Current progress in the pathophysiology and potential therapeutic targets of acute-on-chronic liver failure through multiomics approaches

Abstract Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome that develops in patients with chronic hepatitis or liver cirrhosis. It is characterized by a high mortality rate, rapid progression, and complex pathological mechanisms. As it often involves multiorgan failure (e.g., of the liver, kidneys, and brain), traditional clinical indicators have limited predictive value and cannot support accurate, personalized treatment. However, the rapid development of omics sequencing technologies in recent years (e.g., genomics, transcriptomics, proteomics, metabolomics, and microbiomics) has provided unprecedented opportunities to analyze the molecular mechanisms of ACLF, discover novel biomarkers, and develop precise intervention strategies. Multiomics technology is an approach that systematically studies complex biological mechanisms of ACLF by integrating data from multiple omics disciplines. This approach overcomes the limitations of single-omics techniques, and offering a more comprehensive view of disease mechanisms, biomarker discovery, and precision medicine. In this review, we summarize studies on whole-genome sequencing, single-cell ribonucleic acid (RNA) sequencing, proteomics, lipidomics, and metabolomics in patients with ACLF and discuss associations between expression patterns, disease progression and prognosis, and the interconnections among multiomics.