Rivkin Anastasia
Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, New York, New York, USA.
Drugs Today (Barc). 2007 Apr;43(4):201-20. doi: 10.1358/dot.2007.43.4.1037479.
Infection with hepatitis B virus (HBV) is extremely widespread - it infects two billion people out of the six billion world population. It is estimated that between 350 and 400 million people are chronically infected with HBV. Chronic HBV infection leads to development of complications, such as cirrhosis and hepatocellular carcinoma (HCC), which arise in 15-40% of patients. HBV-related liver disease and its complications result in approximately one million deaths each year. The ultimate goals of chronic hepatitis B (CHB) therapy are decreases in the incidence of cirrhosis, end-stage liver disease and HCC. The following six medications are currently approved by the U.S. Food and Drug Administration for the treatment of CHB: interferon (INF)-alpha2b, pegylated INF-alpha2a, lamivudine, adefovir dipivoxil, entecavir and, recently, telbivudine. Interferon therapy has many contraindications and commonly causes multiple intolerable adverse effects. Lamivudine therapy leads to increased development of resistant mutations with each year of use. Entecavir, a new guanosine nucleoside analogue with specific activity against HBV DNA polymerase, represents a third agent within the nucleoside/nucleotide HBV polymerase inhibitor class. It has distinct advantages over lamivudine and adefovir dipivoxil: it has a three-step mechanism of action, is the most potent inhibitor of HBV DNA polymerase, is not associated with any major adverse effects and has a limited potential for resistance. In clinical trials, entecavir was superior to lamivudine in all primary endpoints in both nucleoside-naive and lamivudine-refractory hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. Preliminary data support entecavir efficacy in patients with cirrhosis and HIV/HBV coinfected patients. No resistance occurred after two years of entecavir therapy in nucleoside-naive patients. Up to 9% resistance developed in patients with documented prior lamivudine resistance during 96 weeks of entecavir therapy. Currently, entecavir should be considered a first- or second-line treatment option for the management of HBeAg-positive or -negative nucleoside-naive or lamivudine-refractory CHB patients.
感染乙肝病毒（HBV）极为普遍——在全球60亿人口中，有20亿人感染过该病毒。据估计，有3.5亿至4亿人长期感染HBV。慢性HBV感染会引发并发症，如肝硬化和肝细胞癌（HCC），15%至40%的患者会出现这些并发症。HBV相关肝病及其并发症每年导致约100万人死亡。慢性乙型肝炎（CHB）治疗的最终目标是降低肝硬化、终末期肝病和HCC的发病率。目前，美国食品药品监督管理局批准了以下六种药物用于治疗CHB：干扰素（INF）-α2b、聚乙二醇化干扰素-α2a、拉米夫定、阿德福韦酯、恩替卡韦，以及最近获批的替比夫定。干扰素治疗有许多禁忌症，且通常会引发多种难以耐受的不良反应。拉米夫定治疗会随着使用年限的增加导致耐药突变的发生率上升。恩替卡韦是一种新型鸟嘌呤核苷类似物，对HBV DNA聚合酶具有特异性活性，是核苷/核苷酸类HBV聚合酶抑制剂中的第三种药物。它相对于拉米夫定和阿德福韦酯具有明显优势：具有三步作用机制，是最强效的HBV DNA聚合酶抑制剂，无任何主要不良反应，耐药可能性有限。在临床试验中，对于初治和拉米夫定耐药的乙肝e抗原（HBeAg）阳性及HBeAg阴性患者，恩替卡韦在所有主要终点方面均优于拉米夫定。初步数据支持恩替卡韦对肝硬化患者及HIV/HBV合并感染患者有效。初治患者接受恩替卡韦治疗两年未出现耐药情况。在接受恩替卡韦治疗96周的既往有拉米夫定耐药记录的患者中，耐药发生率高达9%。目前，恩替卡韦应被视为HBeAg阳性或阴性初治或拉米夫定耐药CHB患者治疗的一线或二线选择。
