Hepatitis B Virus - HBV

  • Diagnosis
  • Algorithms
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics
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Indications for Testing

  • New onset of jaundice, anorexia, or dark urine
  • Known exposure to hepatitis
  • Suspicion of chronic hepatitis (elevated liver enzymes)
  • Initial screening for acute hepatitis indicates hepatitis B (HBV) infection

Criteria for Diagnosis

Laboratory Testing

  • Testing and treatment recommendations (CDC, 2016)
  • Differentiate between acute and chronic hepatitis
    • If acute HBV is suspected, test as follows
      •  To determine HBV status
        • HBV core antibody (anti-HBc) IgM
        • HBV surface antigen (HBsAg)
      • To determine alternative or coinfection
    • Interpretation
      • Positive anti-HBc IgM and HBsAg confirm acute HBV
      • If either HBsAg or HBV DNA test is positive, patient is contagious
    • If HBsAg is positive for >6 months – chronic HBV
      • To determine whether active or inactive, test
        • Hepatitis Be antigen (HBeAg)
        • Anti-HBe
        • HBV DNA
      • Interpretation
        • Active chronic disease
          • HBeAg positive, anti-HBe negative, and high HBV DNA; or
          • HBeAg negative, anti-HBe positive, and high HBV DNA
        • Inactive chronic disease
          • HBeAg negative, anti-HBe positive, and undetectable or low HBV DNA
  • Test all patients with chronic HBV for HCV
  • Test for coinfection/superinfection with hepatitis D (HDV) in patients with known HBV and acute deterioration
  • Liver biopsy (Papatheodoridis, European Association for the Study of the Liver [EASL], 2009; Lok, American Association for the Study of Liver Diseases [AASLD], 2009) 
    • Patients with evidence of active disease – elevated transaminases and DNA >2,000 IU/mL
    • Results may guide therapy in active disease
    • Useful when noninvasive testing does not suggest advanced fibrosis

Differential Diagnosis

Screening Recommendations for HBV

Population

Screening Recommendation

Persons born in regions of high and intermediate HBV prevalence (>2%) (eg, Africa, Asia Pacific)

CDC, 2016

Injection-drug abusers

CDC, 2016

Men who have sex with men

CDC, 2016

Patients undergoing hemodialysis

CDC, 2016

All pregnant women

CDC, 2016

Infants born to HBsAg-positive mothers

CDC, 2016

Donors of blood, plasma, organs, tissue, and semen

Code of Federal Regulations (FDA)

U.S.-born persons not vaccinated as infants whose parents were born in region of high HBV prevalence (>8%)

CDC, 2016

Persons with elevated ALT/AST of unknown etiology

CDC, 2016

HIV-positive persons

CDC, 2016

Household, needle sharing, or sexual contact with individuals known to be HBsAg positive

CDC, 2016

Persons who are sources for exposures (needlestick, sexual assault)

CDC, 2004

Individuals needing immunosuppressive therapy (for transplant, rheumatology, and gastroenterology)

CDC, 2016

ALT = alanine aminotransferase; AST = aspartate aminotransferase; FDA = Food and Drug Administration; HBsAg = HBV surface antigen; HBV = hepatitis B virus

CDC, 2016; Lok, American Association for the Study of Liver Diseases [AASLD], 2009

Population

Screening 
recommendation

Persons born in regions of high and intermediate HBV prevalence (>2%) (eg, Africa, Asian-Pacific)

CDC 2008

Injection-drug abusers

CDC 2008

Men who have sex with men

CDC 2008

Hemodialysis

CDC 2001

All pregnant women

CDC 2005

Infants born to HBsAg-positive mothers

CDC 2005, 2007, 2008

Donors of blood, plasma, organs, tissue, and semen

Code of Federal Regulations (FDA)

US-born persons not vaccinated as infants whose parents were born in region of high HBV prevalence (>8%)

CDC 2008

Persons with elevated ALT/AST of unknown etiology

CDC 2008

HIV-positive persons

CDC 2004

Household, needle-sharing or sex contacts of persons known to be HBsAg positive

CDC 2005

Persons who are sources for exposures (needle-stick, sexual assault)

CDC 2004

Persons needing immunosuppressive therapy (transplant, rheumatology, and gastroenterology)

CDC 2008

  • Monitor chronic disease at least annually (WHO, 2017)
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels
    • Hepatitis B virus surface antigen (HBsAg), hepatitis Be antigen (HBeAg), anti-HBe, anti-HBs, HBV DNA levels, transaminases
    • AST-to-platelet ratio (APRI) or transient elastography to assess fibrosis/cirrhosis
  • More frequent monitoring recommended for
    • Patients receiving treatment or after treatment discontinuation
    • Patients who do not yet meet criteria for antiviral therapy

Hepatitis B (HBV) is a blood-borne virus and one of the most common infectious diseases in the world.

Epidemiology

  • Incidence
    • ~30% of the world population has been exposed (Trepo, 2014)
      • 350 million – chronically infected
    • Endemic in Asia, sub-Saharan Africa, Pacific Islands, and parts of Latin America
    • Chronic disease in U.S. – <2%
      • Cases have decreased by 80% with vaccination
  • Transmission
    • Parenteral – common infection route in low-prevalence regions
    • Sexual – common infection route in low-prevalence regions
    • Vertical perinatal – main infection route in endemic regions
    • Horizontal – from chronically infected person within a household
  • Ethnicity – more common in Alaskan native and Pacific Islander populations

Organism

  • DNA virus of Hepadnaviridae family
  • At least 10 HBV subgroups (A-J) based on genetic differences
    • Genotypes tend to be geographically based
    • Genotype A most common in North America, Northern Europe
    • Genotype may be associated with disease progression and response to treatment
    • Each subgroup may have subtypes (eg, A1, A2, A3)
  • Infection not directly cytotoxic to hepatocytes – severity of injury is modulated by host immune responses
  • High titers of HBV are present in blood; moderate titers are present in vaginal secretions, semen, and saliva

Risk Factors

  • Parenteral drug abuse
  • Multiple sex partners (>1 partner during the preceding 6 months)
  • HBV-positive partner
  • HIV infection
  • Needlestick
    • 1-6% risk if blood is hepatitis B surface antigen (HBsAg) positive
    • 22-40% risk if blood is HBsAg positive and hepatitis Be antigen (HBeAg) positive
  • Hemodialysis
  • Blood transfusion (predominantly in developing countries)
  • Membership in a high-risk group
    • Infants of HBV-infected mothers
    • Alaskan native and Pacific Islander children
    • Men who have sex with men (MSM)
    • Children residing in households of first-generation immigrants from countries where HBV infection is endemic

Pathophysiology

  • Infants and young children are at the greatest risk for becoming chronically infected
    • 95% of perinatal transmission occurs at time of birth
      • 5-20% risk if mother is HBsAg positive
      • 70-90% risk if mother is HBsAg and HBeAg positive
    • 90% of exposed infants will develop chronic hepatitis
    • 30% of exposed children ages 1-5 will develop chronic hepatitis
    • Only 5% of exposed adults will develop chronic hepatitis
  • Breastfeeding does not increase risk and need not be discontinued by an infected mother

Clinical Presentation

  • Acute HBV
    • Likelihood of developing symptoms is age dependent
      • Children generally asymptomatic
      • Adults and adolescents more likely to be symptomatic
    • Incubation period of 2 weeks to 4 months
    • Mildest disease is asymptomatic, anicteric, and detectable only by an increase in serum transaminase levels
    • Influenza-like symptoms – fatigue, malaise, fever, anorexia
    • Jaundice and gastrointestinal symptoms (usually within 10 days of symptom onset)
    • May develop acute fulminant hepatic failure requiring transplantation (~1% of cases)
      • Rapidly progressive hepatitis with signs of liver failure – coagulopathy, encephalopathy, cerebral edema
  • Chronic HBV
    • Most common presentation is fatigue or vague discomfort in right-upper quadrant
    • Patients may have systemic symptoms associated with deposition of circulating hepatitis B antigen-antibody immune complexes (eg, arthritis, leukocytoclastic vasculitis, glomerulonephritis, cryoglobulinemia, and generalized vasculitis)
    • Long-term consequences include cirrhosis and hepatocellular carcinoma (HCC)
      • Cirrhosis may present with jaundice, ascites, splenomegaly, encephalopathy, or variceal bleeding
    • Annual incidence of HCC
      • <1% for noncirrhotic HBV-infected “carriers”
      • 2-3% for patients with cirrhosis
    • Annual incidence of cirrhosis
      • 2-6% for HBeAg-negative patients
      • 8-10% for HBeAg-positive chronic hepatitis patients

Prevention

  • Vaccination recommended for
    • Persons residing in communities with an increased prevalence of infection
    • Persons traveling to a country with high prevalence rates
    • Healthcare workers
    • All neonates and children
    • HIV-positive patients
    • Residents of correctional facilities
  • Immediate short-term protection (3-6 months) against HBV can be obtained with hepatitis B IgG
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Hepatitis Panel, Acute with Reflex to HBsAg Confirmation 0020457
Method: Qualitative Chemiluminescent Immunoassay

Hepatitis B Virus Surface Antigen with Reflex to Confirmation 0020089
Method: Qualitative Chemiluminescent Immunoassay 

Hepatitis B Virus Surface Antibody 0020090
Method: Quantitative Chemiluminescent Immunoassay

Limitations 

Do not use for blood donor screening, associated reentry protocols, or for screening human cell, tissues, and cellular and tissue-based products

Hepatitis B Virus Core Antibody, IgM 0020092
Method: Qualitative Chemiluminescent Immunoassay

Hepatitis B Virus Core Antibodies (Total) 0020091
Method: Qualitative Chemiluminescent Immunoassay

Limitations 

Tests for IgG and IgM antibodies but does not differentiate between them 

Hepatitis Be Virus Antigen 0020094
Method: Qualitative Enzyme Immunoassay

Limitations 

Order only when a patient is known to be positive for HBsAg

Hepatitis Be Virus Antibody 0020095
Method: Qualitative Enzyme Immunoassay

Hepatitis Be Virus Antigen and Antibody Panel 2012141
Method: Qualitative Enzyme Immunoassay

Hepatitis B Virus Surface Antigen with Reflex to Confirmation, Prenatal 2007573
Method: Qualitative Chemiluminescent Immunoassay 

Hepatitis B Virus by Quantitative PCR 0056025
Method: Quantitative Polymerase Chain Reaction

Hepatitis B Virus (HBV) by Quantitative PCR with Reflex to HBV Genotype by Sequencing 2004722
Method: Quantitative Polymerase Chain Reaction/Sequencing

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Guidelines

Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009; 50(3): 661-2. PubMed

Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein ST, Wang SA, Moyer LA, Bell BP, Alter MJ, Advisory Committee on Immunization Practices (ACIP). A 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; 54(RR-16): 1-31. PubMed

Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, Rodewald LE, Douglas JM, Janssen RS, Ward JW, Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). A 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 II: immunization of adults. MMWR Recomm Rep. 2006; 55(RR-16): 1-33; quiz CE1-4. PubMed

McHugh JA, Cullison S, Apuzzio J, Block JM, Cohen C, Leong SL, London T, McNellis RJ, Neubauer RL, Perrillo R, Squires R, Tarrant D, McMahon BJ. Chronic hepatitis B infection: a workshop consensus statement and algorithm. J Fam Pract. 2011; 60(9): E1-8. PubMed

Papatheodoridis GV, Manolakopoulos S. EASL clinical practice guidelines on the management of chronic hepatitis B: the need for liver biopsy. J Hepatol. 2009; 51(1): 226-7. PubMed

Schillie S, Murphy TV, Sawyer M, Ly K, Hughes E, Jiles R, de Perio MA, Reilly M, Byrd K, Ward JW, Centers for Disease Control and Prevention (CDC). CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013; 62(RR-10): 1-19. PubMed

Sorrell MF, Belongia EA, Costa J, Gareen IF, Grem JL, Inadomi JM, Kern ER, McHugh JA, Petersen GM, Rein MF, Strader DB, Trotter HT. National Institutes of Health consensus development conference statement: management of hepatitis B. Hepatology. 2009; 49(5 Suppl): S4-S12. PubMed

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC). Adult Immunization Schedule. Center for Disease Control and Prevention. [Last updated Feb 2017; Accessed: Sep 2017]

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC). The ABCs of Hepatitis. Center for Disease Control and Prevention. Atlanta, GA [Last updated 2016; Accessed: Sep 2017]

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC). Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011; 60(50): 1709-11. PubMed

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC).. Updated CDC recommendations for the management of hepatitis B virus-infected health-care providers and students. MMWR Recomm Rep. 2012; 61(RR-3): 1-12. PubMed

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Manual for the Surveillance of Vaccine-Preventable Diseases. Centers for Disease Control and Prevention. Atlanta, GA [Last updated Apr 2016; Accessed: Aug 2017]

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Recommended Immunization Schedules for Children and Adolescents Aged 18 Years or Younger. United States, 2016. Centers for Disease Control and Prevention. Atlanta, GA [Last Updated Jan 2017; Accessed: Sep 2017]

U.S. Preventive Services Task Force. Screening for hepatitis B virus infection in pregnancy: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med. 2009; 150(12): 869-73, W154. PubMed

Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, Neitzel SM, Ward JW, Centers for Disease Control and Prevention (CDC). Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008; 57(RR-8): 1-20. PubMed

Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015; 64(RR-03): 1-137. PubMed

General References

Chakravarty R. Role of molecular diagnostics in the management of viral hepatitis B. Expert Opin Med Diagn. 2012; 6(5): 395-406. PubMed

Davison SA, Strasser SI. Ordering and interpreting hepatitis B serology. BMJ. 2014; 348: g2522. PubMed

Elgouhari HM, Tamimi TI, Carey W. Hepatitis B: a strategy for evaluation and management. Cleve Clin J Med. 2009; 76(1): 19-35. PubMed

Kuo A, Gish R. Chronic hepatitis B infection. Clin Liver Dis. 2012; 16(2): 347-69. PubMed

McMahon BJ. Chronic hepatitis B virus infection. Med Clin North Am. 2014; 98(1): 39-54. PubMed

Morrison BJ, Labo N, Miley WJ, Whitby D. Serodiagnosis for tumor viruses. Semin Oncol. 2015; 42(2): 191-206. PubMed

Pourkarim MR, Amini-Bavil-Olyaee S, Kurbanov F, Van Ranst M, Tacke F. Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions. World J Gastroenterol. 2014; 20(23): 7152-68. PubMed

Shiffman ML. Management of acute hepatitis B. Clin Liver Dis. 2010; 14(1): 75-91; viii-ix. PubMed

Trépo C, L Y Chan H, Lok A. Hepatitis B virus infection. Lancet. 2014; 384(9959): 2053-63. PubMed

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC). Viral Hepatitis - Hepatitis B Information - Q&As for Health Professionals. Centers for Disease Control and Prevention. Atlanta, GA [Last updated Aug 2016; Accessed: Aug 2017]

References from the ARUP Institute for Clinical and Experimental Pathology®

Konnick EQ, Erali M, Ashwood ER, Hillyard DR. Evaluation of the COBAS amplicor HBV monitor assay and comparison with the ultrasensitive HBV hybrid capture 2 assay for quantification of hepatitis B virus DNA. J Clin Microbiol. 2005; 43(2): 596-603. PubMed

La'ulu SL, Roberts WL. The analytic sensitivity and mutant detection capability of six hepatitis B surface antigen assays. Am J Clin Pathol. 2006; 125(5): 748-51. PubMed

Pyne MT, Vest L, Clement J, Lee J, Rosvall JR, Luk K, Rossi M, Cobb B, Hillyard DR. Comparison of three Roche hepatitis B virus viral load assay formats. J Clin Microbiol. 2012; 50(7): 2337-42. PubMed

Medical Reviewers

Last Update: September 2017