免疫检查点抑制剂在慢性乙型肝炎中的研究进展

Immune checkpoint inhibitors in chronic hepatitis B

摘要:

慢性乙型肝炎病毒（hepatitis B virus，HBV）感染仍是全球主要公共卫生问题之一。尽管目前已有预防性疫苗可有效预防新发HBV感染，但全球仍有约2.5亿慢性HBV感染者，其中每年约有100多万人死于HBV相关的慢性肝病，形势仍不容乐观。抗病毒药物（干扰素和核苷类似物等）可抑制病毒复制，降低乙肝相关并发症，但由于其存在耐药性难以达到临床终点。免疫检查点抑制剂作为逆转T细胞耗竭的重要策略，重建有效的功能T细胞反应将是治疗慢性乙肝患者一种有前景的免疫调节方法。本文总结了程序性死亡受体1/细胞程序性死亡-配体1（PD-1/PD-L1）、细胞毒性T淋巴细胞相关蛋白4（CTLA-4）、T细胞免疫球蛋白和ITIM结构域（TIGIT）、T细胞免疫球蛋白和粘蛋白域蛋白-3（Tim-3）、淋巴细胞活化基因-3（lag-3）五种免疫检查点分子的抑制剂在慢性乙型肝炎中的重要研究进展。

Abstract:

Chronic hepatitis B virus (HBV) infection remains a significant worldwide medical problem. Despite the availability of an effective prophylactic vaccine, an estimated 250 million individuals worldwide are chronically infected. Chronic infection leads to over 1 million deaths annually. Currently, interferon-alpha (IFN-α) and nucleoside/nucleotide analogues drugs are available and reduce both new infection rates and the development of liver disease in HBV-positive persons, but it is difficult to achieve the ideal clinical treatment endpoint. Immune checkpoint inhibitors are an important strategy for reversing T cell exhaustion, that aims at reinvigorating dysfunctional T cells represents a promising approach to induce a functional cure of a chronic infection. In this review, we summarize the recent advances in immune checkpoint inhibitors of programmed death receptor 1/cell programmed death ligand 1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T-cell immunoglobulin and ITIM domin (TIGIT), T-cell immunoglobulin and mucin domin protein-3 (Tim-3), and lymphocyte activation gene-3 (Lag-3) in chronic hepatitis B.