Hepatitis B Virus - HBV

  • Diagnosis
  • Algorithms
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

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 HBV infection

Laboratory Testing

  • Testing and treatment recommendations (CDC, 2016)
  • Differentiation between acute and chronic hepatitis
    • Acute suspected HBV – screen for HBV core antibody (anti-HBc) IgM, hepatitis A (HAV) IgM, hepatitis C (HCV) antibody, and HBV surface antigen (HBsAg)
      • Confirmed if anti-HBc IgM and HBsAg positive
    • Chronic HBV – HBsAg positive for >6 months
      • Active chronic disease
        • Hepatitis Be antigen (HBeAg) positive, anti-HBe negative, 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
    • If either the surface antigen or DNA test is positive – patient is contagious
  • All patients with chronic HBV should be tested for HCV
  • Acute deterioration in patient with known HBV – test for coinfection/superinfection with hepatitis D (HDV)
  • Liver biopsy (EASL, 2009; Lok [AASLD], 2009)
    • Patients should have evidence of active disease – elevated transaminases and DNA >2000 IU/mL
    • In active disease – results of biopsy may guide therapy
    • Useful in patients where advanced fibrosis not suggested by noninvasive testing

Histology

  • Immunohistochemistry for biopsy material – consider HbsAg or HBcAg

Differential Diagnosis

Screening recommendations for HBV

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

CDC, 2008; Lok [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 every 6 months
    • HBsAg, HBeAg, anti-HBe, anti-HBs, HBV DNA, transaminases
      • May need more frequent monitoring for those in immune-active phase
      • Less frequent monitoring for those in inactive phase

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

Epidemiology

  • Incidence
    • ~30% of world population has been exposed (Trepo, 2014)
      • 350 million – chronically infected
    • Endemic in Asia, sub-Saharan Africa, Pacific Islands, and parts of Latin America
    • U.S. cases have dropped 80% with vaccination
      • Prevalence of chronic disease <2%
  • 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 in 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
  • Infants of HBV-infected mothers
  • HIV infection
  • 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
  • Needlestick
    • 1-6% risk if blood is HBsAg(+)
    • 22-40% risk if blood is HBsAg(+) and HBeAg(+)
  • Hemodialysis
  • Blood transfusion (predominantly in developing countries)

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 of vertical transmission if mother is HBsAg positive
      • 70-90% risk of vertical transmission 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 have higher rate of being 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, right-upper quadrant discomfort
    • 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
      • Cirrhosis may present with jaundice, ascites, splenomegaly, encephalopathy, or variceal bleeding
    • Annual incidence for HCC is <1% for noncirrhotic HBV-infected “carriers” and 2-3% for patients with cirrhosis
    • Annual incidence of cirrhosis is 2-6% for HBeAg-negative and 8-10% for HBeAg positive chronic hepatitis patients

Prevention

  • Vaccination recommended for the following
    • 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

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 HBV surface antigen

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

Hepatitis B Surface Antigen by Immunohistochemistry 2003917
Method: Immunohistochemistry

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Related Tests

Guidelines

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

McHugh JA, Cullison S, Apuzzio J, Block JM, Cohen C, Leong SLing, 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

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. 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

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 Abu-Raja, 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 MReza, 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

Viral Hepatitis - Hepatitis B Information. Centers for Disease Control and Prevention. [Accessed: June 2016]

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: July 2016