Department of Hepatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan,
J Gastroenterol. 2013 Sep;48(9):999-1005. doi: 10.1007/s00535-012-0742-5. Epub 2013 Jan 22.
Currently available antiviral treatment for chronic hepatitis B virus infection can be divided into two classes of therapeutic agents: nucleos(t)ide analogues (NAs) and interferon (IFN). The major advantages of NAs are good tolerance and potent antiviral activity associated with high rates of on-treatment response to therapy; the advantages of IFN include a finite course of treatment, absence of drug resistance, and an opportunity to obtain a post-treatment durable response to therapy. The use of these two antiviral agents with different mechanisms of action in combination is theoretically an attractive approach for treatment. Here, we have reviewed previous reports of either simultaneous or sequential combination therapy with NA and IFN for chronic hepatitis B patients. In previous studies comparing the lamivudine/IFN combination and lamivudine monotherapy in a finite course, combination therapy was associated with higher rates of sustained post-treatment response and lower rates of drug resistance than lamivudine monotherapy. However, NAs such as lamivudine are generally administered indefinitely because of high rates of post-treatment relapse. In addition, concern for drug resistance has decreased significantly with newer, high-potency NAs even when administered alone. In previous studies comparing the lamivudine/IFN combination and IFN monotherapy, the combination therapy showed greater on-treatment viral suppression, but no difference was observed in the post-treatment sustained response. Thus, whether combination therapy confers an additional benefit compared to monotherapy for treating chronic hepatitis B remains unclear. The efficacy of IFN in combination with a more potent NA, such as entecavir or tenofovir, remains to be comprehensively evaluated.
目前，慢性乙型肝炎病毒感染的抗病毒治疗可分为两类治疗药物：核苷（酸）类似物（NAs）和干扰素（IFN）。NAs 的主要优点是良好的耐受性和强效的抗病毒活性，与治疗中的高应答率相关；IFN 的优点包括有限的疗程、无耐药性以及获得治疗后持久应答的机会。这两种具有不同作用机制的抗病毒药物联合使用在理论上是一种有吸引力的治疗方法。在这里，我们回顾了以前关于 NAs 和 IFN 联合治疗慢性乙型肝炎患者的报告。在以前的研究中，比较了拉米夫定/IFN 联合治疗和拉米夫定单药治疗的有限疗程，联合治疗与拉米夫定单药治疗相比，具有更高的持续治疗后应答率和更低的耐药率。然而，由于治疗后复发率高，通常需要无限期使用 NAs，如拉米夫定。此外，即使单独使用，新型高效 NAs 的耐药性问题也得到了显著改善。在以前的研究中，比较了拉米夫定/IFN 联合治疗和 IFN 单药治疗，联合治疗显示出更强的治疗期间病毒抑制，但在治疗后持续应答方面没有差异。因此，与单药治疗相比，联合治疗是否能为慢性乙型肝炎的治疗提供额外的益处仍不清楚。IFN 联合更有效的 NA（如恩替卡韦或替诺福韦）的疗效仍有待全面评估。
