Chronic hepatitis B virus (HBV) infection remains a significant global health burden, affecting over 250 million people worldwide who are at risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). Currently available nucleos(t)ide analogues (NAs) are effective in controlling viraemia; however, functional cure, defined as loss of hepatitis B surface antigen (HBsAg), is rare and difficult to achieve and likely requires robust immune responses, reflecting the need for innovative therapeutic strategies.1 Thus, the future of treating chronic HBV infections relies on combination therapies that include both direct-acting antiviral agents and immunomodulatory agents.2 In this context, selgantolimod (SLGN), an agonist of Toll-like receptor 8 (TLR8), could be a promising candidate. Its efficacy in the treatment of chronic HBV infections has been investigated in preclinical models and clinical trials,3–5 but there remains limited understanding of its impact on immune effectors within the liver. The study by Roca Suarez and colleagues published in Gut 6 aimed to bridge that knowledge gap by characterising the transcriptomic changes and intercellular communication events induced by SLGN in the hepatic microenvironment and investigating its effect on HBV–host interactions. The researchers of Fabien Zoulim’s laboratory identified TLR8-expressing cell types in the …

中文翻译：

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免疫调节和进入抑制：selgantolimod 对乙型肝炎病毒的双重打击


慢性乙型肝炎病毒 （HBV） 感染仍然是一个重大的全球健康负担，影响着全球超过 2.5 亿有患肝硬化和肝细胞癌 （HCC） 风险的人。目前可用的核苷（酸）类似物 （NAs） 可有效控制病毒血症;然而，功能性治愈（定义为乙型肝炎表面抗原 （HBsAg） 的缺失）很少见且难以实现，并且可能需要强大的免疫反应，这反映了对创新治疗策略的需求.1 因此，治疗慢性 HBV 感染的未来依赖于包括直接抗病毒剂和免疫调节剂的联合疗法.2 在这种情况下，selgantolimod （SLGN）， Toll 样受体 8 （TLR8） 的激动剂可能是一个有前途的候选药物。其治疗慢性 HBV 感染的疗效已在临床前模型和临床试验中进行了研究，3-5 但对其对肝脏内免疫效应器的影响仍然了解有限。Roca Suarez 及其同事发表在 Gut 6 上的研究旨在通过表征 SLGN 在肝脏微环境中诱导的转录组变化和细胞间通讯事件并研究其对 HBV-宿主相互作用的影响来弥合这一知识差距。Fabien Zoulim 实验室的研究人员在...