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

Rita Espinoza, MPHEmerging and Acute Infectious Disease Branch

May 11, 2010

Screening of Pregnant Women for Hepatitis B and Overview of Hepatitis B

Virus Serological Markers

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 HBV-related 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 PREGNANCYAND 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.


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.


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 of Hepatitis B Infection

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 MarkersMarker 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

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100

Acute Hepatitis B Virus Infection with RecoveryAcute Hepatitis B Virus Infection with RecoveryTypical Serologic CourseTypical Serologic Course

Weeks after ExposureWeeks after Exposure

TiterTiter

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBV DNA

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBV DNA

HBeAg

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

HBV DNA

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

Symptoms

HBV DNA

IgM anti-HBcIgM anti-HBc

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

Symptoms

HBV DNA


HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

Symptoms

Total anti-HBcTotal anti-HBc

HBV DNA


HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

Symptoms

anti-HBsanti-HBs


HBV DNA


HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

Symptoms

anti-HBsanti-HBs


HBV DNA

Window Period

Typical Serological Markers for Chronic Hepatitis B Infection

Chronic Hepatitis B Virus Infection Typical Serologic CourseTypical Serologic Course

0 1 2 3 4 5 6 7 8 9 10

Tite

r

Years After Exposure

HBsAg

0 1 2 3 4 5 6 7 8 9 10

Tite

r


HBsAg

Total anti-HBc


0 1 2 3 4 5 6 7 8 9 10

Tite

r


HBsAg

Total anti-HBc

HBV DNA


0 1 2 3 4 5 6 7 8 9 10

Tite

r


HBsAg

Total anti-HBc

HBV DNA

IgM, anti-HBc


0 1 2 3 4 5 6 7 8 9 10

Tite

r


HBsAg

Total anti-HBc

HBV DNA

HBeAg


0 1 2 3 4 5 6 7 8 9 10

Tite

r


HBsAg

Total anti-HBc

HBV DNA

HBeAg Anti-HBe


Progression to Chronic Hepatitis B Virus InfectionProgression to Chronic Hepatitis B Virus InfectionTypical Serologic CourseTypical Serologic Course


TiterTiter

IgM anti-HBc

Total anti-HBc

HBsAg

Acute(6 months)

HBeAg

Chronic(Years)

anti-HBe

0 4 8 12 16 20 24 28 32 36 52 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, chronicSurveillance 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

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 Positive

anti-HBc Positive

IgM anti-HBc Negative

anti-HBs 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 Negative

anti-HBs Positive

anti-HBc 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 Negative

anti-HBs Negative

anti-HBc Negative

anti-HBc, IgM Negative

How would you interpret?

Answer

• False positive

Scenario 2: Stacy’s baby received the HBIG andhepatitis B vaccine at birth. The family isenrolled in the local perinatal hepatitis Bprevention program. Three months post-partum, Stacy’s physician decides to re-test her. Her results are as follows:

HBsAg Negativeanti-HBc Positiveanti-HBs Positive

Question 2

• What do the results indicate?

Answer

• Resolved Infection

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

Interpretation of Serological Tests

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

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 PediatricsRed Book – American Academy of Pediatrics (www.aap.org)

• DSHShttp://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 Markershttp://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/

Documents

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