The clinical outcome of HBV is a result of a combination of the level of replication attained by the virus and the nature of the patient’s immune response.
Patients with persistent hepatitis B generally exhibit one of four major clinical patterns of infection:
1. Profound immunotolerance and mild hepatitis B despite high levels of replication of the virus (HBeAg-positive immunotolerant chronic hepatitis B).
2. Active infection (sustained high levels of replication of HBV and raised ALT) in which the ‘wild-type’ HBeAg-positive HBV is predominant (chronic HBeAg-positive hepatitis B).
3. Active infections in which variant forms of HBV unable to secrete HBeAg are predominant (chronic HBeAg-negative or ‘precore mutant’ chronic hepatitis B).
4. Inactive HBV infection (HBeAg-negative inactive disease).
A fifth profile, of uncertain clinical significance, is occult HBV infection which is characterised by the persistence of HBV DNA in liver tissue in HBsAgnegative patients.
It is important to note that these phases are by no means static and can change from one to the other.
The virological pattern of chronic hepatitis B is changing in many parts of the world. A few decades ago the disease was characterised primarily by wild-type (HBeAg-positive chronic hepatitis B) infection. In recent years the prevalence of HBeAg-positive relative to HBeAg-negative infection has diminished. A substantial proportion of HBV infection is now characterised by HBV variants unable to secrete HBeAg.