新英格兰医学杂志：乙肝病毒感染药物治疗学

but approximately 1% of persons infected, affects clearance of the infection.5,6,8



Figure 2. Clinical and Epidemiologic Correlations in HBV Infection.

The clinical expression of HBV infection depends on the time of life when the infection is acquired. In Asian countries with a high prevalence of HBV infection, HBV is acquired perinatally from infected mothers. It is not accompanied by acute hepatitis, but it results in chronic infection in more than 90% of patients. Later in life, cirrhosis and hepatocellular carcinoma account for up to a 40% lifetime risk of death. In contrast, in Western countries with a low prevalence of HBV infection, HBV is rarely acquired perinatally but instead is acquired during adolescence and early adulthood; infections acquired in adulthood usually cause a clinically apparent acute hepatitis, but progression to chronic hepatitis is rare, as is the risk of hepatocellular carcinoma.

Immunologic tolerance to HBV established during perinatal infection is profound and lifelong, but not complete; a low level of liver injury occurs and accounts for up to a 40% lifetime risk of death from liver disease among men.9 This risk is lower among women.9 A so-called immune-tolerant phase occurs in the early decades of life, with negligible HBV-associated liver injury despite high-level HBV replication. An immune-clearance phase occurs in the later decades of life with active liver disease. This categorization of phases reflects relatively higher immunologic tolerance early and relatively lower tolerance later in the natural history of chronic HBV infection acquired early in life.5,6,10 Such categorization, however, does not explain the presence of substantial liver injury and fibrosis durin

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