Hepatitis B Serology and Antiviral Therapy
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Direct answer
Hepatitis B serology identifies whether a patient has acute infection, chronic infection, past infection or immunity, using HBsAg, anti-HBc and anti-HBs. Chronic hepatitis B is defined by HBsAg persisting for more than six months, and treatment depends on ALT, HBV DNA and the phase of infection rather than HBsAg alone. Entecavir or tenofovir are the usual first-line antivirals.
What you must remember
- HBsAg: The surface antigen; persistence beyond six months defines chronic hepatitis B, and its loss with anti-HBs appearing is the aim of treatment, a functional cure.
- Anti-HBc IgM: Marks acute infection; in the window period it is the only positive marker when HBsAg has become negative.
- Anti-HBc total: Indicates past or current infection, so an isolated positive result matters before immunosuppressive therapy.
- Anti-HBs: A level of 10 mIU/mL or more indicates immunity from vaccination or natural infection.
- HBeAg: A replication marker; its presence means high infectivity, and its loss with anti-HBe appearing marks seroconversion.
- Drugs of choice: Entecavir or tenofovir, which have a high barrier to resistance; lamivudine is avoided because resistance develops quickly.
A stepwise reading of a serology panel
Take a patient who is HBsAg positive for over a decade, HBeAg negative with anti-HBe positive, with HBV DNA below 2,000 IU/mL and a normal ALT.
- Confirm chronicity: HBsAg has persisted beyond six months, which defines chronic hepatitis B.
- Place him in a phase: This is the inactive carrier or HBeAg-negative phase, with low replication and no active inflammation.
- Check fibrosis: Elastography is done, since significant fibrosis or a family history of liver cancer can change the decision.
- Decide on monitoring: In the absence of those features, most guidance favours monitoring ALT and DNA every three to six months rather than treatment.
Now reverse the picture: HBsAg positive, HBeAg positive, DNA high and ALT persistently raised. This is the immune clearance phase of active disease, and treatment is indicated. The difference between the two patients is not HBsAg, which is positive in both, but replication and inflammation.
A third pattern, IgM anti-HBc positive with HBsAg positive, indicates acute hepatitis B, and routine antiviral treatment is generally not started for an acute self-limiting infection.
Where the exam tries to catch you
Serology questions usually hinge on one marker read in the wrong context.
- Trap: Reading IgM anti-HBc in isolation. Correct: IgM anti-HBc with a positive HBsAg means acute infection, while IgM anti-HBc with a negative HBsAg indicates the window period.
- Trap: Reading anti-HBs alone as past infection. Correct: Anti-HBs together with anti-HBc signals past infection, whereas anti-HBs alone signals vaccination.
- Trap: Assuming HBeAg loss equals cure. Correct: HBsAg loss is the functional cure, while HBeAg loss only marks reduced replication. Precore or core promoter mutants can keep DNA high in HBeAg-negative disease, so treatment depends on DNA and ALT.
- Trap: Forgetting the newborn of an HBsAg-positive mother. Correct: The infant needs hepatitis B immunoglobulin and vaccine within 12 hours of birth, and tenofovir may be considered in late pregnancy when maternal viral load is high.
Frequently asked questions
Which serology pattern indicates the window period of hepatitis B?
In the window period, HBsAg has fallen below detection while anti-HBs has not yet appeared, so IgM anti-HBc is the only positive marker. Testing HBsAg alone would miss acute hepatitis B during this phase.
What defines chronic hepatitis B on serology?
Chronic hepatitis B is defined by HBsAg positivity persisting for more than six months, with or without HBeAg. HBV DNA then quantifies replication, which determines whether treatment is needed.
Which antiviral is preferred first-line for chronic hepatitis B?
Entecavir and tenofovir are the preferred first-line nucleos(t)ide analogues for chronic hepatitis B because of their potency and high barrier to resistance. Lamivudine is largely avoided now because resistance develops quickly during therapy.
Why is HBeAg-negative hepatitis B still treated?
HBeAg-negative chronic hepatitis B can still be active, with high HBV DNA due to precore or core promoter mutants. Treatment decisions therefore depend on DNA and ALT rather than HBeAg status alone.
What prophylaxis is given to an infant born to an HBsAg-positive mother?
Infants born to HBsAg-positive mothers receive hepatitis B immunoglobulin plus the vaccine within 12 hours of birth, then complete the vaccine series. Tenofovir in late pregnancy may be added when maternal viral load is high, to reduce transmission to the infant.