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Hepatitis A (HAV)   (RNA virus)           hepatitisA_exposure2007.pdf         

REF:   (MMWR May 19, 2006 / 55(RR07);1-23)                              

Hepatitis A virus (HAV), the most common cause of viral hepatitis worldwide, is an RNA virus transmitted exclusively by the fecal-oral route.

Its prevalence is as high as 95% in underdeveloped countries with poor sanitary conditions. The prevalence is >50% in persons older than 50 years in the United States, Canada, and Europe but falls to less than 10% in persons younger than 20 years. Therefore, many persons traveling to endemic regions do not have natural immunity and should receive passive immunization with immunoglobulin before travel.

Signs and Symptoms:
(Ref: Dambro: Griffith's 5-Minute Clinical Consult, 1999)
Fever (60%); unusual with HBV and HCV
Malaise (67%), Fatigue (major complaint in HCV)
Nausea (80%) ,Vomiting, Anorexia (54%)
Jaundice (in adults, 62%); 66% of HCV anicteric
Dark urine (84%)
Abdominal pain (56%)
Meningismus (occasional)

Diagnosis:   (MMWR May 19, 2006 / 55(RR07);1-23)

The presence of active HAV infection is detected by a positive IgM anti-HAV antibody; the presence of the IgG antibody indicates previous infection and immunity.

Hepatitis A cannot be differentiated from other types of viral hepatitis on the basis of clinical or epidemiologic features alone. Serologic testing to detect immunoglobulin M (IgM) antibody to the capsid proteins of HAV (IgM anti-HAV) is required to confirm a diagnosis of acute HAV infection. In the majority of persons, serum IgM anti-HAV becomes detectable 5--10 days before onset of symptoms. IgG anti-HAV, which appears early in the course of infection, remains detectable for the person's lifetime and provides lifelong protection against the disease.

Two serologic tests are licensed for the detection of antibodies to HAV:

  1. IgM anti-HAV and
  2. Total anti-HAV (i.e., IgM and IgG anti-HAV, referred to in this report as anti-HAV).

In the majority of patients, IgM anti-HAV declines to undetectable levels <6 months after infection). However, persons who test positive for IgM anti-HAV >1 year after infection have been reported, as have likely false-positive tests in persons without evidence of recent HAV infection. Total anti-HAV testing is used in epidemiologic studies to measure the prevalence of previous infection or by clinicians to determine whether a person with an indication for pre-exposure prophylaxis is already immune.

HAV RNA can be detected in the blood and stool of the majority of persons during the acute phase of infection by using nucleic acid amplification methods, and nucleic acid sequencing has been used to determine the relatedness of HAV isolates for epidemiologic investigations (28--30). However, only a limited number of research laboratories have the capacity to use these methods.

(Supportive measures are the only treatment necessary in most cases of acute HAV infection.)
Rest and balanced diet
Symptomatic relief medications
Family members: hepatitis evaluation & passive immunization with immunoglobulin 0.02 mL/kg IM
Serial follow up of liver function tests
In patients with severe cholestasis, a short course of prednisolone (30 mg/day with a taper) may reduce the severity of symptoms such as pruritus and malaise and reduce the serum bilirubin level.

Natural History
HAV is typically a benign, self-limited infection, with the majority of patients
exhibiting complete recovery within 2 months of the disease onset. A small subset
of patients will experience symptoms for more prolonged periods of time or have
the relapsing variant. Fulminant hepatitis A is rare.  Chronic HAV disease has not been reported, although rarely individuals may have prolonged relapsing courses or may develop cholestasis during recovery.


Active Immunization: Hepatitis A Vaccine x 2 doses about 6-12 months apart.
A single dose of a highly purified, formalin-inactivated hepatitis A vaccine
is highly protective against HAV. A booster dose is required 6-18 months later for full immunity

Passive Immunication (prophylaxis or post-exposure prophylaxis to Hepatitis A:
Pooled human Immune Serum Immuno Globulin (ISIG) 0.02 mL/kg single IM dose
is recommended for travelers to endemic areas or for household & sexual contacts with serologically confirmed hepatitis A person, to be administered as soon as possible within 2 weeks of exposure.  The duration of protection appears to be dose related, with the 0.02 mL/kg dose providing protection for approximately 3 months and a 0.05 mL/kg dose providing protection for 4 to 6 months.

Prophylaxis Against Hepatitis A Virus Infection

Immune Globulin

IG is a sterile preparation of concentrated antibodies (immunoglobulins) provides protection against hepatitis A through passive transfer of antibody.

When administered for preexposure prophylaxis, 1 dose of 0.02 mL/kg IM confers protection for <3 months, and 1 dose of 0.06 mL/kg IM confers protection for 3--5 months (Table 1). When administered within 2 weeks after an exposure to HAV (0.02 mL/kg IM), IG is 80%--90% effective in preventing hepatitis A. Efficacy is greatest when IG is administered early in the incubation period; when administered later in the incubation period, IG might only attenuate the clinical expression of HAV infection (112).

For administration of IG, an appropriate muscle mass (i.e., the deltoid or gluteal muscle) should be chosen into which a substantial volume can be injected, using a needle length appropriate for the person's age and size. If a gluteal muscle is used, the central region of the buttock should be avoided; only the upper outer quadrant should be used, and the needle should be directed anteriorly to minimize the possibility of injury to the sciatic nerve.

Serious adverse events from IG are rare. Anaphylaxis has been reported after repeated administration to persons with known immunoglobulin A (IgA) deficiency; thus, IG should not be administered to these persons.  Pregnancy or lactation is not a contraindication to IG administration.

IG does not interfere with the immune response to oral poliovirus vaccine or yellow fever vaccine, or, in general, to inactivated vaccines. However, IG can interfere with the response to other live, attenuated vaccines (e.g., measles, mumps, and rubella [MMR] vaccine and varicella vaccine) when administered either as individual or combination vaccines. Administration of MMR should be delayed for >3 months and varicella vaccine for >5 months after administration of IG for hepatitis A prophylaxis. IG should not be administered <2 weeks after administration of MMR or <3 weeks after varicella vaccine unless the benefits of IG administration exceed the benefits of vaccination. If IG is administered <2 weeks after administration of MMR or <3 weeks after administration of varicella vaccine, the person should be revaccinated, but not sooner than 3 months after IG administration for MMR or 5 months for varicella vaccine.

Hepatitis A Vaccine  -  The vaccine should be administered intramuscularly into the deltoid muscle.  

Only vaccines made from inactivated HAV have been evaluated for efficacy in controlled clinical trials . The vaccines containing HAV antigen that are currently licensed in the United States are the single-antigen vaccines HAVRIX® (by GlaxoSmithKline) and VAQTA® (by Merck & Co.) and the combination vaccine TWINRIX® (containing both HAV and HBV antigens; by GlaxoSmithKline). All are inactivated vaccines.

VAQTA is licensed in two formulations, which differ according to the person's age.

HAVRIX is available in two formulations, which differ according to the person's age:

TWINRIX is licensed for use in persons aged >18 years. TWINRIX is a combined hepatitis A and hepatitis B vaccine containing 720 EL.U. of hepatitis A antigen (half of the HAVRIX adult dose) and 20 mcg of recombinant hepatitis B surface antigen protein (the same as the ENGERIX-B adult dose).

Primary immunization consists of 3 doses, administered on a 0-, 1-, and 6-month schedule, the same schedule as that commonly used for single-antigen hepatitis B vaccine. After 3 doses of TWINRIX, antibody responses to both antigens are equivalent to responses seen after the single-antigen vaccines are administered separately on standard schedules).

Persons Traveling to or Working in Countries That Have High or Intermediate Endemicity of Infection

All susceptible persons traveling to or working in countries that have high or intermediate hepatitis A endemicity (Figure 4) should be vaccinated or receive IG before departure. Hepatitis A vaccination at the age-appropriate dose is preferred. Prevaccination testing should be considered for older travelers or for younger persons in certain population groups.

Travelers to Australia, Canada, western Europe, Japan, or New Zealand (i.e., countries in which endemicity is low) are at no greater risk for infection than persons in the United States. Data are not available regarding the risk for hepatitis A for persons traveling to certain areas of the Caribbean, although vaccine or IG should be considered if travel to areas that have questionable sanitation is anticipated.

The first dose of hepatitis A vaccine should be administered as soon as travel is considered. Travelers who are administered vaccine can be assumed to be protected within 4 weeks after receiving the first vaccine dose. Persons administered single-antigen hepatitis A vaccine often will have detectable anti-HAV by 2 weeks after the first vaccine dose; the proportion of persons who will have detectable anti-HAV at 2 weeks might be lower when lower vaccine dosages are used (e.g., in TWINRIX). However, no data are available regarding the risk for hepatitis A among persons vaccinated 2--4 weeks before departure. Because protection might not be complete until 4 weeks after vaccination, for optimal protection, persons traveling to an area in which risk is high <4 weeks after the initial dose also may be administered IG (0.02 mL/kg), but at a different anatomic injection site. Travelers departing in <4 weeks who do not or cannot receive IG should nonetheless receive hepatitis A vaccine and be informed that they might not be optimally protected from acquiring hepatitis A in the immediate future (i.e., subsequent 2--4 weeks). Completion of the vaccine series according to the licensed schedule (Tables 2--4) is necessary for long-term protection.

Travelers who are allergic to a vaccine component or who elect not to receive vaccine should receive a single dose of IG (0.02 mL/kg), which provides effective protection against hepatitis A for up to 3 months (Table 1). Travelers whose travel period is >2 months should be administered IG at 0.06 mL/kg; administration must be repeated if the travel period is >5 months

Postexposure Prophylaxis with IG

Persons who have been recently exposed to HAV and who have not previously received hepatitis A vaccine should be administered a single dose of IG (0.02 mL/kg) as soon as possible. Efficacy when administered >2 weeks after exposure has not been established. Persons who have been administered 1 dose of hepatitis A vaccine at >1 month before exposure to HAV do not need IG.

Because hepatitis A cannot be reliably diagnosed on clinical presentation alone, serologic confirmation of HAV infection in index patients by IgM anti-HAV testing is recommended before postexposure treatment of contacts. Screening of contacts for immunity before administering IG is not recommended because screening would result in delay.

If hepatitis A vaccine is recommended for a person being administered IG (e.g., a person with a recent exposure but also an indication for vaccination), it may be administered simultaneously with IG at a separate anatomic injection site. Unlike IG, hepatitis A vaccine is not licensed for use as postexposure prophylaxis. The completion of studies comparing IG with hepatitis A vaccine for postexposure prophylaxis is needed before vaccine can be recommended in this setting. IG should be administered to previously unvaccinated persons in the following situations.

Close Personal Contact

IG should be administered to all previously unvaccinated household and sexual contacts of persons with serologically confirmed hepatitis A. In addition, persons who have shared illicit drugs with a person who has serologically confirmed hepatitis A should receive IG and hepatitis A vaccine. Consideration should also be given to providing IG to persons with other types of ongoing, close personal contact with a person with hepatitis A (e.g., regular babysitting).

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Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, Sixth Edition,  1998
Dambro: Griffith's 5-Minute Clinical Consult, 1999
ACP Library on Disk 2- (c) 1997 - American College of Physicians