The main objective of QUID-NASH is to develop a virtual liver biopsy for the diagnosis and grading of advanced NASH and its elemental lesions in T2D patients.Virtual here means that the information obtained is equivalent to that obtained with the histopathological examination of liver tissue, although elementary pieces of information are obtained through minimally invasive means (magnetic resonance, ultrasound, blood analyses) and processed using bioinformatics and biostatistics.
The clinical study implemented for that purpose consists in a prospective cross-sectional analysis of patients with T2D and liver abnormalities requiring a liver biopsy as part of standard care. Consenting patient undergo clinical and laboratory phenotyping, magnetic resonance imaging and ultrafast ultrasound examination for the collection of quantitative data; and collection of biologic fluids and liver tissue for genomic and metabolomics analyses. Gold standard for diagnosis is represented by a double histopathological reading of liver biopsy by independent pathologists. Algorithms constituting the virtual liver biopsy are elaborated on a training sample of 300 patients and validated in an independent sample of 300 patients.
The subsequent objective of QUID-NASH is to improve and deepen our knowledge of the pathophysiology of NASH through
The development and characterization of animal models of NASH, with a particular focus on developing a similar virtual liver biopsy that allows for longitudinal studies of natural and treated course of the disease and to critically evaluating the relevance of these models to human disease.
The identification of metabolic pathways implicated in the pathophysiology of NASH, and of targets relevant for therapeuticsby means of deep characterization through metabolomics, genomics, transcriptomics, and profiling of circulating microvesicles and immunophenotyping of cells in blood and liver, in liver tissue and blood from patients and experimental animals.
Eventually, the project will deliver:
Validated algorithms ready to enter the cycle of evaluation for the purpose of an introduction on the market as diagnostic biomarkers
A high quality data set on a group of a deeply phenotyped T2D patients with various lesions related to metabolic derangements, to be further exploited: cross-sectionally for any other purposes, and longitudinally for assessing the natural course and the impact of therapy by non-invasive but comprehensive means
Deeply characterized animal models for NASH with accurate non-invasive means for evaluation by non-invasive means of the natural and drug modified course
A data set on altered metabolic pathways and potential drug targets available for further characterization.