The natural history of hepatitis B virus infection.

It was previously thought that two distinct types of chronic hepatitis B virus (HBV) infection existed. However recent evidence suggests that these are in fact phases in a continuous spectrum which evolves with time. Immediately after infection there is active viral replication. In patients infected in adult life, particularly in Europe and the USA, this is associated with varying degrees of liver damage. In those infected at birth, particularly in the Far East, there is initially much less inflammation with normal liver function. In succeeding years, viral replication decreases and liver damage increases with more deranged liver function test results. Eventually viral replication ceases and liver inflammation decreases, resulting in seroconversion with a loss of HBeAg and appearance of anti-HBe. Unfortunately, cirrhosis has already developed in some adults, with the increased risk of the later development of primary hepatocellular carcinoma. It is likely that there is a favourable window during the natural history of the infection when interferon is effective, probably in the few years immediately before spontaneous seroconversion.