Worldwide more than two billion people have been infected with hepatitis B virus (HBV) and chronic HBV infection affects about 400 million people. It is estimated that more than 500,000 people die annually due to HBVassociated liver disease, largely because of cirrhosis and/or hepatocellular carcinoma. Despite the availability of safe and effective vaccines for more than two decades, HBV infection is still a global health problem.
Background nad significance of the study
In adults, infection with HBV is usually asymptomatic and results in chronic infection in <5% of patients. Infection at younger age is associated with a higher risk of chronic infection, up to 90% in the setting of perinatal transmission. Patients can present with chronic HBV in one of four phases of infection ( figure 1). In the immunotolerant phase of infection, hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) are present and HBV DNA levels are high, >1.0 x 105 copies per millilitre (c/ml). Hepatic inflammation is mild with normal or minimally elevated serum alanine aminotransferase (ALAT) levels and minimal necroinflammation on liver histology. In the immuno-active phase, HBsAg, HBeAg and high HBV DNA are still present, while an active immune response results in hepatic inflammation with elevation of serum ALAT. In the immune-clearance phase HBeAg is present and HBV DNA levels can be high or fluctuating. Liver inflammation is present with elevated serum ALAT and active inflammation on liver histology; loss of HBeAg and seroconversion to anti-HBe can occur. The immune-control stage pursues HBeAg seroconversion. In this phase hepatic inflammation is minimal and HBV DNA levels are low due to continuous host immune response. This phase of infection is also referred to as the 'inactive carrier state'. In an increasing number of patients with HBeAg-negative HBV, biochemical and histological activity recur and HBV DNA levels are high, resulting in HBeAg-negative chronic hepatitis. These patients often originate from the Mediterranean basin, and are infected with hepatitis B variants that hamper the production of HBeAg. The most commonly described mutation is a G to A transition at position 1896 of the precore region. Three major patterns of HBeAg-negative HBV can be distinguished: a recurrent form with exacerbations and periods of remission (45%), an unremitting form (36%), and an unremitting form with acute exacerbations (20%). Despite the occurrence of HBeAg-negative HBV, HBeAg seroconversion is still usually associated with improved long-term outcome and therefore considered an important event in the natural course of chronic HBV.6 Spontaneous HBeAg seroconversion occurs in 8 to 15% of patients in Western countries. Before achieving HBeAg seroconversion many patients have episodes of acute exacerbation. The chance of HBeAg seroconversion during acute exacerbation increases with increasing serum ALAT levels, to 45% in patients with ALAT >5 times the upper limit of normal (ULN).
Significance of the study
Hepatitis B virus (HBV) has influenced more than 2 billion persons worldwide (about one third of the world's community) with more than 350 million persons chronically ...