Discovery of the hepatitis B virus (HBV) earned Baruch
Blumberg, MD, PhD, the Nobel Prize in 1976 and opened an exciting era of
research that yielded breakthrough tests for HBV that are widely used
today in blood-donor screening and patient diagnosis and management.
Through the years, as knowledge about the virus increased, scientists
identified several distinct diagnostic markers for HBV that allow
clinicians to diagnose and stage the infection and assess immunity.
Although immunization programs have significantly
reduced the incidence of HBV in the United States, the prevalence of
chronic HBV infection remains high. Estimates for the number of
chronically infected individuals in the United States are as high as 1.4
million to 2 million.1,2 Worldwide, 350 million people are
chronically infected with HBV, and about a third of the world's
population has a current or past infection.3
Recently, the U.S. Centers for Disease Control and
Prevention (CDC) and the European Association for the Study of the Liver
(EASL) convened expert panels to update and expand their respective
previous recommendations for identification and public-health management
of persons with chronic hepatitis B infection.1,3 The factors
prompting these revisions included the changing epidemiology of chronic
HBV; the potential for serious liver disease among chronically infected
persons from endemic areas who were infected as infants or children; and
the availability of improved antiviral therapies. Coinciding with World
Hepatitis Day earlier this year, the new CDC recommendations were
discussed by Dr. John Ward, director of the Division of Viral Hepatitis
at the CDC, and co-author of the CDC recommendations published in MMWR.4
In his remarks, Dr. Ward explained that a significant
epidemiological influence in the United States has been increasing
immigration of individuals from areas of the world with
intermediate-to-high prevalence of HBV infection. In a high-prevalence
area, 8% or more of the population is positive for HBV and intermediate
prevalence is defined as 2% to 7% positivity.1 Between
one-third and two-thirds of chronically infected people are unaware of
their infection.4
Testing these individuals and other risk groups
identified by the CDC is critical to diagnose active disease, prevent
ongoing transmission of HBV, offer vaccination to close contacts,
provide antiviral therapy, and prevent later onset of cirrhosis or liver
cancer. Some 15% to 25% of persons with chronic HBV die from HBV-related
cirrhosis and liver cancer.1
In addition to individuals from regions of
high-and-intermediate endemicity, the CDC also added new recommendations
for HBV testing in unvaccinated persons born in the United States whose
parents are from areas of high HBV endemicity, injection-drug users, men
who have sex with men (MSM), and persons taking immunosuppressive drugs
for treatment of cancer and other diseases or to prevent rejection of
transplanted organs.1
As in previous recommendations, the CDC advises using
tests for hepatitis B surface antigen (HBsAg), antibody to HBsAg
(anti-HBs), and antibody to hepatitis B core antigen (anti-HBc) to
evaluate persons for current or past HBV infection. Combinations of
these tests are recommended for use in various at-risk populations.
These assays are widely available in laboratories nationwide on
automated immunoassay systems.
HBsAg is the outer envelope protein of the virus and
is a marker of acute or chronic infection. Anti-HBs indicates recovery
and immunity from a resolved infection or immunity through vaccination,
and anti-HBc is a marker of current or past infection. In persons with
resolved infection, HBsAg becomes undetectable while anti-HBs and anti-HBc
remain for life. In some resolved infections, however, anti-HBs levels
may wane over time, leaving anti-HBc as the only indicator of past
infection. Anti-HBc may also be the only detectable serologic marker in
some chronic infections in which the level of HBsAg is too low to be
detected by current commercially available assays.
An intriguing facet of HBV is its potential to
persist in the liver for many years after apparent recovery from
infection.5 Anti-HBc is an important marker in these cases
and might be the only detectable serologic indicator of past infection.
The expanded CDC recommendations note there is a risk of reactivation in
persons with resolved HBV infection who receive immunosuppressive
therapy for other medical conditions. They also recommend that persons
who are anti-HBc positive should be monitored closely for signs of liver
disease. This patient group includes persons receiving chemotherapy,
immunosuppression related to organ transplantation, and
immunosuppression for rheumatologic or gastroenterologic disorders.
Armed with these recommendations, public-health
organizations and healthcare professionals can direct their outreach
efforts to educate and motivate the expanded at-risk populations to get
tested for HBV and help reduce the consequences of this serious disease.
References
- Weinbaum CM, Williams I, Mast EE, et al.
Recommendations for identification and public health management of
persons with chronic hepatitis B virus infection. MMWR.
2008;57(RR08):1-20. - Gish RG, Gadano AC. Chronic hepatitis B: current
epidemiology in the Americas and implications for management. JViral
Hepatitis. 2006;13:787-798. - European Association for the Study of the Liver.
EASL clinical practice guidelines: management of chronic hepatitis B.
JHepato. 2009;50:227-242. - Ward J. “Improving Diagnosis of Chronic Hepatitis
B: Updated CDC Guidelines on Populations Recommended for Testing and
Specific Testing Considerations,” educational webcast sponsored by
Abbott Diagnostics. May 19, 2009. - Marusawa H, Uemoto S, Hijikata M, et al. Latent
hepatitis B virus infection in healthy individuals with antibodies to
hepatitis B core antigen. Hepatology. 2000;31 (2):488-495.
Mary C. Kuhns, PhD, RM(NRCM), M(ASCP)CM,
is a Volwiler Research Fellow and manager of infectious diseases in the
global scientific affairs group at Abbott Diagnostics in Abbott Park,
IL. Dr. Kuhns received her doctorate in microbiology and developmental
biology from Ohio State University and completed her post-doctoral
training in genetics at Yale University School of Medicine. She has
published extensively on immunoassays and nucleic-acid testing in
hepatitis diagnostics.
