Table 5_Investigation of the relationship between chronic hepatitis B and tuberculosis using bioinformatics and systems biology approaches.xlsx

BackgroundHepatitis B virus (HBV) is a globally prevalent pathogen that poses significant public health challenges. Active HBV replication can trigger immune responses that result in liver damage. Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the leading causes of death from a single infectious agent worldwide. Notably, in TB patients with HBV infection and, the incidence of adverse events is six times higher than in those with TB alone, and HBV infection increases the risk of latent TB. However, the relationship between HBV and TB have not been thoroughly investigated.
MethodsTo elucidate the relationship between HBV and TB, we performed an integrated bioinformatics analysis using expression profiling and RNA sequencing data from the GSE83148 and GSE126614 datasets. We identified differentially expressed genes (DEGs) associated with both diseases and analyzed shared biological pathways, key genes, transcriptional regulatory networks, and gene-disease associations. Furthermore, we predicted potential therapeutic agents targeting these shared molecular features.
ResultsA total of 35 overlapping DEGs were identified for in-depth analysis. Functional enrichment revealed that these genes are involved in both immune-related pathways and cellular metabolic regulation, underscoring their potential role in the progression of HBV and TB. Protein–protein interaction (PPI) network analysis highlighted four hub genes: CCL2, CD69, EGR2, and CCL20. Additionally, 35 transcription factors (TFs) were predicted to regulate these hub genes. Several candidate drugs, including etoposide, 8-azaguanine, menaquinone, emetine and N-acetyl-L-cysteine, were identified as potential therapeutic options. The DEGs were also significantly associated with other conditions such as pneumonia.
ConclusionThis study provides novel insights into the relationship between HBV and TB, offering potential targets for diagnosis and treatment. Our findings may contribute to the development of integrated strategies to manage HBV infection and TB more effectively.

背景
乙型肝炎病毒（HBV）是全球范围内广泛流行的病原体，对公共卫生构成严峻挑战。HBV活动性复制可触发免疫反应，进而导致肝脏损伤。由结核分枝杆菌（Mycobacterium tuberculosis, Mtb）引起的结核病（TB），仍是全球单一传染源导致死亡的主要病因之一。值得注意的是，合并HBV感染的结核病患者，其不良事件发生率是单纯结核病患者的6倍；且HBV感染会增加潜伏性结核的发病风险。然而，HBV与TB之间的关联尚未得到充分研究。
方法
为阐明HBV与TB之间的关联，本研究整合分析了GSE83148与GSE126614数据集的表达谱及RNA测序数据。我们筛选出与两种疾病相关的差异表达基因（differentially expressed genes, DEGs），并分析了二者共享的生物学通路、关键基因、转录调控网络以及基因-疾病关联。此外，我们还针对这些共享分子特征，预测了潜在的治疗药物。
结果
本研究共筛选出35个重叠的差异表达基因，用于后续深入分析。功能富集分析结果显示，这些基因参与免疫相关通路与细胞代谢调控，提示其在HBV与TB的疾病进展中可能发挥重要作用。蛋白质-蛋白质相互作用（protein–protein interaction, PPI）网络分析筛选出4个核心枢纽基因：CCL2、CD69、EGR2及CCL20。此外，本研究预测得到35个可调控这些枢纽基因的转录因子（transcription factors, TFs）。本研究还确定了依托泊苷、8-氮鸟嘌呤、甲萘醌、吐根碱及N-乙酰-L-半胱氨酸等多种候选治疗药物。这些差异表达基因还与肺炎等其他疾病状态显著相关。
结论
本研究为HBV与TB之间的关联提供了新的见解，为二者的诊断与治疗提供了潜在靶点。本研究结果有助于开发整合性干预策略，以更有效地开展HBV感染与结核病的临床管理。