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Lesson 11. Hepatitis B

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References

  • Abara WE, Qaseem A, Schillie S, McMahon BJ, Harris AM. Hepatitis B Vaccination, Screening, and Linkage to Care: Best Practice Advice From the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2017;167:794-804.
  • Alter HJ, Purcell RH, Gerin JL, et al. Transmission of hepatitis B to chimpanzees by hepatitis B surface antigen-positive saliva and semen. Infect Immun. 1977;16:928-33.
  • Busch K, Thimme R. Natural history of chronic hepatitis B virus infection. Med Microbiol Immunol. 2015;204:5-10.
  • Colin JF, Cazals-Hatem D, Loriot MA, et al. Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology. 1999;29:1306-10.
  • Davis LG, Weber DJ, Lemon SM. Horizontal transmission of hepatitis B virus. Lancet. 1989;1:889-93.
  • Dionne-Odom J, Tita AT, Silverman NS. #38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol. 2016;214:6-14.
  • Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004;350:1118-29.
  • Gupta I, Ratho RK. Immunogenicity and safety of two schedules of Hepatitis B vaccination during pregnancy. J Obstet Gynaecol Res. 2003;29:84-6.
  • Halperin SA, Dobson S, McNeil S, et al. Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults. Vaccine. 2006;24:20-6.
  • Halperin SA, Ward B, Cooper C, et al. Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age. Vaccine. 2012;30:2556-63.
  • Halperin SA, Ward BJ, Dionne M, et al. Immunogenicity of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in nonresponders to licensed hepatitis B vaccine. Hum Vaccin Immunother. 2013;9:1438-44.
  • Heyward WL, Kyle M, Blumenau J, et al. Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared to a licensed hepatitis B vaccine in healthy adults 40-70 years of age. Vaccine. 2013;31:5300-5.
  • Hyams KC. Risks of chronicity following acute hepatitis B virus infection: a review. Clin Infect Dis. 1995;20:992-1000.
  • Jackson S, Lentino J, Kopp J, et al. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Vaccine. 2018;36:668-674.
  • Jourdain G, Ngo-Giang-Huong N, Harrison L, et al. Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B. N Engl J Med. 2018;378:911-23.
  • Launay O, van der Vliet D, Rosenberg AR, et al. Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized controlled trial. JAMA. 2011;305:1432-40.
  • 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;150:874-6.
  • Lu PJ, Byrd KK, Murphy TV, Weinbaum C. Hepatitis B vaccination coverage among high-risk adults 18-49 years, U.S., 2009. Vaccine. 2011;29:7049-57.
  • Mast EE, Weinbaum CM, Fiore AE, et al. 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;55:1-33; quiz CE1-4.
  • Owens DK, Davidson KW, Krist AH, et al. Screening for Hepatitis B Virus Infection in Pregnant Women: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2019;322:349-54.
  • Pan CQ, Duan Z, Dai E, et al. Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load. N Engl J Med. 2016;374:2324-34.
  • Poovorawan Y, Chongsrisawat V, Theamboonlers A, Crasta PD, Messier M, Hardt K. Long-term anti-HBs antibody persistence following infant vaccination against hepatitis B and evaluation of anamnestic response: a 20-year follow-up study in Thailand. Hum Vaccin Immunother. 2013;9:1679-84.
  • Poovorawan Y, Chongsrisawat V, Theamboonlers A, Leroux-Roels G, Crasta PD, Hardt K. Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers. Hum Vaccin Immunother. 2012;8:896-904.
  • Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455-8.
  • Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
  • Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
  • Spradling PR, Xing J, Williams R, et al. Immunity to hepatitis B virus (HBV) infection two decades after implementation of universal infant HBV vaccination: association of detectable residual antibodies and response to a single HBV challenge dose. Clin Vaccine Immunol. 2013;20:559-61.
  • Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-1599.
  • Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014;384:2053-63.
  • Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. Viral hepatitis infections: hepatitis B virus (HBV) infection. MMWR Recomm Rep. 2021;70(No. RR-4):1-187.
  • Wu T, Kwok RM, Tran TT. Isolated anti-HBc: The Relevance of Hepatitis B Core Antibody-A Review of New Issues. Am J Gastroenterol. 2017;112:1780-8.
  • Zanetti AR, Van Damme P, Shouval D. The global impact of vaccination against hepatitis B: a historical overview. Vaccine. 2008;26:6266-73.

Tables

Table 1.

Global Prevalence of Chronic HBV Infection, by Country
Prevalence Category Country

High
(≥8%)

 Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Congo, Côte d’Ivoire, Djibouti, Equatorial Guinea, Gabon, Gambia, Ghana, Guinea, Haiti, Kiribati, Kyrgyzstan, Laos, Liberia, Malawi, Mali, Mauritania, Mongolia, Mozambique, Namibia, Nauru, Niger, Nigeria, Niue, Papua New Guinea, Senegal, Sierra Leone, Solomon Islands, Somalia, South Sudan, Sudan, Swaziland, Togo, Tonga, Uganda, Vanuatu, Vietnam, Yemen, and Zimbabwe.
Intermediate
(5.0-7.9%)		 Albania, Bhutan, Cape Verde, China, Democratic Republic of the Congo, Ethiopia, Kazakhstan, Kenya, Marshall Islands, Moldova, Oman, Romania, Rwanda, Samoa, South Africa, Tajikistan, Tanzania, Thailand, Tunisia, Tuvalu, Uzbekistan, and Zambia.
Low Intermediate
(2.0-4.9%)		 Algeria, Azerbaijan, Bangladesh, Belarus, Belize, Brunei Darussalam, Bulgaria, Cambodia, Colombia, Cyprus, Dominican Republic, Ecuador, Eritrea, Federated States of Micronesia, Fiji, Georgia, Italy, Jamaica, Kosovo, Libya, Madagascar, Myanmar, New Zealand, Pakistan, Palau, Philippines, Peru, Russia, Saudi Arabia, Singapore, South Korea, Sri Lanka, Suriname, Syria, Tahiti, and Turkey.
Low
(≤1.9%)		 Afghanistan, Argentina, Australia, Austria, Bahrain, Barbados, Belgium, Bolivia, Bosnia and Herzegovina, Brazil, Canada, Chile, Costa Rica, Croatia, Cuba, Czech Republic, Denmark, Egypt, France, Germany, Greece, Guatemala, Hungary, Iceland, India, Indonesia, Iran, Iraq, Ireland, Israel, Japan, Jordan, Kuwait, Lebanon, Lithuania, Malaysia, Mexico, Morocco, Nepal, Netherlands, Nicaragua, Norway, Palestine, Panama, Poland, Portugal, Qatar, Serbia, Seychelles, Slovakia, Slovenia, Spain, Sweden, Switzerland, Ukraine, United Kingdom, United Arab Emirates, United States of America, and Venezuela.

No data

 Andorra, Antigua and Barbuda, Armenia, The Bahamas, Botswana, Chad, Comoros, Cook Islands, Dominica, El Salvador, Finland, Grenada, Guinea- Bissau, Guyana, Honduras, Latvia, Lesotho, Lithuania, Luxembourg, Macedonia, Maldives, Malta, Mauritius, Monaco, Montenegro, North Korea, Paraguay, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, San Marino, Sao Tome and Principe, Timor-Leste, Trinidad and Tobago, Turkmenistan, and Uruguay.
NOTE: This table is based on data from the Travelers’ Health Branch of the Centers for Disease Control and Prevention (CDC) Division of Global Migration and Quarantine.the Centers for Disease Control and Prevention (CDC)
Source:
  • Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31. [PubMed Abstract]
Table 2.

Baseline HBV Serologic Results
HBsAg anti-HBs anti-HBc Interpretation Recommended Action
(+) (-) (+) Chronic HBV infection Link to care for HBV treatment
(+) (-) IgM (+) Acute HBV infection Link to care for management and follow-up
(-) (+) (+) Resolved HBV infection Reassurance
(-) (+) (-) Immune to HBV Reassurance
(-) (-) (-) Susceptible to HBV (non immune) Vaccinate
(-) (-) (+)

"Isolated anti-HBc" may represent (1) prior HBV infection, (2) a false-positive test, (3) occult HBV infection, or (4) window phase of acute HBV infection

 Expert consultation advised to determing optional further evaluation and management. 
Abbreviations: HBV= hepatitis B Virus; HbsAg = hepatitis B surface antigen; anti-HBs = hepatitis B surface antibody; anti-HBc = hepatitis B core antibody
Table 3.

Indications for Hepatitis B Vaccination
Groups with Indication for Hepatitis B Vaccination
All infants
Unvaccinated Children Younger than 19 Years of Age

Persons at Risk for HBV Infection by Sexual Exposure

  • Sex partners of HBsAg–positive persons
  • Sexually active persons who are not in a long-term, mutually monogamous relationship (e.g. persons with more than one sex partner during the previous 6 months)
  • Persons seeking evaluation or treatment for a sexually transmitted infection
  • Men who have sex with men

Persons at Risk for Infection by Percutaneous Exposure

  • Persons who currently or recently injected drugs
  • Household contacts of HBsAg-positive persons
  • Residents and staff of facilities for developmentally disabled persons
  • Health care and public safety personnel with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids
  • Hemodialysis, predialysis, peritoneal dialysis, and home dialysis patients
  • Persons with diabetes aged 19-59 years of age
  • Persons with diabetes 60 years of age and older at the discretion of the treating clinician

Others at Increased Risk of Acquiring HBV Infection

  • International travelers to countries with high or intermediate levels of endemic HBV infection (HBsAg prevalence of 2% or greater)
  • Persons with hepatitis C virus infection
  • Persons with chronic liver disease (including, but not limited to, persons with cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an ALT or AST level greater than twice the upper limit of normal)
  • Persons with HIV infection
  • Incarcerated persons
Persons Desiring Protection Against HBV

Abbreviations: ACIP = Advisory Committee on Immunization Practices; HBsAg: hepatitis B surface antigen; HBV = hepatitis B virus; ALT = alanine aminotransferase; AST = aspartate aminotransferase
Source:
  • Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31. [PubMed Abstract]
Table 4.

Interpretation of Test Results for Hepatitis B Virus Infection
HBsAg Total anti-HBc IgM anti-HBc Anti-HBs HBV DNA Interpretation
- - - - - Never infected; susceptible 
+ - - - + or - Early acute infection, or
Transient (up to 18 days) after vaccination
+ + + - + Acute infection
- + + + or - + or - Acute resolving infection
- + - + - Recovered from past infection and immune
+ + - - + Chronic infection
- + - - + or -

Isolated core antibody

False-positive (susceptible), or
Past infection (resolved), or 
“low-level” chronic infection (unlikely to be infectious), or
Passive transfer of anti-HBc to infant born to HBsAg-positive mother
- - - + - Immune if anti-HBs concentration is 10 mIU/mL or greater after completing vaccine series, or
Passive transfer after hepatitis B immune globulin administration (for 3 to 6 months)
Abbreviations: anti-HBc = antibody to hepatitis B core antigen; anti-HBs = antibody to hepatitis B surface antigen; HBsAg = hepatitis B surface antigen; HBV DNA = hepatitis B virus deoxyribonucleic acid; IgM = immunoglobulin class M.
Source:
  • Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31. [PubMed Abstract]
Table 5.

Interpretation of Test Results for Hepatitis B Virus Infection
HBsAg Anti-HBc Anti-HBs Interpretation
Negative Negative Negative Never infected; susceptible 
Positive Negative Negative Early acute infection, or
Transient (up to 18 days) after vaccination
Negative Positive Positive Recovered from past infection and immune
Positive Positive Negative Chronic infection
Negative Positive Negative

Isolated core antibody

  • Past infection (resolved), or
  • False-positive (susceptible), or
  • “Low-level” chronic infection (unlikely to be infectious), or
  • Passive transfer of anti-HBc to infant born to HBsAg-positive mother
Negative Negative Positive Immune if anti-HBs concentration is 10 mIU/mL or greater after completing the vaccine series, or
Passive transfer after hepatitis B immune globulin administration (for 3 to 6 months)
Abbreviations: anti-HBc = antibody to hepatitis B core antigen; anti-HBs = antibody to hepatitis B surface antigen; HBsAg = hepatitis B surface antigen.
Source:
  • Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31. [PubMed Abstract]
Table 6.

Postexposure Management of Health Care Personnel after Occupational Exposure to HBV
  Postexposure Testing Postexposure Prophylaxis  
HCP Status Source Patient (HBsAg) HCP testing (anti-HBs) HBIG Vaccination Postvaccination serologic testing
Documented responder after completing series (≥3 doses) No action needed
Documented nonresponder after two complete series Positive/unknown Not indicated HBIG x 2 separated by 1 month __ N/A
Negative  No action needed
Response unknown after complete series Positive/unknown <10 mIU/mL HBIG x 1 Initiate revaccination Yes
Negative <10 mIU/mL None Initiate revaccination Yes
Any result ≥10 mIU/mL No action needed
Unvaccinated/incompletely vaccinated or persons who refuse HBV vaccine Positive/unknown Not indicated HBIG x 1 Complete vaccination Yes
Negative Not indicated None Complete vaccination Yes

Abbreviations: HCP = health care personnel; HBsAg = hepatitis B surface antigen; anti-HBs = antibody to hepatitis B surface antigen; HBIG = hepatitis B immune globulin; N/A = not applicable.
Source:
  • Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31. [PubMed Abstract]

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