Borgia G, Gentile I
Department of Public Medicine and Social Security, Section of Infectious Diseases, Center for Basic and Clinical Immunology Research, CISI, University of Naples Federico II, via S. Pansini, 5, I-80131 Naples, Italy.
Curr Med Chem. 2006;13(23):2839-55. doi: 10.2174/092986706778521995.
Three hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15-40% of these subjects will develop cirrhosis, liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade thanks to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. However, these agents have increased the complexity of the management of hepatitis B. Five drugs have been approved for chronic hepatitis B treatment: standard interferon-alpha 2b, pegylated interferon-alpha 2a, lamivudine, adefovir dipivoxil, and entecavir. A definite course of standard or pegylated interferon is administered to induce hepatitis B virus clearance. Unfortunately, these agents are not effective in all patients and are associated with not negligible side effects. Nucleoside or nucleotide analogues that inhibit hepatitis B virus polymerase induce on-treatment suppression of viral replication but patients tend to relapse after cessation of treatment. Consequently, these analogues, which are well tolerated, should be used for prolonged periods, even indefinitely. However, prolonged treatment is associated with a high rate of resistance. The following anti-hepatitis B virus drugs are currently undergoing clinical testing: telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine and thymosin-+/-1. Here we will examine the mechanism of action, efficacy, safety, tolerability and emergence of resistance of agents used to treat chronic hepatitis B. We shall also examine the potential of drugs now being tested and of combination treatment.
据估计，全球有3.5亿人长期感染乙肝病毒。其中15%至40%的患者在其一生中会发展为肝硬化、肝衰竭或肝细胞癌。在过去十年中，由于核苷/核苷酸类似物的出现以及聚乙二醇化干扰素的使用，慢性乙型肝炎的治疗取得了显著进展。然而，这些药物增加了乙肝治疗管理的复杂性。有五种药物已被批准用于慢性乙型肝炎的治疗：标准干扰素-α 2b、聚乙二醇化干扰素-α 2a、拉米夫定、阿德福韦酯和恩替卡韦。给予标准或聚乙二醇化干扰素的明确疗程以诱导乙肝病毒清除。不幸的是，这些药物并非对所有患者都有效，且伴有不可忽视的副作用。抑制乙肝病毒聚合酶的核苷或核苷酸类似物可在治疗期间抑制病毒复制，但患者在停药后往往会复发。因此，这些耐受性良好的类似物应长期使用，甚至无限期使用。然而，长期治疗会导致高耐药率。以下抗乙肝病毒药物目前正在进行临床试验：替比夫定、恩曲他滨、富马酸替诺福韦二吡呋酯、克来夫定和胸腺肽α1。在此，我们将研究用于治疗慢性乙型肝炎的药物的作用机制、疗效、安全性、耐受性和耐药性的出现。我们还将研究目前正在测试的药物以及联合治疗的潜力。
