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Hepatitis B Surface Antigen

Hepatitis B virus (HBV) is a small double stranded DNA virus composed of an outer envelope containing hepatitis B surface antigen (HBsAg) and an inner nucleocapsid consisting of hepatitis B envelope antigen (HBeAg) and hepatitis B core antigen (HBcAg). The viral core also contains a double stranded DNA genome and DNA polymerase. 

HBV infection can result in both acute and chronic hepatitis. Approximately 90% of adults who are infected will resolve the infection without permanent organ damage, while 10% become carriers and 6% progress to chronic disease.  Infected newborns and children have a much worse outcome. Chronic infection occurs in 90% of infants infected at birth and in 30% of children infected between ages 1 and 5 years.  

After exposure to HBV, there is an incubation period ranging from 45 to 180 days, during which the patient will not exhibit symptoms or positive serologic results. Symptoms, if they appear, usually occur within 4 to 6 weeks after exposure. The most common symptoms include nausea, anorexia, malaise and jaundice.  The stage of the infection can be monitored with tests for HBV antigens and antibodies. 

HBsAg is the first serologic marker, developing between 6 weeks and 6 months following infection, but prior to onset of symptoms. Presence of HBsAg in serum may indicate acute HBV infection, chronic HBV infection, or asymptomatic carrier state. In acute infection, HBsAg usually disappears within 1 to 2 months after onset of symptoms.  HBsAg persists in patients with chronic hepatitis. The significance of a positive test for HBsAg is determined by evaluating it in relationship to the presence or absence of the other HBV markers and the clinical presentation and history of the patient.

Low level reactive results may be false positive. A neutralization assay should be used to determine if the result is a true or false positive. To perform neutralization, an aliquot of patient sample is incubated with antibody to surface antigen. Then the sample is tested for HBsAg and the result is compared to the signal strength of the untreated sample. Decrease in reactivity of greater than 50% after treatment confirms the positive result.

If a weakly positive sample does not neutralize, a few other steps might be taken to determine if the result is a true positive for HBsAg. 

  • Repeat the test after recentrifugation to remove fibrinogen
  • Repeat the test using EDTA plasma instead of serum.
  • Repeat the test using a different method
  • Determine if the patient was recently vaccinated for hepatitis B

In some cases, a patient with a low reactive HBsAg test might have a mutant viral strain that escapes detection by certain assays. A person may have been originally been infected by a mutant strain or the mutation could have occurred during antiviral therapy. Mutant strains should be considered when a patient has any of the following results are obtained:

  • HBsAg positive, HBsAb positive
  • HBsAg negative and HBeAg or HBV DNA negative
  • Isolated HBcAb positive
  • Discordant HBsAg results by different assays

Healthy individuals may test positive for HBsAg for up to 18 days after hepatitis B virus vaccination. Because of immunosuppression, hemodialysis patients may test positive up to 52 days after vaccination. This does not mean the person is infected with HBV. 

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