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Summary and Introduction
Summary
In high endemic areas of hepatitis B virus (HBV) infection, the vast majority of infection is acquired perinatally or during early childhood. The age of the patient is, therefore, almost equivalent to the duration of HBV infection. The natural history of chronic HBV infection consists of three chronological phases: immune tolerance, immune clearance and low replicative phases. The prevalence of hepatitis B e antigen (HBeAg) in asymptomatic HBV carriers is around 90% before 15 years of age, and decreases remarkably to less than 10% after 40 years of age. The immune clearance phase is characterized by a series of hepatitis flares and remissions. These will be followed eventually by HBeAg seroconversion, which is usually accompanied by remission of liver disease and confers favourable outcome. However, patients with persistent HBeAg seropositivity over 40 years of age are associated with a significantly higher risk for progression to cirrhosis than those with HBeAg seroconversion before 40 years of age, and thus should be considered as patients with 'delayed' HBeAg seroconversion. Antiviral or immunomodulatory therapy should be considered seriously for these patients.
Introduction
Chronic hepatitis B virus (HBV) infection is a global public health problem. It is estimated that 350 million persons in the world are chronic carriers of HBV and 75% of them reside in Asia-Pacific region. Of these chronic infected individuals, more than 150 000 die annually of hepatitis B-associated liver disease. The prognosis of chronic HBV infection is determined by the status of viral replication and by the degree of histological liver damage. Although the epidemiological characteristics, clinical features and natural history of chronic HBV infection vary in different geographical areas, it is universal that hepatitis B e antigen (HBeAg) seroconversion is an important event with favourable outcomes, although untoward sequelae may still occur after HBeAg seroconversion in some patients. In addition, the increasing Asian immigrants to the western or developed countries have made chronic HBV infection acquired perinatally or during early childhood a global health issue.
Recent studies, mostly in patients with chronic HBV infection acquired perinatally or during early childhood, have identified several factors associated with the progression of liver disease. These factors include viral load, viral genotypes, viral mutants and age of HBeAg seroconversion. For the latter, it was demonstrated that the risk increases with increasing age. There was a hint in an early study from Taiwan that persistent HBeAg positivity over 40 years of age was associated with an increased risk of active cirrhosis. However, the duration of HBeAg positivity that was associated with increased risk for progression of liver disease has not been defined. In this paper, we review the natural history and pathogenesis of chronic HBV infection acquired at early infancy, with special emphasis on the impact of age on HBeAg seroconversion. We aim to define 'delayed' HBeAg seroconversion or the age of persistent HBeAg seropositivity for which antiviral or immunomodulatory therapy should be considered more seriously.
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