Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, the Netherlands.
Department of Medicine, Division of Gastroenterology and Division of Infectious Diseases, University of Minnesota, Minneapolis, Minnesota, USA.
J Infect Dis. 2022 Mar 15;225(6):1081-1090. doi: 10.1093/infdis/jiab381.
Inactive carrier phases in chronic hepatitis B virus (HBV) infection present minimal liver disease and HBV replication activity suggesting partial immune reconstitution, although the mechanisms responsible remain elusive. Moreover, hepatitis B surface antigen (HBsAg) production-hypothesized to modulate the immune response-is unaltered. In the current study, we assessed the intrahepatic transcriptome in inactive carriers of HBV versus healthy liver donors, including in the context of diverse HBsAg levels (serum and liver), to better understand the phenomenon of immune control. We found a deregulated liver transcriptome in inactive carriers compared with healthy controls, despite normal liver function. Moreover, diverse HBsAg levels have minimal impact on the liver transcriptome in inactive carriers, although gene correlation analysis revealed that leukocyte activation, recruitment, and innate responses genes were correlated with liver HBsAg levels. These findings provide more insight into the mechanisms underlying anti-HBV strategies currently under development, aimed at interfering with HBsAg production or inducing a state of immune control.
慢性乙型肝炎病毒（HBV）感染中的非活动型携带状态表现出轻微的肝脏疾病和 HBV 复制活性，提示部分免疫重建，尽管其负责的机制仍不清楚。此外，乙型肝炎表面抗原（HBsAg）的产生——据推测会调节免疫反应——并未改变。在本研究中，我们评估了 HBV 非活动型携带者与健康供体肝脏之间的肝内转录组，包括在不同 HBsAg 水平（血清和肝脏）的背景下，以更好地了解免疫控制现象。尽管肝功能正常，但与健康对照组相比，非活动型携带者的肝转录组存在失调。此外，非活动型携带者中不同的 HBsAg 水平对肝转录组的影响很小，尽管基因相关性分析显示白细胞激活、募集和固有反应基因与肝 HBsAg 水平相关。这些发现为目前正在开发的抗 HBV 策略的潜在机制提供了更深入的了解，这些策略旨在干扰 HBsAg 的产生或诱导免疫控制状态。
