新英格兰医学杂志：乙肝病毒感染药物治疗学

sed circular DNA (cccDNA) becomes established in hepatocyte nuclei and HBV DNA becomes integrated into the host genome (Figure 1).



Figure 1. Steps of HBV Replication.

The hepatitis B virus (HBV) establishes covalently closed circular DNA (cccDNA) as a durable miniature chromosome in the host nucleus and relies on a retroviral strategy of reverse transcription from RNA to negative-strand DNA. The steps of HBV replication targeted by nucleoside and nucleotide analogues that are used to treat chronic HBV infection are shown. ER denotes endoplasmic reticulum, and HBsAg hepatitis B surface antigen.

Progression from acute to chronic HBV infection is influenced by the patient's age at acquisition of the virus; age is also related to a dichotomy in the clinical expression of HBV infection between high-prevalence (e.g., Asian) and low-prevalence (e.g., Western) countries (Figure 2). In the Far East, where HBV infection is acquired perinatally, the immune system does not recognize a difference between the virus and the host, and high-level immunologic tolerance ensues. The cellular immune responses to hepatocyte-membrane HBV proteins that are associated with acute hepatitis do not occur, and chronic, usually lifelong infection is established in more than 90% of persons who are infected. In contrast, in the West, most acute HBV infections occur during adolescence and early adulthood because of behaviors and environments that favor the transmission of bloodborne infections, such as sexual activity, injection-drug use, and occupational exposure. In immunocompetent adults, a strong cellular immune response to "foreign" HBV proteins expressed by hepatocytes results in clinically apparent acute hepatitis, which, in all

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