Hepatitis A

Infectious Agent

Hepatitis A virus (HAV) is a nonenveloped RNA virus classified as a picornavirus. HAV can survive in the environment for prolonged periods at low pH and in freezing to moderate temperatures.

Transmission

HAV is transmitted through direct person-to-person contact (fecal-oral transmission); contaminated water, ice, or shellfish harvested from sewage-contaminated water; or from contaminated raw, inadequately cooked, or frozen fruits, vegetables, or other foods. HAV is shed in the feces of infected people. People are most infectious 1–2 weeks before the onset of clinical signs and symptoms (jaundice or elevation of liver enzymes), when the concentration of virus is highest in the stool and blood. Viral excretion and the risk of transmission diminish rapidly after liver dysfunction or symptoms appear, which is concurrent with the appearance of circulating antibodies to HAV. Infants and children can shed virus for up to 6 months after infection.

Epidemiology

HAV is common in areas with inadequate sanitation and limited access to clean water. In highly endemic areas (such as parts of Africa and Asia), a large proportion of adults in the population are immune to HAV, and epidemics of hepatitis A are uncommon. In areas of intermediate endemicity (such as Central and South America, Eastern Europe, and parts of Asia), childhood transmission is less frequent, more adolescents and adults are susceptible to infection, and outbreaks are common. In areas of low endemicity (such as the United States and Western Europe), infection is less common, but disease occurs among people in high-risk groups and as communitywide outbreaks.

Hepatitis A is among the most common vaccine-preventable infections acquired during travel. In the United States the most frequently identified risk factors for hepatitis A are international travel and exposure to contaminated food. Cases of travel-related hepatitis A can occur in travelers to developing countries with “standard” tourist itineraries, accommodations, and eating behaviors. Risk is highest for those who live in or visit rural areas, trek in backcountry areas, or frequently eat or drink in settings of poor sanitation. Common source food exposures are increasingly recognized as a risk for hepatitis A, and sporadic outbreaks are reported in Europe, Australia, North America, and other regions with low levels of endemic transmission.

Clinical Presentation

The incubation period averages 28 days (range, 15–50 days). Infection can be asymptomatic or range in severity from a mild illness lasting 1–2 weeks to a severely disabling disease lasting several months. Clinical manifestations include the abrupt onset of fever, malaise, anorexia, nausea, and abdominal discomfort, followed within a few days by jaundice. The likelihood of having symptoms with HAV infection is related to the age of the infected person. In children aged <6 years, most (70%) infections are asymptomatic; jaundice is uncommon in symptomatic young children. Among older children and adults, the illness usually lasts <2 months, although approximately 10%–15% of infected people have prolonged or relapsing symptoms over a 6- to 9-month period. Severe hepatic and extrahepatic complications, including fulminant hepatitis and liver failure, are rare but more common in older adults and people with underlying liver disease. Chronic infection does not occur. The overall case-fatality ratio is 0.3%; however, the ratio is 1.8% among adults aged >50 years.

Diagnosis

HAV cannot be differentiated from other types of viral hepatitis on the basis of clinical or epidemiologic features. Diagnosis requires a positive test for antibody to HAV (anti-HAV) IgM in serum, detectable from 2 weeks before the onset of symptoms to approximately 6 months afterward.

Serologic tests for total anti-HAV (IgG and IgM) are available commercially. A positive total anti-HAV result and a negative IgM anti-HAV result indicate past infection or vaccination and immunity. The presence of serum IgM anti-HAV usually indicates current or recent infection and does not distinguish between immunity from infection and vaccination. Acute hepatitis A is a nationally notifiable disease.

Treatment

Supportive care.

Prevention

Vaccination or immune globulin (IG), food and water precautions, maintaining standards of hygiene and sanitation.

Vaccine

Two monovalent hepatitis A vaccines, Vaqta (Merck & Co, Inc, Whitehouse Station, NJ) and Havrix (GlaxoSmithKline Beecham Biologicals, Rixensart, Belgium), are approved for people ≥12 months of age in a 2-dose series, and a combined hepatitis A and hepatitis B (Twinrix, GlaxoSmithKline) vaccine is approved for people ≥18 years of age in the United States (Table 3-2). The immunogenicity of the combination vaccine is equivalent to that of the monovalent hepatitis A and hepatitis B vaccines when tested after completion of the recommended schedule.

Table 3-2. Vaccines to prevent hepatitis A
VaccineTrade Name (Manufacturer)Age (y)DoseRouteScheduleBooster
Hepatitis A vaccine, inactivatedHavrix (GlaxoSmithKline)1–180.5 mL (720 ELU)IM0, 6–12 moNone
≥191.0 mL (1,440 ELU)IM0, 6–12 moNone
Hepatitis A vaccine, inactivatedVaqta (Merck & Co., Inc.)1–180.5 mL (25 U)IM0, 6–18 moNone
≥191.0 mL (50 U)IM0, 6–18 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: ELU, ELISA units of inactivated HAV; IM, intramuscular; U, units HAV antigen; HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen.

Indications for Use

All susceptible people traveling for any purpose, frequency, or duration to countries with high or intermediate HAV endemicity should be vaccinated or receive IG before departure. Although the Advisory Committee for Immunization Practices recommends hepatitis A vaccination for travelers, published maps may not be the best guide for determining endemicity in developing countries. Prevalence patterns of HAV infection vary among regions within a country, and missing or obsolete data present a challenge. Countries where the prevalence of HAV infection is decreasing have growing numbers of susceptible people and risk for large outbreaks of hepatitis A. In recent years, large outbreaks of hepatitis A were reported in developed countries among people who had been exposed to imported food contaminated with HAV. Taking into account the complexity of interpreting hepatitis A risk maps and potential risk of foodborne hepatitis A in countries with low endemicity, some experts advise people traveling outside the United States to consider hepatitis A vaccination regardless of destination.

Vaccination is recommended for unvaccinated household members and other people who anticipate close personal contact (such as household contacts or regular babysitters) with an international adoptee from a country of high or intermediate endemicity during the 60 days after arrival of the child in the United States. The first dose of the 2-dose hepatitis A vaccine series should be administered as soon as adoption is planned, ideally ≥2 weeks before the arrival of the child (see Chapter 7, International Adoption).

Vaccine Administration

One dose of a monovalent hepatitis A vaccine protects most healthy people aged 1–40 years and should be administered as soon as travel is considered. The monovalent vaccine series should be completed according to the licensed schedule for long-term protection. No data on single-dose hepatitis A vaccine efficacy are available for Twinrix. An alternate, accelerated 4-dose schedule is available for Twinrix; doses can be administered at 0, 7, and 21–30 days, followed by a dose at 12 months.

Hepatitis A vaccine at the age-appropriate dose is preferred to IG for children and adults aged 1–40 years. For optimal protection, adults aged >40 years, immunocompromised people, and people with chronic liver disease or other chronic medical conditions planning to depart to an area in <2 weeks should receive the initial dose of vaccine along with IG (0.02 mL/kg) at a separate injection site.

Travelers who are aged <12 months, are allergic to a vaccine component, or who otherwise elect not to receive vaccine should receive a single dose of IG (0.02 mL/kg), which provides effective protection against HAV infection for up to 3 months. Those who do not receive vaccination and plan to travel for >3 months should receive an IG dose of 0.06 mL/kg, which must be repeated if the duration of travel is >5 months. IG can be repeated every 6 months thereafter if the traveler remains in a high-risk setting, though hepatitis A vaccination should be encouraged if not contraindicated.

Although vaccinating an immune traveler is not contraindicated and does not increase the risk for adverse effects, screening for total anti-HAV before travel can be useful in some circumstances to determine susceptibility and eliminate unnecessary vaccination. Postvaccination testing for serologic response is not indicated.

Other Vaccine Considerations

Using vaccine according to the licensed schedule is preferable. An interrupted series does not need to be restarted. More than 95% of vaccinated people develop levels of anti-HAV that correlate with protection 1 month after the first dose. Given their similar immunogenicity, a series that has been started with one brand of hepatitis A monovalent vaccine may be completed with another brand of monovalent vaccine. For children and adults who complete the primary series, booster doses of vaccine are not recommended.

Vaccine Safety and Adverse Reactions

Among adults, the most frequently reported side effects after hepatitis A vaccination are tenderness or pain at the injection site (56%–67%) and headache (14%–16%). Among children (11–25 months of age), the most common reported side effects are pain or tenderness at the injection site (32%–37%) and redness (21%–29%). No serious adverse events in children or adults have been reported that could be attributed definitively to the vaccine; no increase in serious adverse events has been identified among vaccinated people compared with baseline rates.

Precautions and Contraindications

Hepatitis A–containing vaccines should not be administered to travelers with a history of hypersensitivity to any vaccine component, including neomycin. Twinrix should not be administered to people with a history of hypersensitivity to yeast. The tip caps of prefilled syringes of Havrix and Twinrix and the vial stopper, syringe plunger stopper, and tip caps of Vaqta may contain dry natural rubber, which may cause allergic reactions in latex-sensitive people. Because hepatitis A vaccine consists of inactivated virus and hepatitis B vaccine consists of a recombinant protein, no special precautions are needed for vaccination of immunocompromised travelers. Providers should check precautions and contraindications before administering IG.

Pregnancy

The safety of hepatitis A vaccine for pregnant women has not been determined. However, because hepatitis A vaccine is produced from inactivated HAV, the theoretical risk to either the pregnant woman or the developing fetus is thought to be low. A recent review of the Vaccine Adverse Event Reporting System did not identify any concerning patterns of adverse events in pregnant women or their infants after hepatitis A vaccination (Havrix, Vaqta) or hepatitis A and B combined vaccination (Twinrix) during pregnancy. The risk of vaccination should be weighed against the risk of hepatitis A among female travelers who might be at high risk for exposure to HAV.

Postexposure Prophylaxis

Travelers who are exposed to HAV and who have not received hepatitis A vaccine previously should be administered 1 dose of monovalent hepatitis A vaccine or IG (0.02 mL/kg) as soon as possible, ideally within 2 weeks of exposure. The efficacy of IG or vaccine when administered >2 weeks after exposure has not been established. The relative efficacy of vaccine is comparable to IG for postexposure prophylaxis among people aged 1–40 years.

For healthy people aged 1–40 years, a dose of monovalent hepatitis A vaccine is recommended. For people aged >40 years, IG is preferred, but vaccine can be used if IG is unavailable. IG is recommended for children aged <12 months, people who are immunocompromised, people who have chronic liver disease, and people for whom vaccine is contraindicated. Twinrix is not approved for postexposure prophylaxis. More detailed information can be found in the Advisory Committee on Immunization Practices recommendations at www.cdc.gov/mmwr/preview/mmwrhtml/mm5641a3.htm.

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

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Author

Noele P. Nelson