In this case Study (Fat Diet NASH Mouse model N=4, vs Drug A and Drug B candidates, N=4) we highlight the combined efficacy of the drug candidates as anti-steatotic and and-fibrotic compounds. Dots are the group averages. Our method uses ONE FFPE slide to derive all the information. Turnaround time is les than 2 weeks for a typical 4 arms x 4 animals study.

Fibrosis Phenotyping establishes pre-clinical continuous scores to assess the severity and progression of fibrosis.

Phenotype Maps.JPG

Fibrosis Phenotyping establishes clinical continuous scores to assess the severity and progression of fibrosis.

Fig. 1 and 2: Retrospective NASh Adult Cohort with N=98, F0(24), F1(24), F2(25), F3(20) and F4(5).  Accepted for presentation at AASLD 2019:  Title: Evaluation of a novel two‐photon microscopy‐based fibrosis phenotypic composite score and its correlation with serum neo-epitope collagen biomarkers in patients with NASH Authors: Li Chen1, Yi Luo, Faridoddin Mirshahi, Anthony Azzara, Arun Sanyal, Mathieu Petitjean  Fig 3: Retrospective NASH Pediatric Cohort with F0(29), F1(43), F2(10), F3(7), F4(0)  Accepted for presentation at AASLD 2019)   Title:  Development of an Optimal Continuous Pediatric Fibrosis Score to Assess Severity and Progression of Fibrosis in Non-alcoholic Fatty Liver Disease (NAFLD).  Authors : Elena Reynoso, Li Chen, Mathieu Petitjean, Cynthia Behling, Joel Lavine

Fig. 1 and 2: Retrospective NASh Adult Cohort with N=98, F0(24), F1(24), F2(25), F3(20) and F4(5). Accepted for presentation at AASLD 2019: Title: Evaluation of a novel two‐photon microscopy‐based fibrosis phenotypic composite score and its correlation with serum neo-epitope collagen biomarkers in patients with NASH Authors: Li Chen1, Yi Luo, Faridoddin Mirshahi, Anthony Azzara, Arun Sanyal, Mathieu Petitjean

Fig 3: Retrospective NASH Pediatric Cohort with F0(29), F1(43), F2(10), F3(7), F4(0) Accepted for presentation at AASLD 2019) Title: Development of an Optimal Continuous Pediatric Fibrosis Score to Assess Severity and Progression of Fibrosis in Non-alcoholic Fatty Liver Disease (NAFLD). Authors: Elena Reynoso, Li Chen, Mathieu Petitjean, Cynthia Behling, Joel Lavine

Continuous Scores can show the real effect of a compound

As opposed to Categorical Scores, Fibrosis Continuous scores can reveal the real benefit of a therapeutic Compound (as illustrated below, in Red: A patient moving from F1+ to F1- is not identified to from the treatment using categorical scores (left figure), while continuous score show it (right figure).

Long-term obeticholic acid treatment is associated with improvements in collagen morphometry in patients with primary biliary cholangitis.  Andreas E. Kremer, Christopher L. Bowlus, Pierre Bedossa, Albert Parés, Lisa M. Forman, Joost P.H. Drenth, Stephen Ryder, Luigi Terracciano, Yuying Jin, Alexander Liberman, Richard Pencek, Leigh MacConell, Paul J. Pockros

Long-term obeticholic acid treatment is associated with improvements in collagen morphometry in patients with primary biliary cholangitis. Andreas E. Kremer, Christopher L. Bowlus, Pierre Bedossa, Albert Parés, Lisa M. Forman, Joost P.H. Drenth, Stephen Ryder, Luigi Terracciano, Yuying Jin, Alexander Liberman, Richard Pencek, Leigh MacConell, Paul J. Pockros

Early result support the hypothesis that there are multiple forms of fibrosis and that the related fibrosis phenotypes are very heterogeneous. The case study (below) shows that FibroNest can help classify pediatric patients with NASH-1 and NASH-2 forms, two well described forms of NASH. Further validation studies are on-going. We welcome investigator initiated study proposals in this field.

Is Fibrosis Phenotyping a novel tool for patient classification ?

Pediatric NASH Phenotyping.JPG

Second Harmonic Generation Reveals Subtle Fibrosis Differences in Adult and Pediatric Nonalcoholic Fatty Liver Disease. Liu F, Zhao JM, Rao HY, Yu WM, Zhang W, Theise ND, Wee A, Wei L.  Am J Clin Pathol. 2017 Nov 20;148(6):502-512

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Modeling the epidemic of Nonalcoholic Fatty Liver Disease demonstrates an exponential increase in burden of disease C. Estes, H. Razavi, R. Loomba, Z. Younossi, A.sanyal, Hepatology (67) 1, 2018

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The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from th American Association for the Study of Liver Diseases. N. Chalasani, Z. Younossi, J.E. Lavine, M. Charlton, K. Cusi, M. Rinella, S. Harrison, E. Brunt, A.J. Sanyal  in Hepatology ,Vol. 67, No.1. Jan 2018

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Current concepts in pediatric nonalcoholic fatty liver disease S. Fleet, J. Lefkowitch,  J. Lavine Gastroenterol Clin N Am 46 (2017) 217–231

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Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score and the Histopathologic Diagnosis in NAFLD: Distinct Clinicopathologic Meanings, Elizabeth M. Brunt, David E. Kleiner, Laura A. Wilson, Patricia Belt, and Brent A. Neuschwander-Tetri for the NASH Clinical Research Network (CRN)

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Liver biopsy in modern clinical practice: a pediatric point-of-view N. Ovchinsky, R. K.Moreira, J.H. Lefkowitch, J.E. Lavine Adv Anat Pathol. 2012 Jul;19(4):250-62

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The intersection of nonalcoholic fatty Liver disease and obesity. J.A. Woo Baidal and J.E. Lavine Science Translational Medicine  27 January 2016 Vol 8 Issue 323

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Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Ratziu et all. Gastroenterology 2005 Jun; 126(7): 1898-906 

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