Kumar Rakesh, Agrawal Babita
Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.
Curr Opin Investig Drugs. 2004 Feb;5(2):171-8.
Chronic hepatitis B virus (HBV) infection affects between 350 and 400 million people globally. Interferon-alpha, lamivudine and adefovir (Hepsera) are approved for the treatment of chronic hepatitis B; however, the use of interferon-alpha is limited. Lamivudine and adefovir have excellent antiviral activity and oral bioavailability, although viral rebound after cessation of therapy and development of resistance after long-term therapy with lamivudine are major clinical limitations. Adefovir has proven to be effective against lamivudine-resistant strains in vitro and in vivo. The various steps of HBV replication provide opportunities for new antiviral drugs to interact with the virus. Recent developments, including new antivirals that interfere with viral DNA replication, hold promise for the future. Sustained reduction in viral load and improved treatment of chronic HBV infection could, in future, be achieved by the development of new drugs with different mechanisms of action and resistance profiles, and with combination therapy involving two or more nucleosides with or without immunomodulators.
慢性乙型肝炎病毒（HBV）感染在全球影响着3.5亿至4亿人。α干扰素、拉米夫定和阿德福韦（贺维力）已被批准用于治疗慢性乙型肝炎；然而，α干扰素的使用受到限制。拉米夫定和阿德福韦具有出色的抗病毒活性和口服生物利用度，尽管治疗停止后病毒反弹以及长期使用拉米夫定治疗后出现耐药性是主要的临床局限性。阿德福韦已被证明在体外和体内对拉米夫定耐药菌株有效。HBV复制的各个步骤为新型抗病毒药物与病毒相互作用提供了机会。包括干扰病毒DNA复制的新型抗病毒药物在内的近期进展为未来带来了希望。未来，通过开发具有不同作用机制和耐药谱的新药，以及采用涉及两种或更多核苷并伴有或不伴有免疫调节剂的联合疗法，有望实现病毒载量的持续降低以及慢性HBV感染的更好治疗。
