Phases of hepatitis B infection - relating HBe antigen, HBV DNA levels and antibody to HBe antigen

• 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

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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

Reference:

• 1) NICE (June 2013). Hepatitis B (chronic) Diagnosis and management of chronic hepatitis B in children, young people and adults
• 2) NICE (February 2006). Adefovir dipivoxil and peginterferon alfa-2a for the treatment of chronic hepatitis B