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Hepatitis B Virus  (HBV)

Hepatitis B virus (HBV) is a double-stranded DNA virus in the Hepadnaviridae family. The transmission electron micrograph (TEM) at right shows numerous hepatitis B virus (HBV) virions, also known as Dane particles. In infected persons HBV is found in highest concentrations in the blood, and lower concentrations in saliva, semen, vaginal secretions, and wound exudates. HBV can remain viable for >7 days on environmental surfaces at room temperature.

The average incubation period is 90 days from time of exposure to onset of symptoms, but may vary from 6 weeks to 6 months [1,2,5].

Acutely infected individuals develop clinically apparent hepatitis with loss of appetite, nausea, vomiting, fever, abdominal pain and jaundice [1]. Some may have dark urine and gray stool [2] . About one half of acute HBV infections in adults are symptomatic . About 1% of cases result in acute liver failure and death.

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Betty Partin

Sexual transmission accounts for most adult HBV infections in the United States [1]. Approximately 25% of the regular sexual contacts of infected individuals will themselves become seropositive. [2]

10-20% of women seropositive for HBsAg transmit the virus to their neonates in the absence of immunoprophylaxis. In women who are seropositive for both HBsAg and HBeAg vertical transmission is approximately 90% [2]. In patients with acute hepatitis B vertical transmission occurs in up to 10% of neonates when infection occurs in the first trimester and in 80 -90% of neonates when acute infection occurs in the third trimester [2].

Sequelae

Chronic infection occurs in about 90% of infected infants, 30% of infected children aged <5 years , and 2%--6% of adults. Among persons with chronic HBV infection, the risk of death from cirrhosis or hepatocellular carcinoma is 15%--25%. [1]

HBV infection does not appear to be cause birth defects, but there appears to be a higher incidence of low birth weight among infants born to mothers with acute infection during pregnancy [3]. In one small study acute maternal hepatitis (type B or nontype B) had no effect on the incidence of congenital malformations, stillbirths, abortions, or intrauterine malnutrition. However, acute hepatitis did increase the incidence of prematurity [4].

Who to test [1]

  • Test all pregnant women at the first prenatal visit for hepatitis B surface antigen (HBsAg).
  • Women admitted for delivery who have not had prenatal HBsAg testing should have blood drawn for testing [5].
  • Send a copy of the original lab report to the hospital.
  • “More than 90% of women found to be HBsAg-positive on routine screening will be HBV carriers, routine follow-up testing later in pregnancy is not necessary for the purpose of screening. In special situations, such as when the mother is thought to have acute hepatitis, when there has been a history of exposure to hepatitis, or when particularly high-risk behavior such as parenteral drug abuse has occurred during the pregnancy, an additional HBsAg test can be ordered during the third trimester” [6]
  • Test all susceptible contacts (including all family members) with hepatitis B panel (HBsAg, antiHBc, antiHBs).
  • Screening and vaccination of susceptible contacts should be done by the family's pediatrician, primary health-care provider, or the physician evaluating the clinical status of the HBsAg-positive pregnant women.

Interpretation of the Hepatitis B Panel Tests Results Interpretation

Tests

Results

 Interpretation

HBsAg
anti-HBc
anti-HBs

negative
negative
negative

   
susceptible
  

HBsAg
anti-HBc
anti-HBs

negative
positive
positive

  
 immune due to natural infection
   

HBsAg
anti-HBc
anti-HBs

negative
negative
positive

immune due to hepatitis B vaccination

HBsAg
anti-HBc
IgM anti-HBc
anti-HBs

positive
positive
positive
negative

  
acutely
infected
  

HBsAg
anti-HBc
IgM anti-HBc
anti-HBs

positive
positive
negative
negative

   
chronically
infected
   

HBsAg
anti-HBc
anti-HBs

negative
positive
negative

four
interpretations
possible *

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

Source: http://www.cdc.gov/ncidod/diseases/hepatitis/b/Bserology.htm
Accessed May 7, 2008
 

The presence of  HBsAg idicates ongoing HBV infection, and in newly infected persons, HBsAg is the only serologic marker detected during the first 3--5 weeks after infection. In persons who recover from HBV infection, HBsAg is usually eliminated from the blood in  3--4 months, and anti-HBs develops [5].

A positive HBsAg in the absence of IgM anti-HBc is indicative of chronic infection. If positive, this test result should be reported to state perinatal immunization or HBV prevention programs to ensure proper case management of the mother and appropriate postexposure immunization of her at-risk infant [1]. The baby's health-care provider should be notified about the mother's HBsAg-positive status and receive hepatitis B immune globulin (HBIG) and HBV vaccine.
 

Prevention [2]

Two available  hepatitis B vaccines for immunization are Recombivax HB® (Merck and Co., Inc.) and Engerix-B (SmithKline Beecham Biologicals).

  • Pregnancy is not a contraindication to vaccination. 
  • For vaccination of adults 20 years of age and older:
    •  1-mL dose by intramuscular injection into the deltoid muscle, at initial visit, then one month and six months after the first dose, for a total of three doses
    • Consult package inserts for details.


Postexposure Prophylaxis for Susceptible Pregnant Women [1, 13]

    After Exposure to Persons Who Have Acute Hepatitis B
    When exposure has occurred as a result of sexual contact within 14 days after the most recent sexual contact administer

      • A course of HBV vaccine into the deltoid as above
      • A dose of Hepatitis B immune globulin (HBIG) 0.06 mL/kg IM into the contralateral arm.
        • For prophylaxis after percutaneous or mucous membrane injury, a second dose of HBIG should be given 1 month later.

      Exposure to Persons Who Have Chronic HBV Infection

      • Active postexposure prophylaxis with hepatitis B vaccine alone is recommended for sex or needle-sharing partners and non-sexual household contacts of persons with chronic HBV infection

 

Newborns Born to Hepatitis B Carriers [2]

  • Newborns born to hepatitis B carriers should receive hepatitis vaccine AND hepatitis B immune globulin (HBIG) within 12 hours of birth.
     

Treatment

The treatment of acute HBV infection is supportive. Patients should be hospitalized if they have coagulopathy, encephalopathy , or severe debilitation [2]. 

Persons with chronic hepatitis B should be referred to health-care professionals with experience in the treatment of hepatitis B for treatment with alpha-interferon or lamivudine [1]. Interferon does not appear to adversely affect the embryo or fetus. However, the data is limited, and the potential benefits of interferon use during pregnancy should clearly outweigh possible hazards [7-9]. Initial data do not suggest that Lamivudine is teratogenic [10]. Lamivudine has been used in the latter half of pregnancy in attempt to prevent perinatal transmission of hepatitis B virus infection with mixed success [11,12]
 

Antepartum

Pregnant Hepatitis B carriers should be advised to


  • Obtain vaccination against hepatitis viruses A as indicated.
  • Abstain form alcohol use
  • Avoid hepatotoxic drugs such as acetaminophen (Tylenol) that may worsen liver damage.
  • Not donate blood, body organs, or other tissue.
  • Not share any personal items that may have blood on them (e.g., toothbrushes and razors).
  • Inform the infant’s pediatrician, OB/GYN, and labor staff that they are a hepatitis B carrier.
  • Make sure their baby receives hepatitis B vaccine at birth, one month, and six months of age as well as H-BIG at birth.
  • Be seen at least annualy by their regular medical doctor.
  • Discuss the risk for transmission with their partner and discuss the need for counseling and testing
  • Liver function testing is recommended for women who test positive for HBsAg [1]


The following recommendations from The Society of Obstetricians and Gynecologists of Canada may be helpful in counseling women considering amniocentesis.

    SOGC Recommendations [14]

    • “The risk of fetal hepatitis B infection through amniocentesis is low. However, knowledge of the maternal hepatitis B e antigen status is valuable in the counselling of risks associated with amniocentesis.
    • For women infected with hepatitis B, hepatitis C, or HIV, the addition of noninvasive methods of prenatal risk screening, such as nuchal translucency, triple screening, and anatomic ultrasound, may help in reducing the age-related risk to a level below the threshold for genetic amniocentesis.
    • For those women infected with hepatitis B, hepatitis C, or HIV who insist on amniocentesis, every effort should be made to avoid inserting the needle through the placenta. “

Delivery

Although cesarean delivery has been proposed as a means of reducing mother to child transmission (MCT) of HBV [15] The mode of delivery does not appear to have a significant effect on the interruption of HBV maternal-baby transmission by immunoprophylaxis [16]. Delivery by cesarean section for the purpose of reducing MCT of HBV is note presently recommended by either the CDC [1] or the ACOG [2].


Breast feeding

With appropriate hepatitis B immunoprophylaxis, breast-feeding poses no additional risk for transmission from infected hepatitis B virus carriers [17,18]

 

ADDITIONAL RESOURCES:

  • Viral Hepatitis
        Centers for Disease Control
  • HepBMoms.org
        Stanford University
  • Tan HH, et al.,.Chronic hepatitis B virus (HBV) infection in pregnancy.
    Hepatol Int. 2008 Sep;2(3):370-5. PMID: 19669267
  • Lin K, Vickery J..Screening for hepatitis B virus infection in pregnant women: evidence for the U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med. 2009 Jun 16;150(12):874-6. PMID: 19528566. PMID: 19669267
  • Tran TT.Management of hepatitis B in pregnancy: weighing the options.Cleve Clin J Med. 2009 May;76 Suppl 3:S25-9.PMID: 19465706
  • Reynaud L, et al.Tenofovir and its potential in the treatment of hepatitis B virus. Ther Clin Risk Manag. 2009 Feb;5(1):177-85. Epub 2009 Mar 26.PMID: 19436619
  • Chatterjee S, et al. Hepatitis B Prevalence during pregnancy.Indian Pediatr. 2009 Nov;46(11):1005-8. PMID: 19430075
  • Elefsiniotis IS, et al. Surveillance for hepatitis B virus infection in pregnant women in Greece shows high rates of chronic infection among immigrants and low vaccination-induced protection rates: preliminary results of a single center study.Euro Surveill. 2009 Mar 5;14(9):5-7.PMID: 19317974
  • Lima LH, Viana MC. Prevalence and risk factors for HIV, syphilis, hepatitis B, hepatitis C, and HTLV-I/II infection in low-income postpartum and pregnant women in Greater Metropolitan Vitória, Espírito Santo State, Brazil.Cad Saude Publica. 2009 Mar;25(3):668-76.PMID: 19300855
  • Resuli B, et al.Epidemiology of hepatitis B virus infection in Albania.World J Gastroenterol. 2009 Feb 21;15(7):849-52.PMID: 19230046
  • Jara P, Bruguera M.[Hepatitis B in pregnant women and children.] Enferm Infecc Microbiol Clin. 2008 May;26 Suppl 7:66-70. PMID: 19100233
  • Hung JH, et al., Lamivudine therapy in the treatment of chronic hepatitis B with acute exacerbation during pregnancy.J Chin Med Assoc. 2008 Mar;71(3):155-8.PMID: 18364269
  • Bhattacharya S, et al Ante-natal screening and post-natal follow-up of hepatitis B in the West Midlands of England. QJM. 2008 Apr;101(4):307-12. PMID: 18281704
  • Bai H, et al. Relationship of hepatitis B virus infection of placental barrier and hepatitis B virus intra-uterine transmission mechanism. World J Gastroenterol. 2007 Jul 14;13(26):3625-30.
    PMID: 17659715
     

REFERENCES:
1. Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006 Aug 4;55(RR-11):1-94. Erratum in: MMWR Recomm Rep. 2006 Sep 15;55(36):997. PMID:16888612
2. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 86: Viral hepatitis in pregnancy.Obstet Gynecol. 2007 Oct;110(4):941-56. PMID: 17906043
3. Shepard TH. Catalog of Teratogenic Agents pp 1309. 9th ed.Baltimore, MD: Johns Hopkins University Press ,1998 .p1309
4. Hieber JP, Dalton D, Shorey J, Combes B. Hepatitis and pregnancy.J Pediatr. 1977 Oct;91(4):545-9. PMID: 561834
5. Mast EE,et al. Advisory Committee on Immunization Practices (ACIP).comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005 Dec 23;54(RR-16):1-31.PMID: 16371945
6. Recommendations of the Immunization Practices Advisory Committee Prevention of Perinatal Transmission of Hepatitis B Virus: Prenatal Screening of all Pregnant Women for Hepatitis B Surface Antigen MMWR June 10, 1988 / 37(22);341-6,351
7. Briggs GG,Freeman RK, Yaffe SJ, Drugs in Pregnancy and Lactation 7th edition,Baltimore, MD: 2005 p 836 -838.
8. Ozaslan E, Yilmaz R, Simsek H, Tatar G. Interferon therapy for acute hepatitis C during pregnancy.
Ann Pharmacother. 2002;36:1715-8.PMID: 12398565
9. Hiratsuka M, Minakami H, Koshizuka S, Sato I. Administration of interferon-alpha during pregnancy: effects on fetus. J Perinat Med. 2000;28(5):372-6.PMID: 11125927
10. Briggs GG,Freeman RK, Yaffe SJ, Drugs in Pregnancy and Lactation 7th edition,Baltimore, MD: 2005 p 889 -893.
11. van Zonneveld M, van Nunen AB, Niesters HG, de Man RA, Schalm SW, Janssen HL. Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection.J Viral Hepat. 2003 ;10(4):294-7. PMID: 12823596
12. Kazim SN, Wakil SM, Khan LA, Hasnain SE, Sarin SK. Vertical transmission of hepatitis B virus despite maternal lamivudine therapy. Lancet. 2002;359(9316):1488-9 PMID: 11988251
13. Centers for Disease Control. Protection against viral hepatitis. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1990;39(RR-2):1-26. PMID: 2153904

14. Davies G et al Society of Obstetricians and Gynaecologists of Canada. Amniocentesis and women with hepatitis B, hepatitis C, or human immunodeficiency virus. J Obstet Gynaecol Can. 2003 ;25(2):145-48, 149-52. PMID: 12577132
15. Lee SD, Lo KJ, Tsai YT, Wu JC, Wu TC, Yang ZL, Ng HT. The role of cesarean section in the prevention of mother-infant transmission of hepatitis B virus. Lancet. 1988;2:833-4. PMID: 2902274
16. Wang J, Zhu Q, Zhang X. Effect of delivery mode on maternal-infant transmission of hepatitis B virus by immunoprophylaxis. Chin Med J (Engl) 2002 Oct;115(10):1510-2 PMID: 12490098
17. Hill JB et al , Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers.
Obstet Gynecol. 2002 ;99(6):1049-52. PMID: 12052598
18. Wang JS, Zhu QR, Wang XH. Breastfeeding does not pose any additional risk of immunoprophylaxis failure on infants of HBV carrier mothers. Int J Clin Pract. 2003 ;57(2):100-2.PMID: 12661791

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