Zoulim Fabien
INSERM Unit 271, Lyon, France.
Drug Saf. 2002;25(7):497-510. doi: 10.2165/00002018-200225070-00004.
Chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Until recently, interferon (IFN)-alpha was the only approved drug for the treatment of chronic HBV infection. The recent registration of lamivudine, a dideoxycytidine analogue that inhibits both the HIV and HBV reverse transcriptases, has provided new perspectives for the treatment of chronic HBV infection. Lamivudine treatment for 12 months leads to a control of viral replication during therapy in the majority of the patients and to sustained anti-hepatitis B e (anti-HBe) seroconversion in 16 to 22% of the patients, associated with a biochemical and histological response. Further studies showed that extended lamivudine therapy increases the rate of anti-HBe seroconversion. However, long-term therapy is associated with the progressive emergence of drug resistant mutants. In most cases these mutants are not associated with a deterioration of the liver disease within the available follow-up. In the remaining patients and in particular settings such as liver transplantation, a severe exacerbation of the liver disease is observed and that requires add-on therapy. Lamivudine treatment of patients infected with a pre-core mutant also showed beneficial effect with the control of viral replication, and a biochemical and histological response in approximately 60% of the patients at 1 year. These patients face the same problem of drug resistant mutants, and the optimal duration of lamivudine treatment still needs to be determined in this clinical situation. Moreover, lamivudine therapy is the only therapeutic option in decompensated cirrhotic patients to allow liver transplantation, and in liver transplant patients with HBV recurrence following transplantation. Adverse effects of lamivudine therapy are comparable to those observed in placebo-treated patients. ALT flares have been observed mainly in relation to the re-occurrence of viral replication due to the rebound of viral replication after therapy withdrawal, or to the emergence of drug resistance mutants. Therefore, lamivudine provides a new treatment alternative for patients with chronic HBV infection. For each patient, its indication has to be weighed against the risk of developing viral resistance but also against the risk of natural history of the disease.
慢性乙型肝炎病毒（HBV）感染仍是全球主要的公共卫生问题。直到最近，α干扰素（IFN）仍是唯一被批准用于治疗慢性HBV感染的药物。拉米夫定（一种抑制HIV和HBV逆转录酶的双脱氧胞苷类似物）最近获批，为慢性HBV感染的治疗提供了新的视角。拉米夫定治疗12个月可使大多数患者在治疗期间的病毒复制得到控制，16%至22%的患者出现持续的抗乙肝e抗原（抗-HBe）血清学转换，并伴有生化和组织学反应。进一步研究表明，延长拉米夫定治疗可提高抗-HBe血清学转换率。然而，长期治疗会导致耐药突变体逐渐出现。在大多数情况下，这些突变体在现有的随访期间与肝病恶化无关。在其余患者中，尤其是在肝移植等情况下，会观察到肝病严重恶化，这需要联合治疗。对感染前核心突变体的患者进行拉米夫定治疗也显示出对病毒复制的控制具有有益效果，约60%的患者在1年时出现生化和组织学反应。这些患者面临同样的耐药突变体问题，在这种临床情况下，拉米夫定治疗的最佳疗程仍有待确定。此外，拉米夫定治疗是失代偿期肝硬化患者进行肝移植以及肝移植后出现HBV复发患者的唯一治疗选择。拉米夫定治疗的不良反应与安慰剂治疗患者中观察到的不良反应相当。ALT升高主要与治疗停药后病毒复制反弹导致的病毒复制再次出现或耐药突变体的出现有关。因此，拉米夫定为慢性HBV感染患者提供了一种新的治疗选择。对于每一位患者，必须权衡其使用指征与出现病毒耐药的风险，同时还要考虑疾病自然史的风险。
