— Christine M. Kukka, Project Manager, HBV Advocate
When do hepatitis B tests miss true infections?A number of confounding
factors, ranging from "occult" hepatitis B increase (see above
article), failure of lab tests to pick up extremely low levels of HBsAg,
immunizations, and the rapidly changing progression of HBV infection
can all conspire to mask the infection from conventional laboratory
tests.
A recent study by the U.S. Centers for Disease Control and Prevention, published in the August issue of the Journal of Pediatrics,
captures the complexities of hepatitis B testing in the general
population. It examined what happened in pregnant women who initially
tested positive for HBsAg and then weeks later tested negative for the
infection.
All pregnant women in the U.S. are screened for
hepatitis B so doctors can promptly immunize their newborns, within 12
hours of birth, to break the mother-to-child infection cycle and also
so doctors can treat the liver disease in the pregnant women.
Usually these tests only look for HBsAg, but
researchers suggest this can produce an incomplete and inaccurate
picture in people.
- If someone has just been vaccinated with HBsAg,
a blood test would show only the antigens and doctors would assume the
patient was actively infected with HBV. It takes days or weeks for the
immune system to respond to the vaccine and produce antibodies to get
rid of the HBsAg circulating in the bloodstream. But if doctors tested
for both HBsAg and the presence of hepatitis B core antibodies, which
attack the "core" of the virus, they would know the HBsAg resulted from
a chronic infection. The core antibody is present only when someone
has actually been exposed to the real virus and infected.
- There can also be laboratory errors, though the
failure rate of the six available commercial tests for HBsAg now on the
market is not known.
- Occult hepatitis B, that does not produce the
HBsAg that lab tests look for, can also mask an infection and produce a
misleading result. Only if tests for the core antibody and HBV DNA were
included with the HBsAg test would doctors get a 100% accurate
snapshot of someone's infection status if they had occult hepatitis B.
However, current medical guidelines only call for HBsAg testing in
pregnant women.
In the CDC study, researchers examined 142
"discrepant" cases where pregnant women first tested positive for HBsAg
and then tested negative.
- They found that more than half of the cases
(75) were false positives, meaning the women were not actually infected.
The second round of lab tests in the women, which included a core
antibody test, found that 67 of them did not have the core antibody,
and therefore they were not infected.
- In other cases of false positives, the women had
recently been immunized and still had HBsAg circulating in them from
the vaccine.
- In two cases, the false positives were the result of laboratory errors.
- In other cases, patients could have been newly
infected with HBV, but when the second test occurred, they had resolved
their infections and cleared HBsAg from their bodies.
- In addition to occult hepatitis B rendering
inaccurate test results, if women have very low levels of HBsAg, the lab
test often fails to identify the minute levels of HBsAg, according to
the report.
"When results are in that so-called 'gray zone,'
repeat testing of the same or subsequent specimens can result in
discrepancies," CDC researchers noted. Researchers speculated that a
lab could find HBsAg in a woman's first lab test but miss it the next
time because of low HBsAg levels.
HBV genotypes or strains may also play a role in
determining which women fall in this hazardous gray zone. In the CDC
study, Asian-American women, who often have genotype B or C, were
nearly all accurately screened because high viral loads and elevated
HBsAg levels are hallmarks of both genotypes.
In contrast, Hispanic women in the study often had
genotypes A or H. This genotype is associated with lower HBV DNA
levels in women of child-bearing age. Most of the Hispanic women in the
study were from Texas, which requires two HBV tests during pregnancy.
Researchers noted that the doubling up of HBV
testing in pregnant women, as is now done in Texas, could benefit women
by increasing the chance of identifying those with low viral loads who
may have tested negative for HBsAg during the first test.
Also, adding a core antibody test to the current
HBsAg screening would also produce far more accurate results,
researchers noted. CDC experts suggest that to be on the safe side,
immediate immunization of newborns should occur whenever there are
discrepant results in the mother.
Source: www.ncbi.nlm.nih.gov/pubmed/25063719
Source: HBV Journal Review: August 1, 2014, Vol 11, no 8
Labels: diagnostic test accuracy, tests during pregnancy
