Global NASH Council

Zobair Younossi presents the first of 3 orals this afternoon at the American Diabetes Association conference. *NOTE: this is apparently the first time in 84 years that one person at the ADA conference presented 3 orals in a row! • NAFLD is characterized by hepatic steatosis without significant alcohol intake or other causes of CLD NAFLD is the most common chronic liver disease globally affecting 38% of world population. * Strongly associated with obesity, type 2 diabetes (T2D), and metabolic syndrome. * NASH is the progressive form of NAFLD leading to cirrhosis, liver failure, and hepatocellular carcinoma (HCC). * NAFLD term does not highlight the underlyning pathogenic pathway and may be stigmatizing Primary Objective: • Compare the clinical profiles and mortality outcomes of patients with NAFLD with those redefined under MASLD criteria using population-based data. Data Sources: • National Health and Nutrition Examination Survey III (NHANES III) with the linked Mortality file (through 2019). Significance: • Determine if the shift to the new nomenclature (MASLD) impacts clinical understanding and patient management. * NAFLD and MASLD definitions have very high concordance * About 5% of NAFLD don't meet criteria for MASLD * These patients are younger with less clinically overt metabolic dysfunction * No significant differences in long-term mortality between the two groups. * In general, the data generated under NAFLD definition, can be used for MASLD * To include NAFLD group who do not meet MASLD definition, the term early MASLD has been suggested and should be considered American Association for the Study of Liver Diseases (AASLD) EASL | The Home of Hepatology Global NASH Council Canadian Association for the Study of the Liver European Liver Patients' Association - ELPA James Kim

Oral presentation 3 by Zobair Younossi today “The Impact of Type 2 Diabetes on the Outcomes of Liver Transplantation in the United States: The data from the national registry 2007-2022” • There is a significant burden of type 2 diabetes among liver transplant candidates in the United States. • Overall, post-transplant survival of patients with pre-transplant is good • The presence of pre-transplant diabetes is independently associated with an increased risk of post-transplant mortality in liver transplant recipients. • The increased risk was greater in transplant patients without HCC but also significant in the HCC group, similar across CLD etiologies. • Optimal management of 2D before and after LT is critical Global NASH Council American Association for the Study of Liver Diseases (AASLD) American Diabetes Association EASL | The Home of Hepatology Canadian Association for the Study of the Liver Barcelona Institute for Global Health (ISGlobal)

Dr. Kenneth Cusi shares insights about the new MASLD/MASH Nomenclature. Why a Need for Increased Awareness about MASLD? * MASLD affects two out of three people with type 2 diabetes. * It increases the risk of developing cirrhosis, liver cancer and overall liver-related mortality. * Increases the risk of developing type 2 diabetes, cardiovascular disease and extrahepatic malignancies. * MASLD has a major negative impact on health-related quality of life and is a major economic burden. * MASLD is reversable with an early diagnosis and intervention Intervention encompasses a healthy lifestyle, some diabetes and obesity management pharmacotherapies, metabolic surgery and FDA-approved medications Positive Aspects of the New Nomenclature and Knowledge Gaps * The term "metabolic dysfunction" highlights the key role of insulin resistance and metabolic defects in the pathophysiology of MASLD.
Knowledge gap: To examine heterogeneity of insulin resistance and metabolic factors in people with MASLD * Prediabetes and diabetes are now clearly defined as cardiometabolic risk factors for MASLD.
Knowledge gap: - Better understand the role of prediabetes - Establish the role of different diabetes types (e.g., T1D) and novel endotypes EASL | The Home of Hepatology Global Liver Institute Global NASH Council European Liver Patients' Association - ELPA Mazen Noureddin, MD, MHSc Naim Alkhouri, MD, FAASLD Global NASH Council James Kim

‘Epidemiology of MASLD and Hepatology Perspective’ with Zobair Younossi MD, MPH “Prevalence rate of MASLD is now estimated to be 38%. In Pediatric if you ask me, it’s about 15%. In type 2 diabetes it is now about 69-70% in the most recent data.” Epidemiology of MASLD and Hepatology Perspective Summary * MASLD/MASH is the most common liver disease worldwide * The clinical (cirrhosis, liver cancer, liver death), humanistic (PROs) and economic burden of MASLD is growing * This liver disease is even more common in those with T2D
MASLD in the context of T2D and increasing components of MS is associated with higher rates of cirrhosis, HCC and liver death * Identification of these patients (especially from diabetes practices) and linking the to appropriate care for treatment of their liver disease is important Global NASH Council American Association for the Study of Liver Diseases (AASLD) EASL the home of Hepatology Jörn M. Schattenberg Jeffrey V. Lazarus Canadian Association for the Study of the Liver Canadian Association of Gastroenterology

Thank you Zobair Younossi for chairing this important collaborative multidisciplinary group of experts focused on MASLD/MASH. We can accomplish a lot working together globally. EASL | The Home of Hepatology Global NASH Council

We are now one big family. As members of the Global NASH Council, we are gathered together in Milan, Italy. Let's continue to work together, support each other, and drive progress in the field of liver health. Together, we can make a difference. Global NASH Council

It was a great morning hearing about all the updates from each committee and how much the Global NASH Council has accomplished. We are represented on the Patient Advisory Committee with Diane Langenbacher, PhD and Nikos Dedes co-chairing and now too on the Hepatology, Non-Hepatology Interface Committee, with Kenneth Cusi and M Paula Macedo co-chairing. Patient Advisory Committee members: Danjuma K. Adda, Henry Chang 张恩瑞, Wayne Eskridge, Helen Jordan, Achim Kautz, Yiannoula Koulla, Dee Lee, Vicki Mooney, Lorena Stoopen, Jeffrey V. Lazarus, Zobair Younossi Hepatology, Non-Hepatology Interface Committee members: Alice Kong, Amalia Gastaldelli, CYRIELLE CAUSSY, Diana Barb, Didac Mauricio, Fernando BRIL, Gerald Shulman, Giulio Marchesini, James Kim, Jay Shubrook, Michael Roden, Mustafa Kanat, Paul Brennan, Scott Isaacs, MD, FACP, FACE, Yusuf Yilmaz, Zobair Younossi

We are now one big family. As members of the Global NASH Council, we are gathered together in Milan, Italy. Let's continue to work together, support each other, and drive progress in the field of liver health. Together, we can make a difference. Global NASH Council