Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
Gut Liver. 2017 Sep 15;11(5):590-603. doi: 10.5009/gnl16215.
Nucleos(t)ide analogues (NUCs) and interferon have been used for several decades to treat chronic hepatitis B; however, the therapeutic response remains unsatisfactory. Although NUC therapy exhibits potent on-treatment viral suppression, frequent off-therapy virological relapses suggest an indefinite treatment course. Interferon modulates the innate and adaptive antiviral immune responses and thus increases the chance of viral eradication. Interferon therapy has the advantage of a finite duration, absence of drug resistance, and durable posttreatment responses. Therefore, the combination of NUCs and interferon can theoretically facilitate a synergistic therapeutic effect. This paper summarizes the current strategies of various combination therapies into three categories: the simultaneous "dual" strategy, sequential combination "add-on" strategy, and "switch" strategy. Generally, dual therapy exhibits greater on-treatment and off-therapy viral suppression and lower drug resistance compared with NUC monotherapy. Compared with interferon monotherapy, dual therapy has greater on-treatment viral suppression but shows no difference in off-therapy sustained virological responses. Specific add-on or switch strategies provide promising on-treatment efficacy in select patients. Pretreatment or on-treatment quantitative hepatitis B surface antigen and e antigen are predictive for the treatment efficacy of combination therapy. The optimal schedule of combination regimens and individualized therapy remain to be comprehensively evaluated.
核苷（酸）类似物（NUCs）和干扰素已被用于治疗慢性乙型肝炎数十年；然而，治疗反应仍不尽如人意。尽管 NUC 治疗在治疗期间表现出强大的病毒抑制作用，但频繁的治疗后病毒学复发表明需要无限期的治疗过程。干扰素调节先天和适应性抗病毒免疫反应，从而增加病毒清除的机会。干扰素治疗具有疗程有限、无耐药性和持久的治疗后反应的优势。因此，NUC 和干扰素的联合治疗理论上可以促进协同治疗效果。本文将各种联合治疗策略总结为三类：同时的“双重”策略、序贯联合“附加”策略和“转换”策略。一般来说，双重治疗在治疗期间和治疗后显示出比 NUC 单药治疗更强的病毒抑制作用和更低的耐药性。与干扰素单药治疗相比，双重治疗在治疗期间具有更强的病毒抑制作用，但在治疗后持续病毒学应答方面没有差异。特定的附加或转换策略为选择的患者提供了有前途的治疗效果。治疗前或治疗期间的乙型肝炎表面抗原和 e 抗原定量是联合治疗疗效的预测因素。联合治疗方案的最佳方案和个体化治疗仍需全面评估。
