Natural history of chronic hepatitis B virus infection

phase

HBeAg serological status

pattern

indications for treatment

1. “Immune tolerant”

HBeAg positive

• stage seen in many HBeAg-positive children and young adults, particularly among those infected at birth
• high levels of HBV replication (HBV DNA levels >200 000 IU/mL))
• persistently normal ALT
• minimal histological disease

treatment not generally indicated, but monitoring required

2. “Immune active” (HBeAg-positive chronic hepatitis)

HBeAg positive; may develop anti-HBe

• abnormal or intermittently abnormal ALT
• high or fluctuating levels of HBV replication (HBV DNA levels >2000 IU/mL)
• histological necroinflammatory activity present
• HBeAg to anti-HBeseroconversion possible, with normalisation of ALT leading to “immune-control” phase

treatment may be indicated

3. Inactive chronic hepatitis “Immune control” (previously called inactive carrier)

HBeAg negative, anti-HBe positive

• persistently normal ALT
• low or undetectable HBV DNA (HBV DNA levels >2000 IU/mL)
• risk of cirrhosis and HCC reduced
• may develop HBeAg-negative disease

treatment not generally indicated, but monitoring required for reactivation and HCC

4. “Immune escape” (HBeAg-negative chronic hepatitis)

HBeAg negative, with or without being anti-HBe positive

• HBeAg negative and anti-HBe positive
• abnormal ALT (persistent or intermittently abnormal)
• moderate to high levels of HBV replication (HBV DNA levels >20,000 IU/mL)
• older persons especially at risk for progressive disease (fibrosis/cirrhosis)

5.“Reactivation” or “acute-onchronic hepatitis”

HBeAg positive or negative

• can occur spontaneously or be precipitated by immunosuppression from chemo- or immunosuppressive therapy, HIV infection or transplantation, development of antiviral resistance, or withdrawal of antiviral therapy
• abnormal ALT
• moderate to high levels of HBV replication
• seroconversion to HBeAg positivity can occur if HBeAg negative
• high risk of decompensation in presence of cirrhosis

treatment indicated