Non-invasive quantification of liver health in NASH (N-QUAN): A prospective diagnostic accuracy study

摘要 非酒精性脂肪性肝炎（NASH）可导致严重结局，包括失代偿性 肝硬化（即晚期肝病），心脏病和肝癌的风险增加， 没有可用的治疗。肝活检是目前唯一批准的试验纳入测试， NASH临床试验中的终点评估是侵入性的，昂贵的，不可靠的，对 疾病的异质性和不可接受的许多患者。 在这个项目中，Perspectum试图完成必要的证据，以证明MRI衍生 生物标志物铁校正T1（cT1）作为诊断富集生物标志物，与 临床风险因素，以确定更有可能出现肝脏组织病理学结果的患者 适合纳入NASH临床试验。cT1已显示出作为富集生物标志物的前景 通过区分NAS≥4和F≥2的NASH患者， 组织病理学，从那些没有。 利用U01合作协议提案的资金， 与FDA合作，我们将完成活检配对单门，前瞻性，交叉， 在225名患者中进行的部分观察性研究。 本研究的cT1目标有两个方面，并且相互依赖： ·在疑似NASH患者中进行肝活检，以评估诊断NASH的诊断性指标。 cT1在区分NAS≥4和F≥2的NASH患者与 没有. ·评估cT1与NASH组织病理学特征之间的相关性。 这项研究将在多个地点进行，包括西奈山的伊坎医学院， 德克萨斯州肝脏中心，弗吉尼亚大学，弗吉尼亚联邦大学，拉什大学 芝加哥和亚利桑那州肝脏健康谁将包括他们的病人的代表性样本 研究期间的人群。

Abstract Non-alcoholic steatohepatitis (NASH) can lead to severe outcomes including decompensated cirrhosis (i.e. advanced liver disease), increased risk of heart disease and liver cancer, and there are no treatments available. Liver biopsy is currently the only approved test for trial inclusion and endpoint assessment in NASH clinical trials, which is invasive, costly, unreliable, is insensitive to disease heterogeneity and unacceptable to many patients. In this project, Perspectum seeks to complete the necessary evidence to qualify the MRI derived biomarker iron-corrected T1 (cT1) as a diagnostic enrichment biomarker, used in conjunction with clinical risk factors, to identify patients who are more likely to have liver histopathologic findings appropriate for inclusion in NASH clinical trials. cT1 has shown promise as an enrichment biomarker and could reduce the use of liver biopsy, by discriminating NASH patients with NAS≥4 & F≥2 on histopathology, from those without. With the funding from this U01 Cooperative Agreement proposal and leveraging the close collaboration with the FDA, we will complete a biopsy-paired single-gate, prospective, cross- sectional, observational study in 225 patients. The objectives for cT1 in this study are two-fold and interdependent: · To evaluate, in patients with suspected NASH referred for Liver biopsy, the diagnostic performance of cT1 at discriminating those NASH patients with NAS≥4 & F≥2 from those without. · To assess the correlation between cT1 and histopathological features of NASH. The study will be carried out at multiple sites including Icahn School of Medicine at Mount Sinai, Liver Center of Texas, University of Virginia, Virginia Commonwealth University, Rush University Chicago, and Arizona Liver Health who will include a representative sample of their patient population over the study duration.