Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
Division of Medical Science of Regional Cooperation for Liver Diseases, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
Int J Mol Sci. 2021 Feb 1;22(3):1456. doi: 10.3390/ijms22031456.
Seroclearance of hepatitis B surface antigen (HBsAg) ("functional cure") is the optimal endpoint of antiviral therapy for chronic hepatitis B virus (HBV) infection. Currently available anti-HBV therapy includes nucleoside/nucleotide analogs (NAs) and peginterferon-α (Peg-IFNα). Combination of NAs and Peg-IFNα, each with different mechanisms of action, is an attractive approach for treating chronic HBV infection. In earlier studies, compared with monotherapy using IFNα, combination therapy showed greater on-treatment HBV DNA suppression but no difference in the sustained response. However, responses to the combination of non-pegylated IFNα with lamivudine or adefovir were not assessed based on HBsAg quantification but were defined by normal alanine aminotransferase levels, testing negative for hepatitis B e-antigen, and low HBV DNA load over a short term. Here, we reviewed previous reports regarding the effects of combination therapy of entecavir or tenofovir with Peg-IFNα, focusing on long-term reduction in HBsAg levels. Regimens of combination therapy were classified into "simultaneous" combination ("de novo" strategy); "sequential" combination, which involved starting with one therapy followed by the other ("switch-to" strategy); "add-on" combination, which involved adding Peg-IFNα to an ongoing NAs. Some studies have shown promising results, but there is no robust evidence that combination therapy is superior to monotherapy. Large studies are needed to assess the safety and efficacy of combination therapies to increase the rates of HBsAg seroclearance over the long term.
乙肝表面抗原（HBsAg）血清清除（“功能性治愈”）是慢性乙型肝炎病毒（HBV）感染抗病毒治疗的最佳终点。目前可用的抗 HBV 治疗包括核苷（酸）类似物（NAs）和聚乙二醇干扰素-α（Peg-IFNα）。NAs 和 Peg-IFNα 的联合治疗，每种药物具有不同的作用机制，是治疗慢性 HBV 感染的一种有吸引力的方法。在早期研究中，与 IFNα 单药治疗相比，联合治疗显示出更强的治疗期间 HBV DNA 抑制作用，但持续应答方面没有差异。然而，联合非聚乙二醇 IFNα 与拉米夫定或阿德福韦酯的应答并未根据 HBsAg 定量进行评估，而是根据短期的 HBsAg 水平、乙型肝炎 e 抗原检测阴性和低 HBV DNA 载量来定义。在这里，我们回顾了关于恩替卡韦或替诺福韦与 Peg-IFNα 联合治疗的先前报告，重点关注 HBsAg 水平的长期降低。联合治疗方案分为“同时”联合（“从头开始”策略）；“序贯”联合，即先进行一种治疗，然后进行另一种治疗（“转换策略”）；“附加”联合，即在正在进行的 NAs 治疗中添加 Peg-IFNα。一些研究显示出有希望的结果，但没有强有力的证据表明联合治疗优于单药治疗。需要进行大型研究来评估联合治疗的安全性和疗效，以提高长期 HBsAg 血清清除率。
