Emery Joel S, Feld Jordan J
Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Best Pract Res Clin Gastroenterol. 2017 Jun;31(3):347-355. doi: 10.1016/j.bpg.2017.04.007. Epub 2017 May 4.
Chronic Hepatitis B continues as a significant public health problem despite the availability of safe and effective antivirals and a highly effective protective vaccine. Current therapy, however rarely leads to cure and lifelong therapy is often required, contributing to poor uptake and ongoing morbidity. New insights into the hepatitis B viral life cycle and the host immune response have expanded the potential targets for drug therapies with interesting antiviral candidates and novel immunotherapeutic approaches in early stage development. Yet, HBV persistence is multifactorial - due to an intrahepatic reservoir and ongoing HBV-mediated immune dysregulation, making "cure" unlikely to be realized through even the most efficacious monotherapy. Building on the success seen in the treatment of hepatitis C (HCV) and human immunodeficiency virus (HIV), combination therapy may be an essential strategy to improve efficacy and decrease viral breakthrough. Combinations acting on immune and viral targets are particularly attractive. However, creating synergy while balancing efficacy and safety remains a clear challenge. Various approaches to combination therapy are reviewed, highlighting strengths and challenges of each potential strategy. Overall, combination therapies are attractive as the next step towards cure and are a key strategy for achieving treatment with finite durations and durable endpoints.
尽管有安全有效的抗病毒药物和高效的保护性疫苗，慢性乙型肝炎仍然是一个严重的公共卫生问题。然而，目前的治疗很少能实现治愈，通常需要终身治疗，这导致了治疗接受率低和持续的发病率。对乙型肝炎病毒生命周期和宿主免疫反应的新认识扩大了药物治疗的潜在靶点，有一些有趣的抗病毒候选药物和处于早期开发阶段的新型免疫治疗方法。然而，乙肝病毒的持续存在是多因素的，这是由于肝内病毒库和持续的乙肝病毒介导的免疫失调，即使是最有效的单一疗法也不太可能实现“治愈”。基于丙型肝炎（HCV）和人类免疫缺陷病毒（HIV）治疗取得的成功，联合治疗可能是提高疗效和减少病毒突破的重要策略。作用于免疫和病毒靶点的联合治疗尤其具有吸引力。然而，在平衡疗效和安全性的同时产生协同作用仍然是一个明显的挑战。本文综述了联合治疗的各种方法，突出了每种潜在策略的优势和挑战。总体而言，联合治疗作为迈向治愈的下一步具有吸引力，并且是实现有限疗程和持久终点治疗的关键策略。
