Treatment of chronic hepatitis B.
Treatment of chronic hepatitis B.
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DOI：
10.1016/s1473-3099(01)00118-9
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发表时间：
2001-11-01
期刊：
影响因子：
--
通讯作者：
Lai, C L
中科院分区：
文献类型：
--
作者：
Yuen, M F;Lai, C L
本综述更新了慢性乙型肝炎感染的治疗。完全根除乙型肝炎病毒（HBV）是不可能的，因此必须通过是否可以限制长期肝硬化相关并发症来评估治疗效果。我们讨论两大类治疗方法——免疫调节剂（干扰素α、胸腺素α1、治疗性疫苗）和核苷类似物（拉米夫定、阿德福韦、恩替卡韦、恩曲他滨、β-L-2'-脱氧胸苷）。迄今为止，干扰素 α 和拉米夫定是仅有的两种被批准用于治疗慢性乙型肝炎的药物。干扰素 α 的短期结果是 HBeAg 降低约 20-30%。中国患者的疗效低于白人患者，因为他们在儿童早期感染乙型肝炎，因此对乙型肝炎具有免疫耐受性。这种差异在长期随访中得到进一步证实。干扰素α不会影响中国患者肝硬化相关并发症的发生，而在白人患者中，如果干扰素α成功诱导HBeAg消失，长期并发症的发生率就会降低。拉米夫定可深度抑制病毒复制，并实现与干扰素 α 相似的 HBeAg 血清转化率。它对中国人和白人患者同样有效，因为主要的抗病毒机制是通过抑制病毒复制过程中乙型肝炎病毒的逆转录。然而，长期拉米夫定治疗与 HBV 变异、YMDD 变异的出现有关。较新的核苷类似物正在通过体内和体外研究进行广泛研究。两种或三种核苷类似物或免疫调节剂加核苷类似物的联合治疗将是未来慢性乙型肝炎治疗的方向。
This review updates the treatment of chronic hepatitis B infection. Complete eradication of hepatitis B virus (HBV) is not possible, so the efficacy of treatment has to be assessed by whether it can limit long-term cirrhosis-related complications. We discuss two major groups of treatments--immunomodulators (interferon alfa, thymosin alpha1, therapeutic vaccines) and nucleoside analogues (lamivudine, adefovir, entecavir, emtricitabine, beta-L-2'-deoxythymidine). To date, interferon alfa and lamivudine are the only two agents approved for chronic hepatitis B. Interferon alfa achieves a short-term outcome of around 20-30% loss of HBeAg. The efficacy is lower in Chinese patients, who are immunotolerant to HBV because of acquisition of the disease during early childhood, than in white patients. This difference is further confirmed on long-term follow-up. Interferon alfa does not affect the development of cirrhosis-related complications in Chinese patients, whereas in white patients, the frequency of long-term complications is reduced if interferon alfa is successful in inducing loss of HBeAg. Lamivudine profoundly suppresses viral replication and achieves an HBeAg seroconversion rate similar to that of interferon alfa. It is equally effective in Chinese and white patients because the main antiviral mechanism is through inhibition of reverse transcription of HBV during viral replication. However, long-term lamivudine therapy is associated with emergence of HBV variants, YMDD variants. Newer nucleoside analogues are being extensively investigated by studies in vivo and in vitro. Combination therapy with two or three nucleoside analogues or immunomodulators plus nucleoside analogues will be the future direction of treatment of chronic hepatitis B.