Tziomalos Konstantinos
Konstantinos Tziomalos, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki 54636, Greece.
World J Hepatol. 2009 Oct 31;1(1):43-7. doi: 10.4254/wjh.v1.i1.43.
Chronic hepatitis B (CHB) represents an important public health problem. HBeAg-negative CHB is frequently associated with advanced liver disease and its prevalence is increasing. Monotherapy with either interferon (conventional or pegylated) or nucleoside/nucleotide analogues has its limitations. It has been suggested that a combination of these agents might increase antiviral efficacy. However, existing data do not support this hypothesis, even though combination treatment appears to reduce the risk for emergence of lamivudine resistance. Nevertheless, most existing combination studies are small, and it is possible that they have not been designed to detect significant differences between combination treatment and monotherapies. Another limitation of these studies is that, in most of them, lamivudine treatment was discontinued after 1 year, a strategy that is not followed in clinical practice. It was thought to be interesting to evaluate the combination of a short course of interferon (particularly pegylated) with the long-term administration of nucleotide or nucleoside analogues. The efficacy of combining pegylated interferon with the newer nucleotide or nucleoside analogues or of nucleotide with nucleoside analogues could also be evaluated. However, findings show that until more data are available, combination therapy cannot be recommended as first-line treatment in patients with CHB. On the other hand, add-on therapy with adefovir or tenofovir is the treatment of choice in patients who develop resistance to lamivudine. In patients with cirrhosis, a combination of lamivudine/adefovir may also be used as initial treatment; another option would be to add tenofovir in patients with an insufficient response to entecavir.
慢性乙型肝炎（CHB）是一个重要的公共卫生问题。HBeAg阴性慢性乙型肝炎常与晚期肝病相关，且其患病率正在上升。单用干扰素（普通干扰素或聚乙二醇化干扰素）或核苷/核苷酸类似物进行治疗均有其局限性。有人提出，联合使用这些药物可能会提高抗病毒疗效。然而，现有数据并不支持这一假说，尽管联合治疗似乎能降低拉米夫定耐药的发生风险。尽管如此，大多数现有的联合治疗研究规模较小，有可能它们在设计上并未旨在检测联合治疗与单一疗法之间的显著差异。这些研究的另一个局限性在于，在大多数研究中，拉米夫定治疗1年后即停药，而这一策略在临床实践中并未采用。评估短期疗程的干扰素（尤其是聚乙二醇化干扰素）与长期使用核苷酸或核苷类似物联合使用的效果被认为是很有意义的。聚乙二醇化干扰素与新型核苷酸或核苷类似物联合使用的疗效，或者核苷酸与核苷类似物联合使用的疗效也可以进行评估。然而，研究结果表明，在有更多数据可用之前，联合治疗不能被推荐作为慢性乙型肝炎患者的一线治疗方法。另一方面，对于对拉米夫定产生耐药的患者，加用阿德福韦或替诺福韦是首选治疗方法。对于肝硬化患者，拉米夫定/阿德福韦联合治疗也可作为初始治疗；另一种选择是，对于对恩替卡韦反应不足的患者加用替诺福韦。
