January 2023 - Wang et Al

January 2024 - Watson et Al

PUBLICATIONS FROM OUR COLLABORATORS AND OUR TEAM:

Liver fibrosis phenotyping and severity scoring by quantitative image analysis of biopsy slides. Adam Watson, Louis Petitjean, Mathieu Petitjean, Michael Pavlides.

Liver International, November 27 2023, DOI: 10.1111/liv.15768

Digital pathology with artificial intelligence analysis provides insight to the efficacy of anti-fibrotic compounds in human 3D MASH model. Radina Kostadinova, Simon Ströbel, Li Chen, Katia Fiaschetti‑Egli, Jana Gadient, Agnieszka Pawlowska, Louis Petitjean, Manuela Bieri, Eva Thoma & Mathieu Petitjean

Nature, Scientific Reports, Sci Rep 14, 5885 (2024). doi.org/10.1038/s41598-024-55438-2

Thrombospondin 2, matrix Gla protein and digital analysis to stratify fibroblast populations in fibrostenosing Crohn`s disease". Miha Jerala, Tinkara Remic, Nina Hauptman, Pia Homan, Neža Zajšek, Mathieu Petitjean, Li Chen, Nina Zidar

In Print: Virchows Archiv: European Journal of Pathology

Digital pathology and artificial intelligence in non-alcoholic steatohepatitis: current status and future directions. Vlad Ratziu, Marcus Hompesch, Mathieu Petitjean, Cindy Serdjebi, Janani S. Iyer, Anil V. Parwani, Dean Tai, Elisabetta Bugianesi, Kenneth Cusi, Scott L. Friedman, Eric Lawitz, Manuel Romero-Gómez, Detlef Schuppan, Rohit Loomba, Valérie Paradis, Cynthia Behling, Arun J. Sanyal.

Journal of Hepatology, October 2023. doi.org/10.1016/j.jhep.2023.10.015

Breakthroughs in therapies for NASH and remaining challenges, Vlad Ratziu, Sven Francque, Arun Sanyal,

Journal of Hepatology 2022 vol. 76 j 1263–1278

Semaglutide Has Beneficial Effects on Non-Alcoholic Steatohepatitis in Ldlr-/-.Leiden Mice. José A. Inia 1,2,3, Geurt Stokman 1 , Martine C. Morrison 1 , Nicole Worms 1, Lars Verschuren 4 ,Martine P. M. Caspers 4 , Aswin L. Menke 1 , Louis Petitjean 5, Li Chen 5 , Mathieu Petitjean 5, J. Wouter Jukema 2,3,6, Hans M. G. Princen 1 and Anita M. van den Hoek 1 | 1 Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands | 2 Cardiology, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands | 3 Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands | 4 Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands | 5 PharmaNest Inc., Princeton, NJ 08540, USA | 6 Netherlands Heart Institute, 3511 EP Utrecht, The Netherlands.

International Journal of Molecular Sciences. 2023; 24 (10):8494. | doi.org/10.3390/ijms24108494

An autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in nonalcoholic steatohepatitis. Shuang Wang (Icahn Mount Sinai), Kenneth Li (Icahn Mount Sinai); Eliana Pickholz Li (Icahn Mount Sinai); Ross Dobie (University of Edinburgh, UK); Kylie P. Matchett (University of Edinburgh, UK); Neil C. Henderson (University of Edinburgh, UK); Chris Carrico (Gordian Biotechnology, CA); Ian Driver (Gordian Biotechnology, CA); Martin Borch Jensen (Gordian Biotechnology, CA); Li Chen PharmaNest, Inc., NJ); Mathieu Petitjean (PharmaNest, Inc.,NJ); Dipankar Bhattacharya (Icahn Mount Sinai); Maria I. Fiel (Icahn Mount Sinai); Xiao Liu (University of California); Tatiana Kisseleva (University of California); Uri Alon (Weizmann Institute of Science, Israel); Miri Adler (Yale University School of Medicine, CT); Ruslan Medzhitov (Yale University School of Medicine, CT), Scott Friedman (Icahn Mount Sinai).

Science Translational Medicine, 4 Jan 2023, Vol 15, issue 677 | DOI: 10.1126/scitranslmed.add3949

Automated fibrosis phenotyping of liver tissue from non-tumor lesions of patients with and without hepatocellular carcinoma after liver transplantation for non-alcoholic fatty liver disease. Nakamura Y, Miyaaki H, Miuma S, et al. Hepatol Int. 2022;16(3):555-561. doi:10.1007/s12072-022-10340-9 (weblink)

Long-term obeticholic acid treatment is associated with improvements in collagen morphometry in patients with primary biliary cholangitis. Andreas E. Kremer 1, Christopher L. Bowlus, Pierre Bedossa, Albert Parés, Lisa M. Forman, Joost P.H. Drenth, Stephen Ryder, Luigi Terracciano, Yuying Jin, Alexander Liberman 1, Richard Pencek 1, Leigh MacConell 1, Paul J. Pockros - 1 Intercept Pharmaceuticals, San Diego, USA

Clinical Journal of Gastroenterology and Hepatolohy | doi.org/10.1016/j.cgh.2019.09.050 - here

INT-767 improves histopathological features in a diet-induced ob/ob mouse model of biopsy-confirmed non-alcoholic steatohepatitis (NASH). Jonathan D Roth 1, Michael Feigh 1 , Sanne S Veidal, Louise K D Fensholdt, Kristoffer T G Rigbolt, Henrik H Hansen, Li C Chen 2, Mathieu Petitjean 2 , Weslyn W Friley, Niels Vrang, Jacob Jelsing and Mark Young 1. - 1 Intercept Pharmaceuticals, San Diego, CA, USA - 2 PharmaNest Princeton, NJ

World J Gastroenterol 2018 January 14; 24(2): 195-210 - doi: 10.3748/wjg.v24.i2.195 - Weblink here

Clinical Journal of Gastroenterology and Hepatolohy | doi.org/10.1016/j.cgh.2019.09.050 - here

UPCOMING AND PAST CONFERENCE PRESENTATIONS

Quantitative image analysis reveals podocytes effacement and kidney fibrosis in SDT fatty rats with impaired renal function by unilateral nephrectomy and salt supplement diet. François Briand1, Estelle Grasset1, Masami Shinohara2, Nicole Endlich3, Vedran Drenić 3, Li Chen4, Mathieu Petitjean4, Yasushi Kageyama2, Thierry Sulpice1

ISN-World Congress of Nephrology, April 13-16 2024 Poster here

Quantitative Image Analysis Reveals the Benefits of Dapagliflozin on Glomerulosclerosis, Podocytes Effacement and Kidney Fibrosis in the SDT Fatty Rat Model of Diabetic Nephropathy. François Briand1, Estelle Grasset1, Masami Shinohara2, Nicole Endlich3, VedranDrenić3, Li Chen4, Mathieu Petitjean4,Blazej Dolicki5, Thomas de Bel5, Yasushi Kageyama2, Thierry Sulpice1 1Physiogenex, Escalquens, France, 2CLEA Japan Inc., 1–2–7 Higashiyama, Meguro-ku, Tokyo 153-8533, Japan, 3NIPOKA GmbH, Walther-Rathenau-Str. 49A, 17489 Greifswald, Germany, 4PharmaNest, 100 Overlook Center Princeton, NJ 08540 – USA 5Aiosyn, Toernooiveld 300, 6525 EC Nijmegen, The Netherlands.

CKD Summit 2024, Poster here

Cancer-associated fibroblast-specific expression of the matricellular protein CCN1 coordinates neovascularization and stroma deposition in melanoma metastasis. James Hutchenreuther, John Nguyen, Katherine Quesnel, Krista M. Vincent, Louis Petitjean, Sophia Bourgeois, Mark Boyd, George Bou-Gharios, Lynne-Marie Postovit, Andrew Leask. University of Saskatchewan, University of Western Ontario, University of Alberta, Queens University

Keystone Fibrosis and Inflammation, March 3-9 2024, March 2024: Poster Here

Digital Pathology Image Analysis Accurately detects the Anti-Fibrotic effects of Gene Therapy in Mouse Models of Duchenne Muscular Dystrophy. Adi Lightstone (1), Eun Young Jeon (2), Murim Choi (2), Li Chen (1), (1)PharmaNest, Princeton, NJ, USA, (2) Division of Biomedical Sciences, Seoul University, Korea

Keystone Fibrosis and Inflammation, March 3-9 2024, Poster Here

Novel digital pathology quantifies peripapillary fibrosis in mitral valve prolapse. Jordan Morningstar(1), Louis Petitjean(2), Li Chen(2), Russel Norris(1). (1) Medical University of South Carolina (2) PharmaNest, Inc

Keystone Fibrosis and Inflammation, Poster Here

Digital Pathology Accurately Quantifies Skin Fibrosis Severity in SPAG17 Gene Knockout Animal Model. Nathan Aist (1) Maria Teves (2), John Varga(3), Li Chen(1). (1) PharmaNest, Princeton, NJ, USA; (2) Virginia Commonwealth University, Richmond, VA, USA; (3) University of Michigan, MI, USA

Keystone Fibrosis and Inflammation, March 3-9 2024, Poster Here

Artificial intelligence-assisted digital pathology characterizes the fibrosis phenotypes in Cardiomyopathy. Adi Lightstone (1), Junedh Amrute (2), Kory Lavine (2), Li Chen (1). (1) PharmaNest, Princeton, NJ, USA; (2) Washington University, Center for Cardiovascular Research, St. Louis

Keystone Fibrosis and Inflammation, March 3-9 2024, Poster Here

2084-A | Novel artificial intelligence-assisted digital pathology quantitative image analysis predicts the occurrence of liver-related clinical events in the multicentric, European, Hepatic OuTcomes and SURvival Fatty Liver Registry (HOTSURFR) study. In collaboration with Pr. Vlad Ratziu and the European HOTSURF Investigators Team.

AASLD 2023, November 10-14 2023, AASLD 2023 Poster of Excellence here

Summary: The retrospective FibroNest Digital Pathology analysis of liver biopsies of 403 patients with NASH and 18 years of follow up (from the HOTSURF Registry) demonstrates that the Ph-FCS can predict the first liver related clinical events with an AUROC of 0.76. This proof-of-concept study sets the stage for a validation study in a much larger retrospective cohort.

2412-C Novel Digital Pathology quantitative image analysis and AI method detects traits of fibrosis treatment response. In collaboration with Bristol-Myers Squibb and Pr. Arun Sanyal at Virginia Commonwealth University

AASLD 2023, November 10-14 2023, AASLD 2023 Poster of Excellence here.

Summary: Using the Digital Pathlogy Images from the FACON1 study of pegbelfermin in 197 pre-cirrhotic NASH Patients, FibroNest identified twenty six histological traits of fibrosis that exhibit a statistically significant change from the treatment arms groups (vs Placebo). The related Treatment Engagement composite continuous score detects the antifibrotic effect of PGBF treatment with moderate performance as seen for similar outcomes (Histology, fibrotic biomarkers) reported for this study.

2038-A | Digital Pathology quantitative image analysis and AI method detects the treatment effect of pegbelfermin in Cirrhosis patients with a performance that benchmarks manual histological assessment. In collaboration with Bristol-Myers Squibb and Pr. Arun Sanyal at Virginia Commonwealth University.

AASLD 2023, November 10-14 2023, Poster here.

Summary: In the context of the FALCON2 study of pegbelfermin in Cirrhotic patients (145 patients with paired biopsies) FibroNest Quantitative digital pathology image analysis and AI generates a continuous score for fibrosis severity that enhances conventional histological staging, resolves the continuum of cirrhosis, classifies F3 from F4/Cirrhotic patients and identifies responders with a performance that benchmarks NASH-CRN and Ishak staging systems

2343-C | Mannose attenuates hepatic steatosis in a mouse NAFLD/NASH model and hepatocytes in vitro through modulation of Khk expression. In collaboration with Icahn School of Medicine at Mount Sinai and Pr. Jaime Chu

AASLD 2023, November 10-14 2023, Poster here.

Summary: findings uncover mannose as a novel therapeutic for NAFLD/NASH, possibly acting through modulation of fructose metabolizing pathways. Biological effects and detailed quantification of histological macrosteatosis substantiate different pathways for steatosis reduction. Ongoing studies will test the role of mannose and KHK in liver steatosis.

2400-C | Artificial Intelligence based digital pathology reveals fatty acid synthase (FASN) inhibitor alone or in combination with semaglutide improves fibrosis in diet-induced obese NASH mice. In collaboration with SAGIMET Biosciences and Gubra ApS.

AASLD 2023, November 10-14 2023, Poster Here

Summary: Combination treatment of FASN inhibitor and semaglutide showed further histological improvement on NAS and fibrosis compared to the single agent treatment in a mouse model of NASH, supporting future clinical evaluation of denifanstat/GLP-1 combination therapy.

4224-A | Transposon-based Oncogenes Integration in AbcB4(Mdre2)-/- mice recapitulates high susceptibility to Cholangiocarcinoma in Primary Sclerosing Cholangitis. In collaboration with Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA and Pr Yury Popov.

Conclusion: We established a new high-fidelity cholangiocarcinoma model in mice, termed SB CCA.Mdr2-/-, which recapitulates the increased susceptibility to CCA in the setting of progressive biliary injury and fibrosis observed in PSC. Furthermore, pharmacological targeting of ALK5 in our model suggests that TGFβ signaling functionally drives CCA tumorigenesis and promotes desmoplastic reaction.

PRESENTED AT THE 2023 INTERNATIONAL LIVER MEETING - EASL 2023, JUNE 21-24, 2023

Novel artificial intelligence-assisted digital pathology quantitative image analysis predicts the occurrence of liver-related clinical events in the multicentric, European, Hepatic OuTcomes and SURvival Fatty Liver Registry (HOTSURFR) study. In collaboration with Pr. Vlad Ratziu and the European HOTSURF Investigators Team.

Poster here

Summary: The retrospective FibroNest Digital Pathology analysis of a selection of liver biopsies from the HOTSURF Registry demonstrates that the Ph-FCS can predict liver related clinical events with an AUROC of 0.76. This proof-of-concept study sets the set for the validation of this results in a much larger retrospective cohort.

Evaluation of the performance of a novel single-nuclei Digital Pathology method for the continuous quantification of Steatosis and Inflammation in liver biopsies and its correlation with NASH-CRN scores in patients with NASH. In collaboration with Pr. Arun Sanyal, Pr. Cynthia Behling an esteemed team of pathologists from the Universities of California.

Poster here

Summary: FibroNest analysis of H&E Digital Pathology images generates quantitative tissue panels (cell counts, normalized ratios, and morphometric analysis of related inflammatory clusters) that remove the subjective and semi-quantitative limitation of current histological “manual” methods n9NASH-CRN). Results from a balanced NASH Cohort and their correlation with NASH CRN stages and grades are discussed.

Digital Pathology Quantification of Cirrhosis Severity Continuum in Human HCV Liver Biopsies and its Correspondence with Laennec and Beijing stages. In collaboration with Pr. Maria Isabel Fiel and Icahn School of Medicine at Mount Sinai, New York, NY, USA

Poster here

Summary: From a retrospective cohort of 100 liver biopsies from 20 transplanted cirrhotic patients (5 biopsies in each liver), we study intra-liver variability of FibroNest Ph-FCS and the correspondence of the FibroNest scores with NASH CRN, LAENNEC and BEIJING scores for fibrosis severity and activity.

FRI-458 - Evaluation of histological differences between cirrhosis due to alcoholic related liver disease and non-alcoholic steatohepatitis using automated fibrosis phenotyping of liver histology. In collaboration with Prs Masanori Fukushima and Hisamitsu Miyaaki and team at Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Poster here

Summary: this study establishes that the phenotypes of fibrosis in cirrhotic patients with NASH and ASH are significantly different and describes key histological traits of difference. The related digital pathology biomarker diagnostic test exhibits an AUROC of 0.96.

Is the hepatic fibrosis histological phenotype in pre- and post-menopausal F2/F3 women the same? In collaboration with Pr. Manuel Romero Gomez and the SeLIVER Group, Seville, Spain

Poster here

Summary: this study explores the differences of the histological phenotype of liver fibrosis in pre- and post-menopausal women with NASH and moderate to severe fibrosis.

Evaluation of anti-fibrotic compounds effect in 3D human NASH model using quantitative digital pathology. In collaboration with Dr. Radina Kostadinova, and InSphero AG

Poster here

Summary: this abstracts describes the performance of Digital Pathology and FibroNest to quantify fibrosis in the context of in-vitro assay (3DNASH spheroids) for mid-throughput screening of antifibrotic compounds.

Semaglutide has beneficial effects on non-alcoholic steatohepatitis in Ldlr-/-.Leiden mice In collaboration with José A. Inia at the Netherlands Organization for Applied Scientific Research.

Poster here

Summary: this study discusses the effect of high-resolution Digital Pathology for the phenotypic quantification of fibosis and macro-steatosis histological features and their change with semaglutide in a rodent NASH model.

Artificial intelligence based digital pathology reveals fatty acid synthase (FASN) inhibitor alone or in combination with semaglutide imrpooves fibrosis in diet-induced obese mice with biopsy confirmed NASH and fibrosis. Wen-Wei Tsai1, Mie Berke2, Michael Feigh2, Louis Petitjean3, Li Chen3, Eduardo B Martins1, George Kemble1, Marie O’Farrell1 1. Sagimet Biosciences, Inc, San Mateo, CA, USA, 2. Gubra ApS, Horsholm, Denmark, 3. PharmaNest, Inc, Princeton, NJ, USA . Poster here

PAST SCIENTIFIC PUBLICATIONS:

Breakthroughs in therapies for NASH and remaining challenges, Vlad Ratziu, Sven Francque, Arun Sanyal,

Journal of Hepatology 2022 vol. 76 j 1263–1278

International Journal of Molecular Sciences. 2023; 24 (10):8494. | doi.org/10.3390/ijms24108494

Science Translational Medicine, 4 Jan 2023, Vol 15, issue 677 | DOI: 10.1126/scitranslmed.add3949

Conclusion: Nonalcoholic steatohepatitis (NASH) has no approved therapy and advanced, fibrotic stages of the disease are in particular difficult to target. Wang et al. show that in both human and murine NASH, a profibrotic autocrine signaling loop comprising dozens of receptor-ligand pairs emerges in hepatic stellate cells specifically during late-stage disease. Pharmacological targeting of one of these receptor-ligand interactions reduced advanced fibrosis in a NASH mouse model, establishing this interaction as an antifibrotic target and suggesting the possibility of a disease stage-specific treatment.

PRESENTED AT KEYSTONE-FIBROSIS-NASH 2023

Contribution of Digital Pathology and AI to the quantification of fibrosis in Crohn’s disease. Li Chen1,Miha Jerala2, Nina Zidar2, Mathieu Petitjean1 PharmaNest, Inc, Princeton, New J, USA, 2Faculty of Medicine, Institute of Pathology, University of Ljubljana, Ljubljana, Slovenia

Poster here

Conclusion: The high-resolution (FibroNest) quantification of the histological phenotype of fibrosis and non-fibrotic tissue in each layer of the bowel wall provides significant insights into the histological hallmarks and pathogenesis of fibrosis in IBD, particularly of fibrostenosing CD. The severity scores could be used to distinguish among various forms of IBD, such as UC, CD with inflammatory stenosis and CD with fibrostenosis in the surgical specimens of IBD patients.

Digital Pathology Image Analysis Accurately Quantifies the Anti-Fibrotic and Anti-Steatotic effects of Mannose in a Well-validated Murine NASH Model. Li Chen1, Yvette Carbajal2, Charles DeRossi2, Scott Friedman3, Jaime Chu2, Mathieu Petitjean1 1 PharmaNest, Princeton, NJ, USA; 2Division of Pediatric Hepatology, Icahn School of Medicine at Mount Sinai New York, NY, USA; 3 Division of Liver Diseases, Icahn School of Medicine at Mount Sinai New York, NY, USA

Poster Here

Conclusion: Mannose has both anti-steatotic and anti-fibrotic effects during prophylactic and therapeutic treatments for experimental Nonalcoholic Steatohepatitis. FibroNestTM provides robust quantitative digital pathology measurements of fibrosis (and steatosis) severity and NASH regression in assessing compounds or pharmacological agents.

Comparison of the Histological Phenotypes of Lung Fibrosis induced by Oropharyngeal and Subcutaneous Bleomycin Administration in Mouse. Louis Petitjean1, Joline Attema2, Christa de Ruiter2, Reinout Stoop2, Li Chen1 1 PharmaNest, Princeton, NJ, USA 2 TNO, Netherlands Organization for Applied Scientific Research, Leiden, Netherlands

Poster Here

Conclusions: Quantitative Digital Pathology (FibroNest) of stained lung sections was able to quantify and compare the histological phenotypes of fibrosis in OP+SC and OP administration methods of Bleomycin in mouse. OP administration was shown to be more aggressive and rapid whereas OP+SC elicited a milder but more continuous response from the model. Furthermore, FibroNest was able to identify differences in fibrosis phenotypes between the two models.

Evaluation of the performance of a novel Digital Pathology score for the evaluation of Fibrosis in patients with Sjögren’s syndrome. Li Chen1, Ben Fowler2, Justin Willige2, Mathieu Petitjean1, Darise-Farris2, Kathy Sivils3 1PharmaNest, Princeton, NJ, USA | 2Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK | 3Janssen Pharmaceuticals, Inc, Horsham, PA.

Poster Here

Conclusions: An automated scoring system of the fibrosis histological phenotype has been developed. This scoring system can differentiate both Sjogren’s and non-SS sicca minor salivary glands from healthy control minor salivary glands. The scoring will be useful for investigating patient heterogeneity and fibrotic pathology in Sjogren’s and perhaps also some individuals with non-SS sicca.

Single-fiber Digital Pathology Image Analysis accurately quantifies the severity of the fibrosis phenotype in an experimental rodent model of systemic sclerosis. Silvia Speca1, Manel Jendoubi1, Thomas Guerrier1, Alexis Largi1, Li Chen2, Louis Petitjean2, Frédéric De Ceuninck3, Mathieu M. Petitjean2, David Launay 1,4 1Univ. Lille, Inserm, CHU Lille, U1286- INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France. 2Pharmanest, Inc, Princeton, NJ, US 3Institut de Recherche Servier, Neurology and immuno-inflammation therapeutic area, 78290 Croissy-sur-Seine, France 4CHU Lille, Service de médecine interne et immunologie clinique, Centre de référence des maladies auto-immunes systémiques rares du Nord et Nord-Ouest de France (CeRAINO), 59000 Lille, France

Poster Here

Conclusions: The FibroNest quantification of the histological fibrosis phenotype in complex tissues such as skin is a highly sensitive method capable of quantifying the content but also the shape and structural changes of the collagen. Skin Ph-FCS might be a relevant readout in future studies on pathophysiology and drug candidate assessment.

PRESENTED AT AASLD 2022 (links to the posters will be embedded after the conference)

Histologic assessments by Pathologists and Digital Pathology describe the antifibrotic effect of LPCN 1144. Li Chen, Benjamin J. Bruno, Nachiappan Chidambaram, Cynthia Behling, Mathieu M. Petitjean, Arun J. Sanyal

Link to poster here

Conclusion: Results of this proof-of-concept study support potential antifibrotic effects of LPCN 1144. Both ranked assessments and AI evaluations identified more subjects with fibrosis improvement than the current FDA primary outcomes needed for interim approval. In partnership with Lipocine, Inc.

Quantitative Digital Pathology and Imaging methods demonstrate the consistent reduction of liver fat burden in patient treated with LPCN 1144. Li Chen, Benjamin J. Bruno, Nachiappan Chidambaram, Cynthia Behling, Mathieu M. Petitjean, Arun J. Sanyal

Link to poster here

Conclusion: LPCN 1144, both alone and in combination with d-alpha tocopherol, demonstrates a strong antisteatotic effect. Digital Pathology and Imaging methods for the continuous assessment of these effects are highly correlated and provide a robust support of the pathologist-based results. In partnership with Lipocine, Inc.

Digital Pathology Quantification of Intra(“geographic”)-Liver Variation in Human HCV Cirrhosis Liver Biopsies. Louis Petitjean, Xiaofei Zhang, Maria Isabel Fiel, Thomas Shiano, A. J. Sanyal, Mathieu Petitjean

Link to poster here

Conclusion: FibroNest’s was able to quantify the severity of fibrosis from moderate NASH fibrosis levels to complex phenotypes within the HCV Cirrhosis spectrum. The average intra(“geographic”)-liver Ph-FCS variability was 16.6±1.3. This is significantly smaller than previously reported CoVs of 47.3±4.5%, observed on collagen proportionate area (CPA) due to the comprehensive scope of measurements that form the Ph-FCS. In partnership with Mount Sinai Medical School.

An autocrine signaling circuit in hepatic steallate cells underlies advanced fibrosis in non-alcoholic steatohepatitis. Shuang Wang, Kenneth Li, Eliana Pickholz, Ross Dobie, Neil C. Henderson, Christopher Carrico, Ian Driver, Martin Borch Jensen, Li Chen, Mathieu M. Petitjean, Dipankar Bhattacharya, Xiao Liu, Tatiana Kisseleva, Uri Alon, Miri Adler, Ruslan M Medzhitov and Scott L. Friedman.

Conclusion: As NASH progresses, a unique physical and molecular HSC autocrine circuitry emerges that drives late-stage fibrosis in murine and human disease. Drivers of this autocrine crosstalk represent a repertoire of previously uncharacterized antifibrotic drug targets and suggest that effective therapy for advanced NASH fibrosis may need to engage unique targets that are distinct from earlier-stage disease. In partnership with Mount Sinai Medical School.

Semaglutide has beneficial effects on Non-Alcoholic steatohepatitis in LDLR-/-. Leiden Mice. José A Inia, Geurt Stokman, Elsbet J. Pieterman, Martine Morrison, Nicole Worms, Lars Verschuren, Martien P.M. Caspers, Aswin L., Menke, Mathieu M. Petitjean, Louis Petitjean, Li Chen, J. Wouter Jukema, Hans Princen and Anita M. Van Den Hoek.

Conclusion: A translational mice model with advanced NASH was used to demonstrate that semaglutide is a promising candidate with particular potential for the treatment of hepatic steatosis and inflammation, while for reversal of more advanced fibrosis, probably combinations with other NASH agents will be necessary. In partnership with The Netherlands Organization for Applied Scientific Research (TNO)

ALREADY PUBLISHED:

Multimodality assessment of hepatic fibrosis: Ranked paired reading and artificial intelligence identifies fibrosis improvement with Aramchol missed by conventional staging. V. Ratziu, Y. Yilmaz, D. Lazas, S.L. Friedman, C. Lackner, C. Behling, OW. Cummings, Li Chen, M. Petitjean, Y. Gilgun-Sherk, S. Kadosh, and A. J. Sanyal

See poster here

Conclusion: Aramchol resulted in a high proportion of fibrosis improvement using three separate biopsy reading methodologies, with a larger treatment effect with longer duration of therapy. Both ranked assessments and AI evaluations identified more subjects with fibrosis improvement, indicating greater sensitivity to change vs categorical scoring. Digital pathology quantification by AI reveals a high level of fibrosis improvement that would have been missed by conventional histological measurements. AI technologies are promising for the detection of fibrosis changes in future clinical trials.

Novel Digital Pathology quantitative image analysis and AI method detects the treatment effect of NASH drug candidates with a performance that benchmarks Imaging based measurements. Li Chen (1), Elizabeth Brown (2), Anne Minnich (2), Vipul Baxi (2), Dimple Pandya (2), Edgar D. Charles (2), Zachary Goodman (3), Shuyan Du (2), Mathieu Petitjean (1), Arun J. Sanyal (4), (1) Pharmanest, Princeton, NJ, USA (2) Bristol Myers Squibb, Princeton, NJ, USA (3) Inova Health Systems, Falls Church, VA (4) Virginia Commonwealth University, Richmond, VA, USA

See Poster here

Conclusion: Combined to AI algorithms, quantitative digital pathology image analysis generates continuous scores that enhance conventional histological staging methods. They detect the antifibrotic and anti-steatosis effect of treatment such as PGBF with a performance that benchmarks imaging-based measurements.

Evaluation of the performance of a novel Digital Pathology method for the continuous quantification of Steatosis, Ballooning and Inflammation in liver biopsies and its correlation with NASH-CRN scores in patients with NASH. Louis Petitjean (1), Li Chen (1), Aras N. Mattis (2), Mojgan Hosseini (3), Michael Goedken (4) , Cynthia Behling (5), Arun J. Sanyal (6), Mathieu Petitjean (1)- (1) Pharmanest, Princeton, NJ, USA, (2) Department of Pathology, University of California San Francisco, San Francisco, CA, (3) Department of Pathology, University of California, San Diego, California, USA, (4) Rutgers Research Pathology Services, New Brunswick, NJ USA, (5) Department of Pediatrics University of California, San Diego, CA, USA, (6) Virginia Commonwealth University, Richmond, VA, USA.

See poster here

Conclusion: As reported by other teams, liver biopsy Digital Pathology methods based on supervised ML and annotation provided by pathologists (H&E stains, Inflammation, Ballooning) result in continuous quantification methods of moderate performance.

Etiology-independent fibrosis severity scoring by quantitative digital pathology image analysis. Adam Watson EASL2022 Young Scientist Scholarship Award (1), Louis Petitjean (2), Michael Pavlides(1), Mathieu Petitjean (2) – (1) Medical Sciences Division, University of Oxford, Oxford, UK, Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK, (2) Pharmanest, Princeton, NJ, USA

See poster here

Conclusion: Our data shows that quantitative digital pathology image analysis can phenotype fibrosis and quantify severity in multiple liver disease aetiologies. We used this technology to develop an etiology-independent score to assess the severity of fibrosis from liver biopsies.

Advanced quantitative phenotypic fibrosis and steatosis scoring is markedly superior to histology-based conventional staging in NASH animal models. Li Chen (1) , Dipankar Bhattacharya (2), Scott Friedman (2), Mathieu Petitjean (1) – (1) PharmaNest, Princeton, NJ, USA (2) Division of Liver Diseases, Icahn School of Medicine at Mount Sinai New York, NY, USA

See poster here

Conclusion: FibroNest shows a markedly wider dynamic range of differences between the groups in the FAT-NASH study. This allows greater detection and sensitivity for subtle changes. FibroNest provides a more sensitive and reliable evaluation of fibrosis severity and progression in NASH and for the evaluation of therapeutic drug efficacy.

Translational Fibrosis Phenotypes between the 3D Human NASH Spheroidal Model and Clinical NASH Samples. Louis Petitjean (1), Simon Strӧbel (2), Li C. Chen (1), Fancisco Verduguer (2), Radina Kostadinova (2), Arun J. Sanyal(3) – (1) PharmaNest, Princeton, NJ, USA (2) InSphero AG., Schlieren, Switzerland (3) Virginia Commonwealth University, Richmond, VA, USA

See poster here

Conclusions: We identified 97 histological traits of fibrosis severity phenotype that can be translated from the 3D NASH spheroid model to clinical F2 or F3 NASH CRN stages. These traits will be used to evaluate the anti-fibrotic compounds effect in 3D NASH model to predict their effect in human.

Quantitative digital Pathology of 3D human NASH models establish continuous scores to evaluate the antifibrotic effects of Selonsertib, Firsocostat and Resmetiron. Louis Petitjean (1)- EASL2022 Young Scientist Full Scholarship Award, Simon Strӧbel (2) , Li C. Chen (1), , Eva Thoma (2), Radina Kostadinova (2)- (1) PharmaNest, Princeton, NJ, USA (2) InSphero AG, Schlieren, Switzerland.

See poster here

Conclusion: The combination of FibroNestTM imaging analysis for automated quantification of histological fibrosis severity phenotype within vitro 3D InSightTM human NASHmodel provide powerful platform for anti-fibrotic drug-candidates response evaluation.

3D human NASH model as a screening-based discovery approach for selecting and prioritizing drug candidates. Simon Ströbel (1), Jana Rupp (1), Katia Fiaschetti (1), Agnieszka Pajak (1), Katarzyna Sanchez (1), Mathieu Petitjean (2), Li Chen (2), Manuela Bieri (1), Armin Wolf (1), Sue Grepper (1), Francisco Verdeguer (1), Radina Kostadinova (1), 1 - InSphero AG., Schlieren, Switzerland , 2- PharmaNest, Princeton, NJ, USA

KEYSTONE FIBROSIS 2022

Advanced Skin Image Analysis for Evaluation of Bleomycin- induced Skin Fibrosis in Mouse Scleroderma Model. Li Chen (1), Louis Petitjean (1), Christa de Ruiter (2), Joline Attema (2), Reinout Stoop (2), Li Chen (1) | 1 -PharmaNest, Princeton, NJ, USA | 2 - TNO, Netherlands Organisation for Applied Scientific Research, Leiden, Netherlands

Presented at Keystone Fibrosis and Inflammation 2022 (Poster Here)

Describing the Progression of Bleomycin-Induced Fibrosis in a Mouse-Lung Model via Oropharyngeal Administration. Louis Petitjean (1), Christa de Ruiter (2), Joline Attema (2), Reinout Stoop (2), Li Chen (1) | 1 -PharmaNest, Princeton, NJ, USA | 2 - TNO, Netherlands Organisation for Applied Scientific Research, Leiden, Netherlands

Presented at Keystone Fibrosis and Inflammation 2022 (Poster Here)

NASH-TAG 2022

Ex-vivo human 3D NASH model as a screening-based discovery approach for selecting and prioritizing drug candidates. Simon Ströbel(1), Jana Rupp(1), Katia Fiaschetti(1), Agnieszka Pajak(1), Katarzyna Sanchez(1), Louis Petitjean(2), Li Chen(2), Manuela Bieri(1), Armin Wolf(1), Sue Grepper(1), Francisco Verdeguer(1), Eva Thoma(1), Radina Kostadinova(1), (1): InSphero AG, Schlieren, Switzerland, (2): PharmaNest, Princeton, USA

Presented at NASH-TAG 2022 (Abstract here)

AASLD 2021

LPCN 1144 Therapy demonstrates Histologic Benefits in the Phase2 LiFT Study in NonAlcoholic Steatohepatitis (NASH) Subjects. Arun J Sanyal (1), Benjamin J Bruno (2), Kilyoung Kim (2), Shadi Mehraban (2), Kongnara Papangkorn (2), Anthony DelConte (2),(3), Nachiappan Chidambaram (2) and Mahesh V Patel (2), (1) Div of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, USA, (2)Lipocine Inc., Salt Lake City, UT, USA, (3) Department of Pharmaceutical/Healthcare Marketing, Saint Joseph's University, Philadelphia, PA, USA

Presented at AASLD 2021 (Late Breaker abstract LP41)

Is the histological phenotype of Fibrosis different between LEAN and OBESE NASH patients? Michihiro Iwaki (1), Li Chen (2), Mathieu Petitjean (2), Atsushi Nakajima (1), Vincent Wai-Sun Wong (3) - (1) Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Japan (2) Pharmanest Inc, Princeton, New Jersey, USA (3) Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong

Presented at AASLD 2021, #1704 (Poster here)

Evaluation of the multivendor performance of a novel histology-based fibrosis phenotypic composite score and its correlation with NASH-CRN Fibrosis scores in patients with NASH Li Chen (1), Michael Lung (2), Cynthia Behling (3), Anthony Azzara (4), Diane Shevell (4), Arun J. Sanyal (5), Mathieu Petitjean (1) - (1) Pharmanest, Princeton, NJ, USA (2) Pacific Rim Pathology, San Diego, CA, USA (3) Department of Pediatrics University of California, San Diego, CA, USA (4) Bristol Myers Squibb, Princeton, NJ, USA (5) Virginia Commonwealth University, Richmond, VA, USA

Presented at AASLD 2021, #1601 (Poster Here)

Combination of an Acetyl-CoA Carboxylase Inhibitor and Fibroblast Growth Factor-19 Reduced Tissue Triglyceride Content and Fibrosis in a 3D Human Liver Microtissue Model of Nonalcoholic Steatohepatitis. Wen-Wei Tsai,1 Manuela Bieri,2 Sue Grepper,2 Eva Thoma,2 James L. Trevaskis1 -1 Gilead Sciences Inc., Foster City, CA; 2 InSphero AG, Schlieren, Switzerland

Presented at AASLD 2021, #1621 (Poster Here)

FG19 Gene therapy reduces Steatosis but not Inflammation and Fibrosis in Two Mouse Models of NASH – Martin Borch Jensen, Chris Carrico, Linda Chio, Ian Driver, Daniel Fuentes, Akela Kuwahara, Francisco LePort, Chris Towne. Gordian Biotechnology.

AASLD 2021 Poster Here.

Therapeutic Candidates in a single Animal Model of NASH Martin Borch Jensen, Chris Carrico, Linda Chio, Ian Driver, Daniel Fuentes, Akela Kuwahara, Francisco LePort, Chris Towne- Gordian Biotechnology, San Francisco, CA –

AASLD 2021 Poster Here

In-Vitro human 3D NASH model as a screening-based discovery approach for selecting and prioritizing drug candidates. Simon Strӧbel, Jana Rupp, Katia Fiaschetti, Agnieska Pajat, Katarzyna Sanchez (1), Mathieu M. Petitjean, Li Chen (2), Manuela Bieri, Armin Wolf, Sue Grepper Eva Thoma, Radina Kostadinova (1). (1) InSphero AG, Schlieren, Switzerland (2) PharmaNest, Princeton, NJ, USA

Presented at AASLD 2021, #1906 (Poster Here)

Digital Pathology Image Analysis Accurately Quantifies Anti-fibrotic and Anti-steatotic effects of FXR Agonists Using Multiple Histological Methods. Li Chen (1), Mary Erickson (2), Luciano Adorini (2), Jonathan Roth (2), Mathieu Petitjean (1)- 1 PharmaNest, Princeton, NJ, USA, 2 Intercept Pharmaceuticals, San Diego, CA, USA

Presented at AASLD 2021, #1908 (Poster Here)

Continuous staging of NASH Patients at low (F1) Fibrosis Severity: Evaluation of the performance of a novel histology-based fibrosis phenotypic composite score and predictive AI tools. Li Chen (1), Dmitry Fedorov (2), Mathieu Petitjean (1), Benjamin J. Bruno (3), Kilyoung Kim (3), Cynthia Behling (4), Anthony DelConte (5), Nachiappan Chidambaram (3) - (1) Pharmanest Inc, Princeton, New Jersey, USA (2) ViQi Inc, Santa Barbara, California, USA (3) Lipocine Inc. Salt Lake City, Utah, USA (4) Pacific Rim Pathology, San Diego, CA, USA (5) Saint Joseph’s University, Philadelphia, PA, USA

Presented at AASLD 2021, #1587 (Poster Here)

SB CCA.Mdr2-/-, a new mouse model of Cholangiocarcinoma arising in the PSC-like settings of progressive biliary injury and fibrosis. Pinzhu Huang1, Guangyan Wei 1, Shuangshuang Zhao1, Disha Badlani1, Kahini Vaid1, Li Chen2, Mathieu Petitjean2, Xin Chen3, Gregory Gores4, Yury Popov1 - (1) Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, (2) PharmaNest, Inc, Princeton, NJ, (3) University of California, san Francisco, CA and (4) Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN

To be presented in-person at AASLD 2021 (Poster #1183)

Evaluation of anti-fibrotic effects of compounds in human 3D NASH model using phenotypic quantification of fibrosis digital pathology images. Li Chen (1) ,Simon Strӧbel (2) , Mathieu M. Petitjean (1), Eva Thoma (2), Radina Kostadinova (2) (1) PharmaNest, Princeton, NJ, USA (2) InSphero AG, Schlieren, Switzerland

Presented at AASLD 2021, #1362 (Poster Here)

A rapid 3D in Vitro Screening-based discovery approach for selecting and prioritizing NASH drug Candidates. Simon Ströbel (1), Radina Kostadinova(1),Jana Rupp(1), Katia Fiaschetti(1), Agnieszka Pajak(1), Katarzyna Sanchez(1), Mathieu Petitjean(2), Li Chen(2), Manuela Bieri(1), Armin Wolf(1), Eva Thoma(1) - (1)InSphero AG, Schlieren, Switzerland; (2)PharmaNest, (1)00 Overlook, Princeton, NJ 08540, USA

Poster # PO-2210

New mouse model of cholangiocarcinoma arising in the setting of progressive biliary injury and fibrosis. Pinzhu Huang (1), Guangyan Wei (1), Shuangshuang Zhao (1), Disha Badlani (1), Kahini Vaid (1), Li Chen (2), Mathieu Petitjean (2), Xin Chen (3), Gregory Gores (4), Yury Popov (1) (1) Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, (2) PharmaNest, Inc, Princeton, NJ, (3) University of California, San Francisco, CA and (4) Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN

Poster # PO-677 Here

Novel Phenomics NASH In Vitro Assay Presented by InSphero AG and PharmaNest Inc at 2021 Society of Toxicology Meeting. Radina Kostadinova 1, Mathieu Petitjean 2, (1) InSphero AG, Schlieren, Switzerland, (2) PharmaNest Inc, Princeton, NJ, USA

Elafibranor improves diet-induced nonalcoholic steatohepatitis associated with heart failure with preserved ejection fraction in Golden Syrian hamsters. François Briand 1, Julie Maupoint 2, Emmanuel Brousseau 1, Natalia Breyner 1, Mélanie Bouchet 1, Clément Costard 2, Thierry Leste-Lasserre 4, Mathieu Petitjean 5, Li Chen 5, Audrey Chabrat 6, Virgile Richard 6, Rémy Burcelin 7, Caroline Dubroca 2, Thierry Sulpice 1. (1) Physiogenex, 280 rue de l'Hers, ZAC de la Masquère, 31750 Escalquens, France, (2) Cardiomedex, 280 rue de l'Hers, ZAC de la Masquère, 31750 Escalquens, France, (4) Neurocentre Magendie, 146 rue Léo Saignat, 33077 Bordeaux cedex, France, (5) PharmaNest, 100 Overlook Center, FL2, Princeton, NJ 08540, United States of America, (6) Sciempath Labo, 7 rue de la Gratiole, 37270 Larcay, France (7) Inserm U1048 CHU Rangueil, BP 84225, 31432 Toulouse Cedex 4, France.

Metabolism. 2021 Jan 11;117:154707. (Online Here)

Automated Fibrosis Phenotyping of NASH non-tumorous lesions Digital Images Helps Classify HCC and non-HCC NASH patients who underwent liver transplantation. Hisamitsu Miyaaki1, Yuko Akazawa1 , Li Chen2, Mathieu Petitjean2 (1) Nagasaki University, Nagasaki, Japan (2) PharmaNest, Princeton, NJ, USA

Presented at AASLD 2020 (Poster here)

Novel phenotypic image analysis of 3D NASH model generate quantitative and continuous scores for the evaluation of fibrosis in vitro. Mathieu M. Petitjean1, Radina Kostadinova2, Li Chen1, Simon Strӧbel2, Eva Thoma2 (1) PharmaNest, Princeton, NJ, USA (2) InSphero AG, Schlieren, Switzerland

Presented at AASLD 2020 (Poster here)

Evaluation of a novel histology-based fibrosis phenotypic composite score and its correlation with NASH-CRN Fibrosis scores in patients with NASH. Li Chen (1), Michael Lung (2), Cynthia Behling (2), Arun Sanyal (3), Mathieu Petitjean (1). 1 - PharmaNest, Princeton, NJ, USA; 2- University of California, San Diego, NAFLD Research Center, Division of Gastroenterology. 3-Virginia Commonwealth University, Richmond, VA, USA.

Presented at EASL2020 (Poster here)

Microscopy‐based fibrosis phenotypic analysis of rodent and adult NASH cohorts reveal translational traits of fibrosis progression and severity. Li Chen (1), Anthony Azzara (2), Mathieu Petitjean (1), Arun Sanyal (3) - 1-PharmaNest, Princeton, NJ, USA; 2-Bristol-Myers Squibb Company, Princeton, NJ, USA 3-Virginia Commonwealth University, Richmond, VA, USA.

Presented at EASL2020 (Poster here)

Fibrosis phenotypic analysis of collagen stained liver histology sections discern anti-fibrotic agents in DDC- induced cholangitis mouse model. Li Chen (1), Richard Chen (2), Liangsu Wang (2), Mathieu Petitjean (1), 1-Pharmanest, Princeton, NJ, USA; 2-Morphic Therapeutic, Waltham, MA, USA

Presented at EASL2020 (Poster here)

Novel morphometric image analysis of idiopathic pulmonary fibrosis models generates quantitative and continuous scores for the evaluation of fibrosis. Florence Marsais (1), Li Chen (2), Mathieu Petitjean (2), Philippe Pujuguet (1), (1) Galapagos SA, Romainville, France, (2) PharmaNest, Princeton, NJ, USA, presented at 2020 Keystone Fibrosis and Tissue Repair, March 19-22 2020

Poster Here

Novel morphometric image analysis of Chronic Kidney Disease STNx model generates quantitative and continuous scores for the evaluation of fibrosis. Teodelina Mirabella (1), Matthew Rankin (1), Li Chen (2), Mathieu Petitjean (2), Matthew Bryer (1), (1) Janssen Pharmaceuticals, Boston, MA, USA, (2) PharmaNest, Princeton, NJ, USA. Presented at 2020 Keystone Fibrosis and Tissue Repair, March 19-22 2020

Poster Here

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. Li Chen 1, Yi Luo 2, Faridoddin Mirshahi 3, Anthony Azzara 2, Arun Sanyal 3, Mathieu Petitjean 1 - PharmaNest, Princeton, NJ, USA; 2 Bristol-Myers Squibb Company, Princeton, NJ, USA 3-Virginia Commonwealth University, Richmond, VA, USA. Poster presentation at AASLD 2019.

Poster Here

Development of an Optimal Continuous Pediatric Fibrosis Score to Assess Severity and Progression of Fibrosis in Non-alcoholic Fatty Liver Disease (NAFLD). Elena Reynoso 1, Li Chen 2, Mathieu Petitjean 2, Cynthia Behling 3, Joel Lavine 1 - 1 Pediatric Gastroenterology, Hepatology & Nutrition, Columbia Vagelos College of Physicians and Surgeons, New York, NY 2 - PharmaNest Princeton, NJ - 3 University of California, San Diego, NAFLD Research Center, Division of Gastroenterology. Poster presentation at AASLD 2019.

Poster Here

Automated Steatosis Morphometric Scores Benchmark the Pathology-Based Quantification of Steatosis in Pediatric NASH/NAFLD Populations. Zachary Pitkowsky 1, Li Chen 2, Elena Reynoso 1, Mathieu Petitjean 2, Cynthia Behling 3, Joel Lavine 1 - 1 Pediatric Gastroenterology, Hepatology & Nutrition, Columbia Vagelos College of Physicians and Surgeons, New York, NY 2 - PharmaNest Princeton, NJ - 3 University of California, San Diego, NAFLD Research Center, Division of Gastroenterology. Poster presentation at AASLD 2019.

Poster Here

Automated Morphometric Fibrosis Phenotyping of NAFLD Biopsies Digital Images Helps Classify NASH-Type 1 Vs NASH-Type 2 in Early Fibrosis Pediatric Patients. Mathieu Petitjean 1, Li Chen 1, Elena Reynoso 2, Cynthia Behling 3, Joel E. Lavine 2. - 1 PharmaNest Princeton, NJ - 2 Pediatric Gastroenterology, Hepatology & Nutrition, Columbia Vagelos College of Physicians and Surgeons, New York, NY - 3 University of California, San Diego, NAFLD Research Center, Division of Gastroenterology. Poster presentation at AASLD 2019.

Poster Here

Clinical Journal of Gastroenterology and Hepatolohy | doi.org/10.1016/j.cgh.2019.09.050 - here

Presented at EASL 2019 - Poster here

Morphometric collagen analysis discerns anti-fibrotic effects of INT-767 and OCA in NASH mouse models using second harmonic generation imaging. Li Chen 1, Mathieu Petitjean 1, Luciano Adorini 2, Jonathan Roth 2. 1 PharmaNest Princeton, NJ - - 2 Intercept Pharmaceuticals, San Diego, CA, USA

Presented at EASL 2019 - Abstract SAT-342 - Poster here.

ASK1 Inhibition Reduces Progression of Liver Cirrhosis and Prevents Tumor Development in the BALS/c.Mdr2-/- Mouse Model of Biliary Fibrosis. G. Wei 1, P. An 1, K, Vaid 1, G. Budas 1, A. Mikels-Vigdal 1 , M. Kuand, Y. Popov 2. - 1 Gilead Sciences, San Francisco, CA, USA - 2 Beth Israel Deaconess Medical Center, Boston, MA, USA

Presented at AASDL 2018. Poster here.

Quantitative Assessment of Liver Septal Fibrosis Severity Using Morphometric Analysis, Li Chen PhD1 ., Anthony Azzara PhD 2., Mathieu Petitjean PhD 1 ., Presented at NASH-TAG 2018. 1 PharmaNest Princeton, NJ - 2 Bristol Myers Squibb, Princeton, NJ , USA

Poster here

Second Harmonic Generation Imaging Microscopy quantifies and characterizes fibrosis in the bowell wall of ulcerative colitis resection - A pilot study. Florian Reider et all. To be presented at DDW 2018 - June 2-5 2018

New Standards in Fibrosis Quantification: the Value of Label-free Second Harmonic Generation. Li Chen, Mathieu Petitjean at the Anti-fibrotic Drug Development Forum, November 13-14, 2017, Boston USA

See slides from the podium presentation here

See poster here

World J Gastroenterol 2018 January 14; 24(2): 195-210 - doi: 10.3748/wjg.v24.i2.195 - Weblink here

Detailed Analysis of the Antifibrotic effect of INT-767, a dual FXR/TGR5 agonist in an obese mouse model of diet-induced and biopsy-confirmed NASH. Sanne Skovgård Veidal, Michael Feigh, Henrik B Hansen, Jacob Jelsing, Niels Vrang, Mathieu Petitjean, Li Chen, Mark Young, Jonathan Roth presented at AASLD 2017, October 20-23 , 2017.

See poster here (Presidential Award)

Novel Methods in Imaging and Quantification of Skeletal Muscle Fibrosis Associated with Severe Muscular Dystrophy. David W. Hammers, Coar C. Coker, Li Chen, Mathieu Petitjean, Elizabeth R. Barton, H.Lee Sweeney presented at Keystone Injury, Inflammation and Fibrosis, March 26-30 2017.

See poster picture here (poster PDF file to come)

Use of Second Harmonic Generation (SHG) and 2-Photon Emission Imaging to Quantify and Describe the Structure of Tissue Fibrosis in the Rat TNBS intestinal fibrosis model. Laura Johnson, Li.Chen, P. Higgings et all. Poster #2008 presented at Keystone Injury, Inflammation and Fibrosis, March 26-30 2017.

Poster Here

Concurrent Semi-Automated Quantification of Liver Fibrosis and Fat Using Label-free Second Harmonic Generation Imaging in Animal Models. M. Petitjean, J. Schwartz, Li Chen. Poster #3003 - presented at Keystone Injury, Inflammation and Fibrosis, March 26-30 2017

Poster Here

Quantification of Septa in Liver Fibrosis using Second Harmonic Generation Imaging. Li Chen, Mohammad Naser, et all. Poster #1016 - presented at Keystone Injury, Inflammation and Fibrosis, March 26-30 2017

Poster Here