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Serum Markers of Liver Fibrosis: Combining the BIPED Classification and the Neo-Epitope Approach in the Development of New Biomarkers

机译:肝纤维化血清标志物:结合BIPED分类和新表位方法开发新的生物标志物

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摘要

Background: Fibrosis is a central histological feature of chronic liver diseases and is characterized by the accumulation and reorganization of the extracellular matrix. The gold standard for assessment of fibrosis is histological evaluation of a percutaneous liver biopsy. Albeit a considerable effort have been invested in finding alternative non-invasive approaches, these have not been sufficiently succesfull to replace biopsy assessment. Aim: To identify the extracellular matrix proteins of interest, that as protein degradation fragments produced during extracellular matrix metabolism neo-epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (>Burden of disease, >Investigative, >Prognostic, >Efficacy and >Diagnostic) to characterise present serological markers. Methods: Pubmed was search for keywords; Liver fibrosis, neo-epitopes, biomarkers, clinical trail, extra cellular matrix, protease, degradation, fragment. Results and Conclusion: Implementation of BIPED categorization in the development and validation of fibrosis biomarkers to simplify and standardize the use of existing and future biomarkers seems advantageous. In addition, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis.
机译:背景:纤维化是慢性肝病的主要组织学特征,其特征是细胞外基质的积累和重组。评估纤维化的金标准是经皮肝活检的组织学评估。尽管在寻找替代性非侵入性方法上进行了大量的努力,但这些方法还不足以取代活检评估。目的:鉴定感兴趣的细胞外基质蛋白,将其作为细胞外基质代谢过程中产生的新表位的蛋白质降解片段,可作为纤维化中新型生化标记物开发的目标。我们使用了最近提出的BIPED系统(> B 疾病,> I 研究性,> P 侏儒性,> E 有效性和> D 具有诊断性)来表征当前的血清学标记物。方法:Pubmed搜索关键词;肝纤维化,新表位,生物标志物,临床试验,细胞外基质,蛋白酶,降解,片段。结果与结论:在纤维化生物标志物的开发和验证中实施BIPED分类,以简化和标准化现有和未来生物标志物的使用似乎是有利的。另外,新表位方法的系统使用,即在细胞外重塑过程中由蛋白质的酶促切割产生的肽表位的定量,可能在寻找肝脏纤维化的新标志物方面具有生产价值。

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