@article{Song2026, 
author = {Rui Song and Shasha Yu and Xueyan Chen and Ning Ling and Dachuan Cai and Hong Ren and Min Chen},
title = {Activation of the Jak2/Stat3 pathway by ROS-dependent signaling cascades initiates hepatitis B virus-induced hepatic inflammatory responses},
year = {2026},
journal = {Genes & Diseases},
volume = {13},
number = {5},
keywords = {HBV, Liver inflammation, Mitochondrial respiration, ROS, Stat3},
url = {https://www.sciopen.com/article/10.1016/j.gendis.2025.101857},
doi = {10.1016/j.gendis.2025.101857},
abstract = {Chronic liver necroinflammation induced by hepatitis B virus (HBV) infection plays a major causative role in the development of end-stage liver diseases; however, mechanisms contributing to its initiation remain unclear. Analysis of the hepatic transcriptome from HBV-replication mice or HBV-infected patients revealed that significantly down-regulated mitochondrial oxidative phosphorylation function was the salient transcriptional feature at the early stage of liver inflammation compared with the stage without liver inflammation. In cell models, persistent HBV replication-induced progressive impairment of mitochondrial respiration resulted in increased reactive oxygen species (ROS) levels. We further discovered that HBV replication-induced ROS accumulation was essential for the up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2)-associated interleukin (IL)-6/IL-8 production, mediating the activation of Janus kinase 2 (Jak2)/signal transducer and activator of transcription (Stat3) signaling, and then the expression of downstream inflammatory genes. These observations were also identified in HBV-replication mice at the early stage of liver inflammation, which exhibited elevated hepatic oxidative stress, Nrf2 expression, IL-6 and IL-8 production, and Jak2/Stat3 activation, alongside hepatic inflammatory cell infiltration. In vivo, ROS scavenging with N-acetylcysteine (NAC) mitigated these effects. Our findings underscore the critical role of ROS-dependent Jak2/Stat3 pathway activation in the occurrence of HBV-induced liver inflammation, providing new insights into the pathogenesis of chronic hepatitis B.}
}