PDF(Pubmed)
Abstract：
Acute-on-chronic liver failure (ACLF) is a major cause of liver-related death worldwide, but its key pathological features remain incompletely defined. This study aimed to reveal the molecular basis of hepatitis B virus-related ACLF (HBV-ACLF) by transcriptome sequencing of human liver tissue. A total of 18 human liver tissues from patients with different stages of HBV-related disease were collected for RNA sequencing, and liver tissues from patients and mouse models with ACLF were used for subsequent validation. Specifically, 6,853 differentially expressed genes (DEGs) and 5,038 differentially expressed transcripts were identified in patients with ACLF compared to patients with chronic hepatitis B (CHB) and normal controls (NCs). Investigation of functional by KEGG pathway enrichment analysis revealed prominent immune and metabolic dysregulation at the ACLF stage. We found that the key genes FGF19, ADCY8 and KRT17, which are related to immunometabolic disturbances, were significantly upregulated in the progression of ACLF. The three key genes were validated in human and mouse samples, indicating their prognostic and therapeutic potential in ACLF. In summary, our work reveals that immunometabolic disorder is involved in HBV-ACLF pathogenesis and indicates that FGF19, ADCY8 and KRT17 may be sensitive biomarkers for HBV-related ACLF.
摘要：
慢性急性肝衰竭（ACLF）是全球肝脏相关死亡的主要原因，但其关键病理特征仍未完全定义。本研究旨在通过人肝组织转录组测序揭示乙型肝炎病毒相关ACLF（HBV-ACLF）的分子基础。从HBV相关疾病的不同阶段的患者共收集18人肝组织进行RNA测序，和来自患有ACLF的患者和小鼠模型的肝组织用于随后的验证。具体来说,与慢性乙型肝炎（CHB）和正常对照（NC）患者相比，在ACLF患者中鉴定了6,853个差异表达基因（DEGs）和5,038个差异表达转录本。通过KEGG途径富集分析进行的功能研究揭示了ACLF阶段突出的免疫和代谢失调。我们发现与免疫代谢紊乱相关的关键基因FGF19、ADCY8和KRT17,在ACLF的进展中显著上调。在人类和小鼠样本中验证了这三个关键基因，表明其在ACLF中的预后和治疗潜力。总之,我们的工作揭示免疫代谢紊乱与HBV-ACLF发病机制有关,提示FGF19,ADCY8和KRT17可能是HBV相关ACLF的敏感生物标志物.
