代谢组学与病证结合的自身免疫性肝炎诊断模式构建

Autoimmune hepatitis (AIH) is a serious disease, and the incidence of which is dramatically increasing. It is a key factor to make a quick and accurate diagnosis and treatment to prevent the progression of AIH. However, due to unknown pathogenesis, atypical clinical manifestations and overlap syndrome, the current diagnostic methods for AIH still have many problems, such as complex and time consuming diagnostic procedures, limited sensitivity and specificity. Therefore, there is an obvious clinical need for new methods that help to diagnose AIH in clinical study of liver diseases. In the early stage, the AIH diagnostic markers were screened by the combination of disease and metabolic syndrome, and found that the TCM syndromes related metabolic markers could be residual, limiting the application of scientific research achi-evements to clinical transformation. Therefore, based on the previous research, this project innovatively propose using metabonomics research method combined with disease and syndrome to screen specific diagnostic markers for AIH. The metabolic markers of TCM syndromes would exclude from the metabolic markers of disease of AIH. Combined with the immune, biochemical and pathological detection indicators, comprehensive analysis of the clinical significance of AIH diagnostic markers, which would provide reference for the establish-ment of an objective scientific AIH diagnostic index system.

自身免疫性肝炎（AIH）是一种严重的进行性疾病，发病率逐年升高。对其作出快速准确的诊断和治疗是阻止病情恶化的关键因素，但由于病因复杂，临床表现不典型、伴发重叠综合征等因素，目前AIH的诊断存在过程繁杂、周期长、敏感性和特异性低等问题。探索建立新的AIH诊断方法一直是科研与临床研究的重点和难点，具有重要的临床应用价值。课题组前期运用“病-代谢组学”组合模式筛查AIH诊断标志物，发现此模式会导致“证”相关生物标志物的残留，限制了科研成果向临床的转化应用。因此，本项目结合前期研究基础，创新性地提出采用代谢组学与病-证结合的方法筛查AIH特异性诊断标志物。在采用“病-代谢组学”模式筛查AIH“病”生物标志物的基础上，排除不同证型的“证”标志物影响，以期获得更特异、更敏感的AIH诊断标志物；结合免疫、生化和病理学检测指标，构建新的AIH诊断模式，为临床获取更为便捷、有效的AIH诊断指标体系提供参考。

自身免疫性肝炎（AIH）是一种严重的进行性疾病，发病率逐年升高。对其作出快速准确的诊断和治疗是阻止病情恶化的关键因素，但由于病因复杂，临床表现不典型、伴发重叠综合征等因素，目前AIH的诊断存在过程繁杂、周期长、敏感性和特异性低等问题。探索建立新的AIH诊断方法一直是科研与临床研究的重点和难点，具有重要的临床应用价值。项目组认真执行和组织实施项目中的计划和指标。首先，建立了自身免疫性肝病（autoimmune liver diseases, AILD）医学数据库，并建立样品与病历、样品与生化指标之间的信息关联；其次，应用核磁共振方法测定健康人群及AILD各证型患者血浆、尿液的1H NMR谱，分别获得各型AILD患者的代谢组学测试指纹图谱和数据；第三，采用PLS-DA数学建模方法分析比较AIH与PBC、OS、健康人群之间的代谢谱差异，建立AIH“病”和“证”相关生物标志物体系，初步确定AIH诊断相关生物标志物。第四，进行了基于小样本的AIH诊断相关生物标志物的前瞻性验证研究；第五，开展AIH诊断相关生物标志物在预测疾病转归中的作用研究。该研究对自身免疫性肝炎的诊断研究具有一定的参考价值。