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

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。

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.