Serological Markers of HBV Infection

8/10/2019 Serological Markers of HBV Infection

1/8

Serological markers of HBV infection

During HBV infection, the serological markers vary depending onwhether the infection is acute or chronic.11, 23, 31

Antigens Antibodies

HBsAg

Hepatitis B surface antigen is the earliestindicator of acute infection and is alsoindicative of chronic infection if its presencepersists for more than 6 months. It is usefulfor the diagnosis of HBV infection and forscreening of blood.

Its specific antibody is anti-HBs.

anti-HBs

This is the specific antibody to hepatitis Bsurface antigen. Its appearance 1 to4 months after onset of symptoms indicatesclinical recovery and subsequent immunity toHBV. Anti-HBs can neutralize HBV andprovide protection against HBV infection.

HBcAg

Hepatitis B core antigen is derived from theprotein envelope that encloses the viralDNA, and it is not detectable in thebloodstream. When HBcAg peptides areexpressed on the surface of hepatocytes,

they induce an immune response that iscrucial for killing infected cells. The HBcAg isa marker of the infectious viral material and itis the most accurate index of viralreplication.

Its specific antibody is anti-HBc.

anti-HBc

This is the specific antibody to hepatitis Bcore antigen. Antibodies to HBc are of classIgM and IgG. They do not neutralize thevirus. The presence of IgM identifies an earlyacute infection. In the absence of HBsAg

and anti-HBs, it shows recent infection. IgGwith no IgM may be present in chronic andresolved infections. Anti-HBc testingidentifies all previously infected persons,including HBV carriers, but does notdifferentiate carriers and non-carriers.


2/8

HBeAg

Hepatitis B e antigen appearing duringweeks 3 to 6 indicates an acute activeinfection at its most infectious period, and

means that the patient is infectious.

Persistence of this virological marker beyond10 weeks shows progression to chronicinfection and infectiousness. Continuouspresence of anti-HBe indicates chronic orchronic active liver disease. HBeAg is notincorporated into virions, but is insteadsecreted into the serum. Mutant strains ofHBV exist that replicate without producingHBeAg. HBeAgs function is uncertain.

Its specific antibody is anti-HBe.

anti-HBe

This is the specific antibody to hepatitis B eantigen. During the acute stage of infectionthe seroconversion from e antigen to e

antibody is prognostic for resolution ofinfection. Its presence in the patients bloodalong with anti-HBc and in the absence ofHBsAg, anti-HBs and core HBV mutantsindicates low contagiousness andconvalescence. 31

HBxAg

Hepatitis B x antigen is detected in HBeAgpositive blood in patients with both acute andchronic hepatitis. HBxAg is a transcriptionalactivator. It does not bind to DNA.

Its specific antibody is anti-HBx.

anti-HBx

This is the specific antibody to hepatitis B xantigen. It appears when other virologicalmarkers are becoming undetectable.

HBV DNA

HBV DNA is detectable by hybridizationassays or PCR as soon as 1 week afterinitial infection. The tests are generallyperformed for monitoring of antiviraltreatment or to detect mutants that escapedetection by current methods.


3/8

HBV DNA polymerase

Tests for the presence of HBV DNApolymerase, detectable within 1 week ofinitial infection, are only performed forresearch purposes.

HBV serological markers in hepatitis patients

The three standard blood tests for hepatitis B can determine if aperson is currently infected with HBV, has recovered, is a chroniccarrier, or is susceptible to HBV infection.15, 23, 31

Assay results

InterpretationHBsAg anti-HBs anti-HBc

+ - - Early acute HBV infection

+ +/- + Acute or chronic HBV infection.Differentiate with IgM-anti-HBc

. Determine level of infectivity with

HBeAg or HBV DNA.

Indicates previous HBV infection and


4/8

- + + immunity to hepatitis B.

- - + Possibilities include: past HBV infection;low-level HBV carrier; time spanbetween disappearance of HBsAg andappearance of anti-HBs; or false-positive or nonspecific reaction.Investigate with IgM anti-HBc, and/orchallenge with HBsAg vaccine. Whenpresent, anti-HBe helps validate the

anti-HBc reactivity.

- - - Another infectious agent, toxic injury tothe liver, disorder of immunity,hereditary disease of the liver, or

disease of the biliary tract.

- + - vaccine-type response.

From: Hollinger FB, Liang TJ. Hepatitis B Virus. In: Knipe DM et al., eds. FieldsVirology, 4th ed., Philadelphia, Lippincott Williams &Wilkins, 2001:2971-3036,15with permission (http://lww.com).

Interpretation of HBV serologic markers in patients with hepatitis.15


5/8

Serological test findings at different stages of HBV infection and inconvalescence

anti-HBc

Stage of infection HBsAg anti-HBs IgG

IgM HBeAg

anti-HBe

late incubationperiod

+ - - - + or - -

acute hepatitis B orpersistent carrierstate

+ - + + + -

HBsAg-negativeacute hepatitis Binfection

- - - + - -

recovery with lossof detectable anti-HBs

- - + - - -

healthy HBsAg ++


6/8

carrier + - + + or - - +

chronic hepatitis B,persistent carrierstate

+ - +++

+ or - + -

HBV infection inrecent past,convalescence

- ++ ++ + or - - +

HBV infection indistant past,recovery

- + or - +or-

- - -

recent HBVvaccination,

repeated exposureto antigen withoutinfection, orrecovery frominfection with lossof detectable anti-HBc

- ++ - - - -


7/8

From: Robinson WS. Hepatitis B virus and hepatitis D virus. In: Mandell GL,Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 4 thed.New York, Churchill Livingstone, 1995:1406-1439,31with permission.

Discordant or unusual hepatitis B serological profiles requiringfurther evaluation

Repeat testing of the same sample or possibly of an additional sampleis advisable when tests yield discordant or unusual results.15

HBsAg positive / anti-HBcnegative

An HBsAg-positive response is accompaniedby an anti-HBc negative reaction only duringthe incubation period of acute hepatitis B,before the onset of clinical symptoms andliver abnormalities.

HBsAg positive / anti-HBspositive / anti-HBc positive

Uncommon, may occur during resolution ofacute hepatitis B, in chronic carriers whohave serious liver disease, or in carriersexposed to heterologous subtypes of HBsAg.

anti-HBcpositive only Past infection not resolved completely

HBeAg positive / HBsAgnegative

Unusual


8/8

HBeAg positive / anti-HBepositive

Unusual

anti-HBs positive only in anonimmunized person

It may be a result of passive transfer of anti-HBs after transfusion of blood from a

vaccinated donor, in patients receivingclotting factors, after IG administration, or innewborn children of mothers with recent orpast HBV infection.

Passively acquired antibodies disappeargradually over 3 to 6 months, whereasactively produced antibodies are stable overmany years.

Apparently quite common when person hasforgotten his/her immunization status!

Mutant proteins from mutant HBV strains may escape diagnosticdetection. The presence of different serological markers shouldtherefore be tested for a correct diagnosis. Diagnostic kits shouldcontain antibodies against a variety of mutant proteins, if perfection isthe goal.

Serological Markers of HBV Infection

Documents

Transcript of Serological Markers of HBV Infection