The Role of Diagnostic Biomarkers, Omics Strategies, and Single-Cell Sequencing for Nonalcoholic Fatty Liver Disease in Severely Obese Patients.

The Role of Diagnostic Biomarkers, Omics Strategies, and Single-Cell Sequencing for Nonalcoholic Fatty Liver Disease in Severely Obese Patients.
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诊断生物标志物、组学策略及单细胞测序在重度肥胖患者非酒精性脂肪性肝病中的作用

DOI:
10.3390/jcm10050930
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发表时间:
2021-03-01
影响因子:
3.9
通讯作者:
Thiele M
Thiele M
中科院分区:
医学2区
文献类型:
--
作者:
Wernberg CW;Ravnskjaer K;Lauridsen MM;Thiele M

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代谢功能障碍所致的肝脏疾病已成为一个在全球范围内日益严峻的健康问题。重度肥胖是非酒精性脂肪性肝病(NAFLD)尤为突出的危险因素,高达93% 的重度肥胖患者受其影响。目前的诊断标志物主要聚焦于检测晚期肝纤维化,这是肝脏相关发病和死亡的主要预测指标。最准确的诊断工具是利用弹性成像技术测量肝脏硬度,其诊断准确性在体重正常和重度肥胖患者中相近。然而,对于腹围和皮下脂肪极厚的患者,弹性成像工具的有效性会因设备及测量质量的限制而受到影响。因此,基于血液的生物标志物颇具吸引力,但目前可用的此类标志物诊断准确性仅为中等。基因组学、转录组学和蛋白质组学等组学技术的不断进步,为发现生物标志物以及增进对非酒精性肝病和脂肪性肝炎病理生理的理解带来了巨大希望。最新进展已实现单细胞测序以及对基因表达和功能的细胞类型解析。因此,在不久的将来,随着对健康肝脏和受损肝脏中各细胞类型生物学功能理解的加深,我们很可能会看到大量突破性的生物标志物问世。
Liver disease due to metabolic dysfunction constitute a worldwide growing health issue. Severe obesity is a particularly strong risk factor for non-alcoholic fatty liver disease, which affects up to 93% of these patients. Current diagnostic markers focus on the detection of advanced fibrosis as the major predictor of liver-related morbidity and mortality. The most accurate diagnostic tools use elastography to measure liver stiffness, with diagnostic accuracies similar in normal-weight and severely obese patients. The effectiveness of elastography tools are however hampered by limitations to equipment and measurement quality in patients with very large abdominal circumference and subcutaneous fat. Blood-based biomarkers are therefore attractive, but those available to date have only moderate diagnostic accuracy. Ongoing technological advances in omics technologies such as genomics, transcriptomics, and proteomics hold great promise for discovery of biomarkers and increased pathophysiological understanding of non-alcoholic liver disease and steatohepatitis. Very recent developments have allowed for single-cell sequencing and cell-type resolution of gene expression and function. In the near future, we will therefore likely see a multitude of breakthrough biomarkers, developed from a deepened understanding of the biological function of individual cell types in the healthy and injured liver.
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