Deciphering NASH: Fibrosis Dynamics in Cirrhotic Patients & Insights into Ballooned Hepatocytes Using AI

In partnership with:

PRESENTERS’ DETAILS & TOPICS:

Dr. Mazen Noureddin MD, MHSc
Director of Fatty Liver Program, Cedars-Sinai Medical Center, Los Angeles, California, USA

Dr Noureddin is the founding director of the Fatty Liver Program at Cedars-Sinai Medical Center (currently ranked #2 in GI and GI surgery per US News). Dr. Noureddin did his internal medicine residency at the University of Southern California (USC) and then moved to the National Institutes of Health (NIH), where he enrolled in a three-year hepatology fellowship at the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). There, he finished the NIH/Duke University Master of Health Sciences in Clinical Research program. After completing his NIH fellowship, he completed a gastroenterology fellowship at the University of California, San Diego (UCSD), where he was a T32 NIH fellow. He then joined the University of Southern California (USC) as an Assistant Professor of Clinical Medicine in 2013. He was then recruited to Cedars-Sinai Medical Center in 2015 to establish its new fatty liver program.

Dr. Noureddin is internationally known for his research in NAFLD/NASH and NASH-related cirrhosis. He conducted more than 40 investigational clinical studies of novel treatments for NASH. In addition, he is an expert in non-invasive testing and biomarkers of the field, especially serum biomarkers, trainset elastography, and magnetic resonance imaging techniques. He has published in all these areas and has been invited to consensus panels on this topic by multiple societies including the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of Liver Diseases (EASL). He has given invited lectures on NAFLD/NASH at national and international society meetings and serves on several steering committees/advisory boards for industry. He is the vice chair of the AASLD NASH special interest group (will be chairing the group in 2023) and serves on the editorial board for major GI journals including “Gastroenterology”, “Hepatology” and “Clinical Gastroenterology and Hepatology (CGH)”. He is one of the new Associate Editors of “Clinical Gastroenterology and Hepatology (CGH)” starting 2022. He is funded by the National Cancer Institute and has served as a reviewer on NIH study section. He has published in many journals including: The Lancet, Science Trinational Medicine, Journal of Hepatology, Journal of Clinical Investigation, Gastroenterology, Hepatology, Clinical Gastroenterology and Hepatology and others.

Presentation Topic: Quantitative Assessment of Septa, Nodules and Fibrosis (SNOF) using Stain-free AI Digital Pathology Shows Excellent Correlation with Portal Pressures and Varices in NASH Patients with Cirrhosis

This presentation will be based on the poster presentation at the AASLD’s The Liver Meeting 2021, titled, Development of Machine Learning Histological Scores that Correlated with Portal Pressures and Development of Varices in NASH patients with Cirrhosis.

Primary endpoints of NASH cirrhotic trials include hepatic venous pressure gradient (HVPG) and liver histology, and a reduction in HVPG and fibrosis improvement are associated with improved clinical outcomes. However, current histological scoring systems do not capture septum thickness and nodule size as part of fibrosis dynamics in NASH cirrhosis.

The study therefore examined if a machine learning (ML) algorithm could accurately predict HVPG and presence of varices from liver histology. Stain-free AI-DP with SHG/TPEF provided a quantitative assessment of septa, nodules, and fibrosis (SNOF), and ML scores were established to evaluate its association with HVPG and relevant features, as well as the presence of varices. This presentation reviews the correlations of the ML algorithm projections along with traditional methods and discuss the findings that indicate the potential of stain-free AI-DP with SHG/TPEF in improving accuracy of efficacy endpoints in NASH cirrhosis trials.

Prof. Quentin M. Anstee BSc(Hons), MB BS, PhD, MRCP(UK), FRCP
Chair of Experimental Hepatology and Consultant Hepatologist, Faculty of Medical Sciences, Newcastle University, UK; Honorary Consultant Hepatologist of the Liver Unit, Freeman Hospital, Newcastle, UK.

Prof Anstee is the Chair of Experimental Hepatology and the Deputy-Dean of Research & Innovation in the Faculty of Medical Sciences, Newcastle University, UK. A practicing clinician, he is also an Honorary Consultant Hepatologist in the Liver Transplant Unit at Newcastle’s Freeman Hospital, where he leads one of the largest Non-Alcoholic Fatty Liver Disease (NAFLD) clinical services in the U.K. He trained in medicine at University College London where he was awarded a First Class Honours degree and won First Prize in Medicine in the final MB BS examination.

Prof Anstee’s translational research has made major contributions across the pathophysiology, natural history, diagnosis and treatment of NAFLD. His work has provided key insights into temporal changes in steatohepatitis during disease evolution, identified genetic and epigenetic modifiers of liver disease progression and hepatocellular carcinoma risk, and has substantially advanced the field of biomarker development in liver disease. He coordinates two major international research consortia that are studying NAFLD pathogenesis and developing/validating accurate biomarkers to assist the diagnosis, risk-stratification and monitoring of patients with NAFLD: ‘EPoS’ Elucidating Pathways of Steatohepatitis (EU H2020 funded €6 million, 2015-2019) and ‘LITMUS’ Liver Investigation: Testing Marker Utility in Steatohepatitis (EU IMI2 funded €47.3 million, 2017-2022). He has established a pan-European NAFLD Registry and is the chief investigator of multiple ongoing clinical trials assessing new medical therapies for NAFLD. He is an Associate Editor of the Journal of Hepatology.

Presentation Topic: Development of Concordance Atlas for Stain-free AI Digital Pathology in Ballooned Hepatocyte Feature Recognition

This presentation will be based on the recently published Journal of Hepatology paper, titled, Complexity of ballooned hepatocyte feature recognition: Defining a training atlas for artificial intelligence-based imaging in NAFLD.

Histologically assessed hepatocyte ballooning is a key feature in discriminating nonalcoholic steatohepatitis (NASH) from steatosis (NAFL). For patient inclusion and treatment efficacy evaluation in clinical trials, there is a pressing need for reproducible, objective and standardized evaluation of the significant histopathological features that discriminate NAFL from NASH, in particular, the presence and quantification of hepatocyte ballooning.

The primary goals of the study were:
• To utilize input from blinded independent assessments by nine internationally recognized expert hepatopathologists to generate a dataset of reliably and reproducibly identified ballooned hepatocytes that can be used to support the development of machine learning with AI algorithms for the detection and quantification of hepatocyte ballooning; and,

• To conduct a focused study that accurately evaluated interobserver variation in hepatocyte ballooning feature recognition. Digitized slides were chosen because they are increasingly used in clinical trials and because only digitisation facilitates the necessary granular annotation of individual cells.

The findings from this study highlight the potential of training the stain-free AI-DP with SHG/TPEF with a guided ‘Concordance Atlas’ to quantify ballooned hepatocytes in a reliable and reproducible manner, to standardize the assessment of therapeutic efficacy. The ‘Concordance Atlas’ serves as a reference-standard for ongoing work to refine how ballooning is classified by both pathologists and AI.

MODERATOR DETAILS:

Mr. Anthony Lie
Head of Clinical Affairs, HistoIndex

HistoIndex

HistoIndex® is a Singapore-based leading MedTech company that specializes in its proprietary integrated stain-free AI digital pathology (AI-DP) platform, incorporating Second Harmonic Generation (SHG). The platform accurately quantifies post-treatment changes in disease features, particularly those that are unnoticeable with conventional microscopy and yet critical for the evaluation of therapeutic efficacy. HistoIndex’s technology is currently involved in multiple FDA clinical trials for Nonalcoholic Steatohepatitis (NASH) and Hepatitis B and has benefitted more than 150 organizations globally.

The meeting is free to attend

Register For Free