HBe Ag (hepatitis B e antigen )

Last reviewed 03/2022

  • hepatitis B "e" antigen (HBeAg) indicates a highly infectious state
  • HBeAg appears within 1 week of HBsAg - in acute cases HBeAg disappears prior to the disappearance of HBsAg
  • HBeAg is only found if HBsAg is also found
  • HBeAg occurs early in disease
    • generally lasts 3-6 weeks
    • if HBeAg persists > 10 weeks then this suggests progression to chonic carrier state and possibly chronic hepatitis

     

Phases of Hepatitis B infection - relates HbeAg and HBV DNA levels

  • immune-tolerance phase
    • the immune-tolerance phase is seen in HBeAg-positive disease and is characterised by high levels of HBV replication with normal ALT levels and limited liver necroinflammation
    • because there is minimal immune response to the virus it is unusual for spontaneous HBeAg loss to occur
    • this phase is commonly seen in children

  • immune-clearance phase
    • followed by an immune-clearance or immune-reactive phase in which the immune system recognises and starts to clear the virus
      • ALT levels are typically elevated or fluctuating, and there is a higher risk of liver fibrosis
      • tends to be the initial phase in people infected with HBV as adults
        • lasts from weeks to years and ends with HBeAg seroconversion

  • immune-control phase
    • with the loss of HBeAg the person may enter an immune-control phase with very low or undetectable HBV DNA levels, normal ALT and minimal fibrosis progression
    • anti-HBe positive

  • immune-escape phase
    • however, some people may experience rising HBV DNA levels despite HBeAg negativity. This is caused by virions that do not express HBeAg because of genetic mutations
      • this immune-escape phase can lead to active necroinflammation and progression of fibrosis
      • anti-HBe positive

Notes:

  • HBeAg seroconversion

    • HBeAg seroconversion occurs when people infected with the HBeAg-positive form of the virus develop antibodies against the 'e' antigen.
      • the seroconverted disease state is referred to as the 'inactive HBV carrier state' when HBeAg has been cleared, anti-HBe is present and HBV DNA is undetectable or less than 2000 IU/ml. Once seroconversion has taken place, most people remain in the inactive HBV carrier state (the immune-control phase)
        • however, increasing HBV DNA and recurrent hepatitis after seroconversion indicate the emergence of the HBeAgnegative strain of the virus (the immune-escape phase). people may experience rising HBV DNA levels despite HBeAg negativity. This is caused by virions that do not express HBeAg because of genetic mutations. This immune-escape phase can lead to active necroinflammation and progression of fibrosis
  • a form of the virus that does not cause infected cells to secrete HBeAg has been discovered (sometimes called the 'precore mutant' strain)

    • people can be infected with the so-called HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in people initially infected with the HBeAg-positive form of the virus
    • prevalence of HBeAg-negative hepatitis varies geographically; it is more common in Asia and the Mediterranean region than in Northern Europe

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