The majority of persons currently treated for chronic hepatitis B require long-term or lifelong therapy. New inhibitors of hepatitis B virus entry, replication, assembly, or secretion and immune modulatory therapies are in development. The introduction of these novel compounds for chronic hepatitis B necessitates a standardised appraisal of the efficacy and safety of these treatments and definitions of new or additional endpoints to inform clinical trials. To move the field forward and to expedite the pathway from discovery to regulatory approval, a workshop with key stakeholders was held in September 2016 to develop a consensus on treatment endpoints to guide the design of clinical trials aimed at hepatitis B cure. The consensus reached was that a complete sterilising cure, i.e., viral eradication from the host, is unlikely to be feasible. Instead, a functional cure characterised by sustained loss of hepatitis B surface antigen with or without hepatitis B surface antibody seroconversion, which is associated with improved clinical outcomes, in a higher proportion of patients than is currently achieved with existing treatments is a feasible goal. Development of standardised assays for novel biomarkers toward better defining hepatitis B virus cure should occur in parallel with development of novel antiviral and immune modulatory therapies such that approval of new treatments can be linked to the approval of new diagnostic assays used to measure efficacy or to predict response. Combination of antiviral and immune modulatory therapies will likely be needed to achieve functional hepatitis B virus cure. Limited proof-of-concept monotherapy studies to evaluate safety and antiviral activity should be conducted prior to proceeding to combination therapies. The safety of any new curative therapies will be paramount given the excellent safety of currently approved nucleos(t)ide analogues.

中文翻译：

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乙肝治愈：从发现到监管批准

目前接受慢性乙型肝炎治疗的大多数人需要长期或终生治疗。乙型肝炎病毒进入、复制、组装或分泌的新抑制剂和免疫调节疗法正在开发中。引入这些用于慢性乙型肝炎的新型化合物需要对这些治疗的有效性和安全性进行标准化评估，并定义新的或额外的终点，以告知临床试验。为了推动该领域向前发展并加快从发现到监管批准的途径，2016 年 9 月与主要利益相关者举行了一次研讨会，以就治疗终点达成共识，以指导旨在治愈乙型肝炎的临床试验的设计。达成的共识是，彻底的绝育治愈，即从宿主中根除病毒，不太可能可行。相反，以乙肝表面抗原持续丢失为特征的功能性治愈是一个可行的目标，即在有或没有乙肝表面抗体血清转化的情况下，在更高比例的患者中改善临床结果，这是一个可行的目标。开发新型生物标志物的标准化检测以更好地定义乙型肝炎病毒治愈应与新型抗病毒和免疫调节疗法的开发同时进行，这样新疗法的批准可以与用于衡量疗效或预测的新诊断检测的批准相关联回复。可能需要结合抗病毒和免疫调节疗法来实现功能性乙型肝炎病毒治愈。在进行联合治疗之前，应进行有限的概念验证单一疗法研究，以评估安全性和抗病毒活性。鉴于目前批准的核苷（酸）类似物的出色安全性，任何新治疗方法的安全性都将是最重要的。