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

HBV is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide, resulting in an estimated 887,000 deaths per year. An estimated 257 million people have chronic HBV infection globally. Although accurate data are lacking from many countries, Map 4-4 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 ≥2%, such as in the western Pacific and African regions; 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 4-4. Prevalence of hepatitis B virus infection
Map 4-4. Prevalence of hepatitis B virus infection

Disease data source: Schweitzer A, Horn J, Mikolajczyk R, Krause G, Ott J. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Jul 28;386(10003):1546–55.

Clinical Presentation

HBV infection primarily affects the liver. Typically, the incubation period for hepatitis B is 90 days (range, 60–150 days). Newly acquired acute HBV infections only cause symptoms some of the time. The presence of signs and symptoms varies by age. Most children under age 5 years and newly infected immunosuppressed adults are generally asymptomatic, whereas 30%–50% of people aged ≥5 years have signs and symptoms. When present, the typical signs and symptoms of acute infection include malaise, fatigue, poor appetite, nausea, vomiting, abdominal pain, fever, dark urine, light color (clay-colored) stool, joint pain, and jaundice. The overall case-fatality ratio of acute hepatitis B is approximately 1%.

Some acute HBV infections will resolve on their own, but some will develop into chronic infection. The risk of acute hepatitis B progressing to chronic HBV infection depends on the age at the time of initial infection as follows: >90% of neonates and infants, 25%–50% of children aged 1–5 years, and <5% of older children and adults. Most people with chronic HBV infection are asymptomatic and have no evidence of liver disease. However, 15%–40% of people with chronic HBV infection will develop liver cirrhosis, hepatocellular carcinoma, or liver failure, and 25% die prematurely of these complications. 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

The clinical diagnosis of acute HBV infection is based on signs or symptoms consistent with viral hepatitis and elevated hepatic transaminases but cannot be distinguished from other causes of acute hepatitis. Serologic markers specific for hepatitis B are necessary to diagnose HBV infection and for appropriate clinical management (Table 4-3). These markers can differentiate between acute, resolving, and chronic infection. Hepatitis B is a nationally notifiable disease.

Table 4-3. Interpretation of serologic test results for hepatitis B virus infection

Clinical state

HBsAg

Total anti-HBs

Total anti-HBc

Action

Chronic infection

Positive

Negative

Positive

Link to hepatitis B-directed care

Acute

Positive

Negative

Positive (IgM anti-HBc)

Link to hepatitis B-directed care

Resolved infection

Negative

Positive

Positive

Counseling, reassurance

Immune (immunization)

Negative

Positive

Negative

Reassurance

Susceptible (never infected and no evidence of immunization)

Negative

Negative

Negative

Vaccinate

Isolated core antibody 1

Negative

Negative

Positive

Depends on situation

Abbreviations: HBsAg, hepatitis B surface antigen; anti-HBc, antibody to hepatitis B core antigen; anti-HBs, antibody to hepatitis B surface antigen; hepatitis B-directed care, physical exam and laboratory evaluation for liver transaminase, HBV DNA, and hepatitis B e antigen.

From: 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(11):794-804.

1 Can be a result of:

  • False positive, repeat testing required.

  • Past infection, no action needed.

  • Occult HBV infection, needs to be known if patient ever becomes immunosuppressed or given chemotherapy or treated with antiviral therapy for hepatitis C virus infection. Consider monitoring HBV DNA.

  • Passive transfer to infant born to HBsAg-positive mother; no specific action needed.

Treatment

There are no medications available to treat acute HBV; treatment is supportive. There are several antiviral medications for people with chronic HBV infection. People with chronic HBV should be under the care of a health professional and receive a thorough physical examination and laboratory testing to determine the need for antiviral therapy and ongoing monitoring for hepatocellular carcinoma and liver damage related to chronic HBV infection. American Association for the Study of Liver Diseases (AASLD) practice guidelines are available for the treatment of chronic HBV infection and can be found at www.aasld.org/publications/practice-guidelines-0.

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/hcp/acip-recs/vacc-specific/hepb.html. Vaccination to prevent hepatitis B should be considered for all international travelers, regardless of destination.

Vaccine Administration

Multiple hepatitis B vaccines are available (Table 4-4). The vaccine is administered either as a 2-dose series on a 0- and 1-month schedule (for Heplisav-B) or a 3-dose series on a 0-, 1-, and 6-month schedule (for Engerix-B, Recombivax HB, and Twinrix). For the 2-dose vaccine, the second dose should be given ≥1 month after the first dose. For 3-dose vaccines, the third dose should be given ≥2 months after the second dose and ≥4 months after the first dose. The third dose of Engerix-B 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 is effective in preventing transmission after exposure to HBV; hepatitis B vaccine alone may also be used if HBIG is not available.

Table 4-4. Vaccines to prevent hepatitis B

Vaccine

Trade Name (Manufacturer)

Age (Y)

Dose

Route

Schedule

Booster

Hepatitis B vaccine, recombinant with novel adjuvant (1018)

Heplisav-B (Dynavax Technologies)

>18

0.5 mL(20 µg HBsAg and 3000 µg of 1018)

IM

0, 1 mo

None

Hepatitis B vaccine, recombinant 1

Engerix-B (GlaxoSmithKline)

0–19 (primary)

0.5 mL (10 µg HBsAg)

IM

0, 1, 6 mo

None

0–10 (accelerated)

0.5 mL (10 µg HBsAg)

IM

0, 1, 2 mo

12 mo

11–19 (accelerated)

1 mL (20 µg HBsAg)

IM

0, 1, 2 mo

12 mo

≥20 (primary)

1 mL (20 µg HBsAg)

IM

0, 1, 6 mo

None

≥20 (accelerated)

1 mL (20 µg HBsAg)

IM

0, 1, 2 mo

12 mo

Hepatitis B vaccine, recombinant 1

Recombivax HB (Merck & Co., Inc.)

0–19 (primary)

0.5 mL (5 µg HBsAg)

IM

0, 1, 6 mo

None

11–15 (adolescent accelerated)

1 mL (10 µg HBsAg)

IM

0, 4–6 mo

None

≥20 (primary)

1 mL (10 µg HBsAg)

IM

0, 1, 6 mo

None

Combined hepatitis A and B vaccine

Twinrix (GlaxoSmithKline)

≥18 (primary)

1 mL (720 ELU HAV + 20 µg HBsAg)

IM

0, 1, 6 mo

None

≥18 (accelerated)

1 mL (720 ELU HAV + 20 µg HBsAg)

IM

0, 7, 21–30 d

12 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.

Heplisav-B (Dynavax Technologies Corporation) is licensed for a 2-dose schedule for adults aged ≥18 years; 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). A combined hepatitis A and hepatitis B vaccine (Twinrix) can also be used on a 3-dose schedule (0, 7, and 21–30 days), with a booster at 12 months. The prescribing information should always be consulted when administering alternate schedules and formulations. Whenever feasible, the same manufacturer’s vaccines should be used to complete the series; however, vaccination should not be deferred when the manufacturer of previously administered doses is unknown or when the vaccine from the same manufacturer is unavailable. The 2-dose Heplisav-B vaccine series only applies when both doses in the series consist of Heplisav-B. Series consisting of a combination of 1 dose of Heplisav-B and a vaccine from a different manufacturer should adhere to the 3-dose schedule. Protection from the primary vaccination series is robust, and >95% of healthy people achieve immunity after completion of the vaccine series. Serologic testing and booster vaccination are not recommended before travel for immunocompetent adults who have been previously vaccinated.

Special Situations

Ideally, vaccination with Heplisav-B should begin ≥1 month before travel so the full vaccine series can be completed before departure. When vaccines other than Heplisav-B are used, vaccination should begin ≥6 months before travel. 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 vaccine series is completed, 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 for the combined hepatitis A and hepatitis B vaccine, Twinrix, 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. Alternatively, Heplisav-B may be used as a 2-dose series at 0 and 4 weeks to protect against hepatitis B alone.

Vaccine Safety and Adverse Reactions

There are safe hepatitis B vaccines available for people of all ages, and adverse reactions are rare. The most common adverse reactions are soreness at the injection site (3%–29%) and low-grade fever (temperature >99.9°F [37.7°C]; 1%–6%). 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 and contains an adjuvant (either aluminum [for Engerix-B, Recombivax HB, Twinrix] or 1018 [small synthetic immunostimulatory cytidine-phosphate-guanosine oligodeoxynucleotide motif for Heplisav-B]).

Limited data indicate no apparent risk of adverse events to the mother or the developing fetus when licensed 3-dose series hepatitis B vaccine is administered to pregnant women. There are no data on use of 2-dose series vaccines (Heplisav-B) in 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 use of licensed 3-dose series hepatitis B vaccines.

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 advised against 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. 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(11):794–804.  [PMID:29159414]
  2. CDC. Updated US Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for post-exposure prophylaxis. MMWR Recomm Rep. 2001 Jun 29;50(RR-11):1–42.
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  5. 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 Recomm Rep 2018;67(15);455–8.
  6. Schillie S, Vellozzi C, Reingold A, Harris A, Haber P, Ward JW, et al. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2018 Jan 12;67(RR-1):1–31.  [PMID:29939980]
  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

Aaron M. Harris