Hepatitis B

Infectious Agent

Hepatitis B virus (HBV), a small, circular, partially double-stranded DNA virus in the family Hepadnaviridae.

Transmission

HBV is transmitted by contact with contaminated blood, blood products, and other body fluids (such as semen). Examples of exposures associated with transmission that travelers may encounter include poor infection control during medical or dental procedures, receipt of blood products, injection drug use, tattooing or acupuncture, and unprotected sex.

Epidemiology

An estimated 248 million people have chronic HBV infection globally. Although accurate data are lacking from many countries, Map 3-4 shows the estimated prevalence of chronic HBV infection by country. No data are available to show the specific risk to travelers; however, published reports of travelers acquiring hepatitis B are rare, and the risk for travelers who do not have high-risk behaviors or exposures is low. The risk for HBV infection may be higher in countries where the prevalence of chronic HBV infection is high or intermediate; expatriates, missionaries, and long-term development workers may be at increased risk for HBV infection in such countries. All travelers should be aware of how HBV is transmitted and take measures to minimize their exposures.

Map 3-4. Prevalence of hepatitis B virus infection 1
Descriptive text is not available for this image

1 Disease data source: Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott J. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. The Lancet. 2015 Jul 28; 386(10003):1546–1555.

Clinical Presentation

HBV infection primarily affects the liver. Typically, the incubation period for hepatitis B is 90 days (range, 60–150 days). The typical signs and symptoms of acute infection include malaise, fatigue, anorexia, nausea, vomiting, abdominal pain, and jaundice. In some cases, skin rashes, joint pain, and arthritis may occur. Among people aged ≥5 years, 30%–50% will develop signs and symptoms. In children aged <5 years and immunocompromised adults, HBV infection is typically asymptomatic, but it can be asymptomatic at any age among healthy people. The overall case-fatality ratio of acute hepatitis B is approximately 1%.

Acute hepatitis B progresses to chronic HBV infection in 30%–90% of people infected as infants or young children and in <5% of people infected during adolescence or adulthood. Chronic infection with HBV may result in chronic liver disease, including cirrhosis, liver cancer, and death. People infected with HBV are susceptible to infection with hepatitis D virus; coinfection increases the risk of fulminant hepatitis and rapidly progressive liver disease.

Diagnosis

Serologic markers specific for hepatitis B are necessary to diagnose HBV infection and to identify the stage of infection (Table 3-3). These markers can differentiate between acute, resolving, and chronic infection. Hepatitis B is a nationally notifiable disease.

Table 3-3. Interpretation of serologic test results for hepatitis B virus infection 1
Serologic MarkerInterpretation
HBsAg 2Total anti-HBcIgM anti-HBcAnti-HBs
Never infected
+Early acute infection; transient (≤18 days) after vaccination
+++Acute infection
+++ or –Acute resolving infection
++Recovered from past infection and immune
++Chronic infection
+False positive (susceptible); past infection; occult infection 3; or passive transfer of anti-HBc to infant born to HBsAg-positive mother
+Immune if concentration is ≥10 mIU/mL after vaccine series completion; passive transfer after hepatitis B immune globulin administration
Abbreviations: HBsAg, hepatitis B surface antigen; anti-HBc, antibody to hepatitis B core antigen; anti-HBs, antibody to hepatitis B surface antigen.
1 From: 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 Dec 8;55(RR-16):1–33.
2 To ensure that an HBsAg-positive test result is not a false positive, samples with reactive HBsAg results should be tested with a licensed neutralizing confirmatory test, if recommended in the manufacturer’s prescribing information.
3 People positive only for anti-HBc are unlikely to be infectious except under unusual circumstances in which they are the source for direct percutaneous exposure of susceptible recipients to large quantities of virus (such as blood transfusion or organ transplant).

Treatment

No specific treatment is available for acute hepatitis B; however, supportive treatment, including hospitalization, may be indicated for some people with severe clinical manifestations. Antiviral drugs are approved and available to treat chronic HBV infection and prevent progression of disease.

Prevention

Vaccine

Indications for Use

Hepatitis B vaccination should be administered to all unvaccinated people traveling to areas with intermediate to high prevalence of chronic HBV infection (HBV surface antigen prevalence ≥2%). Complete vaccination information and recommendations for the United States are available at www.cdc.gov/vaccines/vpd-vac/hepb/default.htm. Vaccination to prevent hepatitis B may be considered for all international travelers, regardless of destination, depending on the traveler’s behavioral risk. However, the vaccine should be considered for all nonimmune travelers since it is often difficult to assess risk during the pretravel consultation or even in the primary care setting.

Vaccine Administration

Hepatitis B vaccine (Table 3-4) is usually administered as a 3-dose series on a 0-, 1-, 6-month schedule to achieve immunity. The second dose should be given ≥1 month after the first dose; the third dose should be given ≥2 months after the second dose and ≥4 months after the first dose. The third dose should not be administered before age 24 weeks. Four doses of hepatitis B vaccine can be administered when a combination vaccine containing hepatitis B is administered after the birth dose. Postexposure prophylaxis with hepatitis B immune globulin (HBIG) administered in conjunction with hepatitis B vaccine, as well as hepatitis B vaccine alone, is effective in preventing transmission after exposure to HBV.

Table 3-4. Vaccines to prevent hepatitis B
VaccineTrade Name (Manufacturer)Age (y)DoseRouteScheduleBooster
Hepatitis B vaccine, recombinant 1Engerix-B (GlaxoSmithKline)0–19 (primary)0.5 mL (10 µg HBsAg)IM0, 1, 6 moNone
0–10 (accelerated)0.5 mL (10 µg HBsAg)IM0, 1, 2 mo12 mo
11–19 (accelerated)1.0 mL (20 µg HBsAg)IM0, 1, 2 mo12 mo
≥20 (primary)1.0 mL (20 µg HBsAg)IM0, 1, 6 moNone
≥20 (accelerated)1.0 mL (20 µg HBsAg)IM0, 1, 2 mo12 mo
Hepatitis B vaccine, recombinant 1Recombivax HB (Merck & Co., Inc.)0–19 (primary)0.5 mL (5 µg HBsAg)IM0, 1, 6 moNone
11–15 (adolescent accelerated)1.0 mL (10 µg HBsAg)IM0, 4–6 moNone
≥20 (primary)1.0 mL (10 µg HBsAg)IM0, 1, 6 moNone
Combined hepatitis A and B vaccineTwinrix (GlaxoSmithKline)≥18 (primary)1.0 mL (720 ELU HAV +  20 μg HBsAg)IM0, 1, 6 moNone
≥18 (accelerated)same as aboveIM0, 7, 21–30 d12 mo
Abbreviations: HBsAg, hepatitis B surface antigen; IM, intramuscular; ELU, ELISA units of inactivated HAV; HAV, hepatitis A virus.
1 Consult the prescribing information for differences in dosing for hemodialysis and other immunocompromised patients.

Exceptions to this schedule are available with specific licensed products in the United States; Recombivax HB (Merck & Co.) is licensed for a 2-dose schedule for children aged 11–15 years, and Engerix-B (GlaxoSmithKline) is licensed for a 4-dose schedule, with the first 3 doses within 2 months and a booster at 12 months (doses at 0, 1, 2, and 12 months). Combination vaccines including hepatitis B are available for children, and a combination hepatitis A and hepatitis B vaccine, Twinrix (GlaxoSmithKline), is also licensed in the United States. Consult the prescribing information when administering alternate schedules and formulations. Vaccination series begun with one brand may be completed with another brand. Protection from the primary vaccination series is robust, and >95% of healthy people achieve immunity with the 3-dose series. Serologic testing and booster vaccination are not recommended before travel for immunocompetent adults who have been previously vaccinated.

Special Situations

Ideally, hepatitis B vaccination should begin ≥6 months before travel so the full vaccine series can be completed before departure. Because some protection is provided by 1 or 2 doses, the vaccine series should be initiated, if indicated, even if it cannot be completed before departure. Optimal protection, however, is not conferred until after the final vaccine dose is received, and travelers should be advised to complete the vaccine series. An approved accelerated vaccination schedule can be used for people traveling on short notice who face imminent exposure or for emergency responders to disaster areas. The accelerated vaccination schedule calls for vaccine doses administered at days 0, 7, and 21–30; a booster should be administered at 12 months to promote long-term immunity. A combined hepatitis A and hepatitis B vaccine can also be used on the same 3-dose schedule (0, 7, and 21–30 days), with a booster at 12 months.

Vaccine Safety and Adverse Reactions

Hepatitis B vaccines are safe for people of all ages. Pain at the injection site (3%–29%) and fever (temperature >99.9°F [37.7°C]; 1%–6%) are the most frequently reported side effects among vaccine recipients. Hepatitis B vaccines should not be administered to people with a history of hypersensitivity to any vaccine component, including yeast. The vaccine contains a recombinant protein (hepatitis B surface antigen) that is noninfectious.

Limited data indicate no apparent risk of adverse events to the mother or the developing fetus when hepatitis B vaccine is administered to pregnant women. HBV infection affecting a pregnant woman can result in serious disease for the mother and chronic infection for the newborn. Neither pregnancy nor lactation should be considered a contraindication for vaccination.

Personal Protection Measures

As part of the pretravel education process, all travelers should be counseled and given information about the risks for hepatitis B and other bloodborne pathogens from contaminated equipment or items used during medical, dental, or cosmetic procedures; blood products; injection drug use; any activities or procedures that involve piercing the skin or mucosa; or unprotected sexual activity. When seeking medical or dental care or cosmetic procedures (such as tattooing or piercing), travelers should be alert to the use of equipment that has not been adequately sterilized or disinfected, reuse of contaminated equipment, and unsafe injecting practices (such as reuse of disposable needles and syringes). HBV and other bloodborne pathogens can be transmitted if tools are not sterile or if personnel do not follow proper infection control procedures. Travelers should consider the health risks when receiving medical or dental care overseas; information may be available from the US embassy. The health risks should be strongly considered when deciding to obtain a tattoo or body piercing in areas where adequate sterilization or disinfection procedures might not be available or practiced.

CDC website: www.cdc.gov/hepatitis/HBV

Bibliography

  1. 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 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005 Dec 23;54(RR-16):1–31.
  2. 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 Dec 8;55(RR-16):1–33.
  3. CDC. Updated US Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2001 Jun 29;50(RR-11):1–42.
  4. Mariano A, Mele A, Tosti ME, Parlato A, Gallo G, Ragni P, et al. Role of beauty treatment in the spread of parenterally transmitted hepatitis viruses in Italy. J Med Virol. 2004 Oct;74(2):216–20.  [PMID:15332269]
  5. Pepin J, Abou Chakra CN, Pepin E, Nault V, Valiquette L. Evolution of the global burden of viral infections from unsafe medical injections, 2000–2010. PLoS One. 2014;9(6):e99677.  [PMID:24911341]
  6. Sagliocca L, Stroffolini T, Amoroso P, Manzillo G, Ferrigno L, Converti F, et al. Risk factors for acute hepatitis B: a case-control study. J Viral Hepat. 1997 Jan;4(1):63–6.  [PMID:9031067]
  7. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386(10003):1546–55.  [PMID:26231459]
  8. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016 Jan;63(1):261–83.  [PMID:26566064]

Author

Francisco Averhoff