks after Exposure
52
100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Titer
HBV DNA
HBsAg
0
4
8
12 16 20 24 28 32 36
Weeks after Exposure
52
100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
HBeAg
Titer
HBV DNA
HBsAg
0
4
8
12 16 20 24 28 32 36
Weeks after Exposure
52
100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
HBeAg
anti-HBe
Titer
HBV DNA
HBsAg
0
4
8
12 16 20 24 28 32 36
Weeks after Exposure
52
100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Titer
HBV DNA
HBsAg
0
4
8
12 16 20 24 28 32 36
Weeks after Exposure
52
100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Titer
HBV DNA
IgM anti-HBc
HBsAg
0
4
8
12 16 20 24 28 32 36
Weeks after Exposure
52
100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Total anti-HBc
Titer
HBV DNA
IgM anti-HBc
HBsAg
0
4
8
12 16 20 24 28 32 36
Weeks after Exposure
52
100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Total anti-HBc
Titer
HBV DNA
IgM anti-HBc
anti-HBs
HBsAg
0
4
8
12 16 20 24 28 32 36
Weeks after Exposure
52
100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Total anti-HBc
Titer
HBV DNA
IgM anti-HBc
anti-HBs
HBsAg
Window
Period
0
4
8
12 16 20 24 28 32 36
Weeks after Exposure
52
100
Typical Serological Markers for
Chronic Hepatitis B Infection
Chronic Hepatitis B Virus Infection
Typical Serologic Course
Titer
HBsAg
0
1
2
3
4
5
6
Years After Exposure
7
8
9
10
Chronic Hepatitis B Virus Infection
Typical Serologic Course
HBsAg
Titer
Total anti-HBc
0
1
2
3
4
5
6
Years After Exposure
7
8
9
10
Chronic Hepatitis B Virus Infection
Typical Serologic Course
HBsAg
Titer
Total anti-HBc
HBV DNA
0
1
2
3
4
5
6
Years After Exposure
7
8
9
10
Chronic Hepatitis B Virus Infection
Typical Serologic Course
HBsAg
Titer
Total anti-HBc
IgM, anti-HBc
HBV DNA
0
1
2
3
4
5
6
Years After Exposure
7
8
9
10
Chronic Hepatitis B Virus Infection
Typical Serologic Course
HBeAg
HBsAg
Titer
Total anti-HBc
HBV DNA
0
1
2
3
4
5
6
Years After Exposure
7
8
9
10
Chronic Hepatitis B Virus Infection
Typical Serologic Course
HBeAg
Anti-HBe
HBsAg
Titer
Total anti-HBc
HBV DNA
0
1
2
3
4
5
6
Years After Exposure
7
8
9
10
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Acute
(6 months)
Chronic
(Years)
HBeAg
anti-HBe
HBsAg
Total anti-HBc
Titer
IgM anti-HBc
0 4 8 12 16 20 24 28 32 36
52
Weeks after Exposure
Years
Acute vs. Chronic HBV Infection
Acute
• 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+
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
Hepatitis B, perinatal
Surveillance Case Definition
• Confirmed:
– HBsAg-positive
– < 24 months of age
– Born to an HBsAg-positive woman
Hepatitis B, chronic
Surveillance Case Definition
• Confirmed: case that is laboratoryconfirmed (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
CASE STUDIES
Case Study A
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.
Question 1
What might his hepatitis B panel look like?
Answer
Marker
Result
HBsAg
Positive
HBeAg
Positive
anti-HBc
Positive
IgM anti-HBc
Positive
anti-HBeAg
Negative
anti-HBs
Negative
Case Study B
Sara visits his doctor and has a
hepatitis panel done. Her results are as
follows:
HBsAg
anti-HBc
IgM anti-HBc
anti-HBs
Positive
Positive
Negative
6mIU/mL
Question 1
How would you interpret Sara’s results?
Answer
• Chronic hepatitis B infection
Question 2
What significance is the anti-HBs?
Answer
• No biological significance
Case Study C
Jada went to her doctor for a routine
physical. A hepatitis panel was done
and her results were as follows:
HBsAg
anti-HBs
anti-HBc
Negative
Positive
Negative
Question 1
• How would you interpret her results?
Answer
• She received the hepatitis B vaccine
and is protected (immune)
Case Study D
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
Question 1
• How would you interpret his results?
Answer
• He has acute hepatitis B infection.
Case Study E
Stacy is pregnant. Her prenatal
HBsAg test was negative. Upon
admission for delivery, the HBsAg
screen was repeated. The results
came back positive.
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.
Question 1
• What tests should be ordered?
Answer
•
•
•
•
HBsAg
anti-HBc
anti-HBc, IgM
anti-HBs
Her results were as follows:
HBsAg
anti-HBs
anti-HBc
anti-HBc, IgM
Negative
Negative
Negative
Negative
How would you interpret?
Answer
• False positive
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 postpartum, Stacy’s physician decides to retest her. Her results are as follows:
HBsAg
Negative
anti-HBc
Positive
anti-HBs
Positive
Question 2
• What do the results indicate?
Answer
• Resolved Infection
Interpretation of Serological Tests
Test
Results
Interpretation
HBsAg
anti-HBc
anti-HBs
Negative
Negative
Negative
Susceptible
(Never infected or
vaccinated)
HBsAg
anti-HBc
anti-HBs
Negative
Negative
Positive
Immune
(Due to vaccine)
HBsAg
anti-HBc
anti-HBs
Negative
Positive
Positive
Immune
(Resolved Infection)
HBsAg
anti-HBc
IgM anti-HBc
anti-HBs
Positive
Positive
Positive
Negative
Acutely Infected
HBsAg
anti-HBc
anti-HBs
IgM anti-HBc
Positive
Positive
Negative
Negative
Chronically Infected
HBsAg
anti-HBc
anti-HBs
Negative
Positive
Negative
Four Possible
Interpretations
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 antiHBc
• May be undetectable level of HBsAg present
in the serum and the person is actually a
carrier
Summary
• Pregnant women should be screened
during pregnancy and at delivery
– Eliminate perinatal transmission
– Documentation necessary
• Determination of hepatitis status is
complicated
Resources
• American Academy of Pediatrics
Red Book – American Academy of Pediatrics (www.aap.org)
• DSHS
http://www.dshs.state.tx.us/idcu/disease/hepatitis/hepatitis_b/perinatal/Statistics/
• CDC
– Pink Book
http://www.cdc.gov/vaccines/pubs/pinkbook/default.htm
– On-line CE Training From CDC on Serological Markers
http://www.cdc.gov/hepatitis/Resources/Professionals/Training/SerologyStart.htm
– Online resources
http://www.cdc.gov/hepatitis/HBV/index.htm
• Immunization Action Coalition
http://www.immunize.org/hepatitis-b/