Center for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department for Clinical Research, University of Southern Denmark, Odense, Denmark.
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
J Hepatol. 2024 Aug;81(2):345-359. doi: 10.1016/j.jhep.2024.03.035. Epub 2024 Mar 28.
The rising prevalence of liver diseases related to obesity and excessive use of alcohol is fuelling an increasing demand for accurate biomarkers aimed at community screening, diagnosis of steatohepatitis and significant fibrosis, monitoring, prognostication and prediction of treatment efficacy. Breakthroughs in omics methodologies and the power of bioinformatics have created an excellent opportunity to apply technological advances to clinical needs, for instance in the development of precision biomarkers for personalised medicine. Via omics technologies, biological processes from the genes to circulating protein, as well as the microbiome - including bacteria, viruses and fungi, can be investigated on an axis. However, there are important barriers to omics-based biomarker discovery and validation, including the use of semi-quantitative measurements from untargeted platforms, which may exhibit high analytical, inter- and intra-individual variance. Standardising methods and the need to validate them across diverse populations presents a challenge, partly due to disease complexity and the dynamic nature of biomarker expression at different disease stages. Lack of validity causes lost opportunities when studies fail to provide the knowledge needed for regulatory approvals, all of which contributes to a delayed translation of these discoveries into clinical practice. While no omics-based biomarkers have matured to clinical implementation, the extent of data generated has enabled the hypothesis-free discovery of a plethora of candidate biomarkers that warrant further validation. To explore the many opportunities of omics technologies, hepatologists need detailed knowledge of commonalities and differences between the various omics layers, and both the barriers to and advantages of these approaches.
与肥胖和过度饮酒相关的肝病患病率不断上升，这促使人们对准确的生物标志物的需求不断增加，这些标志物旨在用于社区筛查、脂肪性肝炎和显著纤维化的诊断、监测、预后以及治疗效果的预测。组学方法的突破和生物信息学的强大功能为将技术进步应用于临床需求创造了绝佳机会，例如开发用于个体化医疗的精准生物标志物。通过组学技术，可以在一个轴线上研究从基因到循环蛋白的生物学过程，以及微生物组，包括细菌、病毒和真菌。然而，基于组学的生物标志物发现和验证存在重要障碍，包括使用非靶向平台进行半定量测量，这可能表现出高分析、个体间和个体内差异。标准化方法并需要在不同人群中验证它们是一个挑战，部分原因是疾病的复杂性和不同疾病阶段生物标志物表达的动态性质。由于研究未能提供监管批准所需的知识而导致缺乏有效性，这一切都导致这些发现难以转化为临床实践。虽然还没有基于组学的生物标志物成熟到可以临床实施的程度，但生成的数据量之多足以支持对大量候选生物标志物进行无假设的发现，这些生物标志物需要进一步验证。为了探索组学技术的诸多机会，肝病学家需要详细了解各种组学层面之间的共同点和差异，以及这些方法的障碍和优势。
