Vyas A K, Jindal A, Hissar S, Ramakrishna G, Trehanpati N
Department of Molecular and Cellular Medicine, Institute of Liver & Biliary Sciences, New Delhi, India.
Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India.
Scand J Immunol. 2017 Jul;86(1):4-14. doi: 10.1111/sji.12553.
Chronic hepatitis B virus (HBV) infection affects millions of people worldwide and about half a million people die every year. India represents the second largest pool of chronic HBV infections with an estimated 40 million chronically infected patients. Persistence or clearance of HBV infection mainly depends upon host immune responses. Chronically infected individuals remain in immune tolerant phase unless HBV flares and leads to the development of chronic active hepatitis or acute-on-chronic liver failure. Strategies based on inhibition of viral replication (nucleoside analogues) or immune modulation (interferons) as monotherapy, or in combination in sequential therapies, are currently being used globally for reducing HBV viral load and mediating HBsAg clearance. However, the immune status and current therapies for promoting sustained virological responses in HBV-infected patients remain suboptimal. Elimination of cccDNA is major challenge for future therapies, and new molecules such as NTCP, Toll-like receptor (TLR)7 agonist (GS9620) and cyclophilin have emerged as potential targets for preventing HBV entry and replication. Other than these, HBV cccDNA elimination is the major target for future therapies.
慢性乙型肝炎病毒（HBV）感染影响着全球数百万人，每年约有50万人死亡。印度是慢性HBV感染人数第二多的国家，估计有4000万慢性感染患者。HBV感染的持续或清除主要取决于宿主免疫反应。慢性感染个体处于免疫耐受期，除非HBV发作并导致慢性活动性肝炎或慢加急性肝衰竭。目前全球正在使用基于抑制病毒复制（核苷类似物）或免疫调节（干扰素）的单一疗法，或在序贯疗法中联合使用，以降低HBV病毒载量并介导HBsAg清除。然而，HBV感染患者的免疫状态和促进持续病毒学应答的当前疗法仍不理想。消除cccDNA是未来治疗的主要挑战，诸如钠-牛磺胆酸共转运多肽（NTCP）、Toll样受体（TLR）7激动剂（GS9620）和亲环素等新分子已成为预防HBV进入和复制的潜在靶点。除此之外，消除HBV cccDNA是未来治疗的主要目标。
