Targeting NASH by Integritas Communications

JOIN US FOR AN INTERACTIVE EVIDENCE-BASED BEST PRACTICESâ&#x201E;¢ CME DINNER SYMPOSIUM

MARQUIS BALLROOM, SALON 6-10 (MEETING LEVEL 2) Marriott Marquis Washington, DC

This activity is jointly provided by Global Education Group and Integritas Communications. This activity is supported by an educational grant from Allergan. This is not an official function/event of the American Association for the Study of Liver Diseases.

CME/MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

Zobair M. Younossi, MD, MPH, FAASLD CHAIR

FACULTY

Professor of Medicine, Virginia Commonwealth University-Inova Campus Chairman, Department of Medicine, Inova Fairfax Hospital Vice President for Research, Inova Health System Betty & Guy Beatty Center for Integrated Research Falls Church, Virginia, USA

Dr. Zobair Younossi is the Chairman, Department of Medicine, Inova Fairfax Medical Campus, and Vice President for Research of Inova Health System. He is also Professor of Medicine, Virginia Commonwealth University, Inova Campus, and Affiliate Professor of Biomedical Sciences at George Mason University, Fairfax, Virginia. Dr. Younossi earned his medical degree from the University of Rochester School of Medicine and Dentistry in Rochester, New York (Alpha Omega Alpha, 1989), and completed his residency in internal medicine as well as a fellowship in gastroenterology and hepatology at Scripps Clinic and Research Foundation in La Jolla, California. During his residency and fellowship, he earned his master of public health degree from San Diego State University (SDSU) School of Public Health in San Diego, California, being awarded both the Hanlon Award and Outstanding Student Award for SDSU. He then served as the Staff Hepatologist and Senior Researcher at the Cleveland Clinic Foundation, Cleveland, Ohio (1995-2000). In 2000, Dr. Younossi was recruited to establish Inova’s Center for Liver Diseases. The center is currently well known for its excellence in clinical hepatology, teaching, and research. Inova’s Center for Liver Diseases is not only involved in “cutting-edge” clinical trial protocols and outcomes research projects, but also has pioneered research in the genomics and proteomics of obesity and its related liver diseases. The center has participated in over 90 research projects in translational research, outcomes research, and “cutting-edge” clinical trials.

Vlad Ratziu, MD, PhD FACULTY

Professor of Hepatology Université Pierre et Marie Curie Hôpital Pitié-Salpêtrière Institute of Cardiometabolism and Nutrition Paris, France

Dr. Vlad Ratziu is professor of hepatology at the Université Pierre et Marie Curie and the Hôpital PitiéSalpêtrière Medical School in Paris, France. After completing his medical training at the Université Paris Descartes, he completed a 2-year postdoctoral fellowship at the Liver Center at the University of California in San Francisco, USA, and went on to earn a doctoral degree from Université Paris Diderot for his work on the pathophysiology of viral and metabolic liver fibrosis. Dr. Ratziu’s main research interests are in the field of nonalcoholic fatty liver disease (NAFLD); the mechanisms, risk factors, and progression of liver fibrosis in viral and metabolic diseases; and the treatment of viral hepatitis and hepatocellular carcinoma. He has participated in phase 1, 2, and 3 studies of nonalcoholic steatohepatitis and has published more than 230 papers in top-tier specialty journals. An associate editor for the Journal of Hepatology, Clinics and Research in Hepatology and Gastroenterology, he was also as a member of the editorial board of Hepatology. Dr. Ratziu coordinated the FLIP (Fatty Liver Inhibition of Progression) consortium, a program funded by the European 7th Framework Programme (FP7) to study the mechanisms of progression of liver disease in NAFLD in the largest European cohort of patients with NAFLD and to identify potential preventive and therapeutic strategies. Part of the Steering Committee of the Horizon 2020 NASH EPoS (Elucidating Pathways of Steatohepatitis) and the IMI2 (Innovative Medicines Initiative 2) LITMUS (Liver Investigation: Testing Marker Utility in Steatohepatitis) Consortia, he is also part of the organizing committee of the NASH – Therapeutic Agents (NASH-TAG) meetings (www.nash-tag.org).

Mary E. Rinella, MD FACULTY

Professor of Medicine Department of Gastroenterology and Hepatology Northwestern University Feinberg School of Medicine Chicago, Illinois, USA

Dr. Mary Rinella is a Professor of Medicine at Northwestern Universityâ&#x20AC;&#x2122;s Feinberg School of Medicine. She studied basic mechanisms of steatohepatitis with the support of the American Gastroenterological Association and the National Institutes of Health for 10 years. Currently her focus is on clinical research in the area of nonalcoholic fatty liver disease/NASH, both before and after liver transplantation. Her primary clinical focus within the NASH realm is on the associations between NASH and cardiovascular disease and the occurrence of NASH after liver transplantation. She is the Director of the Northwestern Fatty Liver Program and currently serves as Chair of the NAFLD/NASH special interest group at the American Association for the Study of Liver Diseases. Dr. Rinella received her medical degree from the University of Illinois, Chicago, fulfilled her residency at the University of Chicago Hospitals, and completed her fellowship at Northwestern University McGaw Medical Center.

TARGET AUDIENCE

The educational design of this activity addresses the needs of gastroenterologists, hepatologists, and other health care professionals involved in the diagnosis and treatment of nonalcoholic steatohepatitis (NASH).

EDUCATIONAL OBJECTIVES

After completing this activity, the participant should be better able to: • Use current epidemiologic and demographic data to enhance NASH identification

PREAMBLE

• Describe new insights into the pathophysiology of nonalcoholic fatty liver disease (NAFLD)/NASH progression that inform the development of emerging NASH therapies and biomarkers • Selectively employ liver biopsy and complementary noninvasive modalities for NAFLD/NASH diagnosis, staging, and monitoring • Discuss the emerging NASH therapies, including the combined use of agents with complementary mechanisms of action • Monitor patients over time for NASH progression and hepatocellular carcinoma, including proactive identification of appropriate patients for enrollment in clinical trials

AGENDA 7:00 pm – 7:05 pm

Welcome and Preactivity Assessment Zobair M. Younossi, MD, MPH, FAASLD

7:05 pm – 7:30 pm

Enhanced Understanding of the Progression From NAFLD to NASH and Beyond (Audience Q&A) Zobair M. Younossi, MD, MPH, FAASLD

7:30 pm – 8:00 pm

The Challenges of Diagnosing NASH (Audience Q&A) Mary E. Rinella, MD

8:00 pm – 8:35 pm

Emerging NASH Therapeutics (Audience Q&A) Vlad Ratziu, MD, PhD

8:35 pm – 8:45 pm

Case Presentation & Panel Discussion: Approaches to Management and Long-Term Monitoring of Patients With NASH for Fibrosis Progression and Hepatocellular Carcinoma (HCC)

8:45 pm – 8:50 pm

Postactivity Assessment

8:50 pm – 9:00 pm

Concluding Comments and Audience Q&A

REFERENCES

1. Haas JT, et al. Pathophysiology and mechanisms of nonalcoholic fatty liver disease. Annu Rev Physiol. 2016;78:181-205. 2. Hassan K, et al. Nonalcoholic fatty liver disease: a comprehensive review of a growing epidemic. World J Gastroenterol. 2014;20(34):12082-12101. 3. Estes C, et al. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2017 Aug 12 [Epub ahead of print]. 4. Calzadilla Bertot L, Adams LA. The natural course of non-alcoholic fatty liver disease. Int J Mol Sci. 2016;17(5):774. 5. Renelus B, Foster T. Noninvasive evaluation of nonalcoholic fatty liver disease. Clin Liver Dis. 2016;7(3):45-47. 6. Banini BA, Sanyal AJ. Current and future pharmacologic treatment of nonalcoholic steatohepatitis. Curr Opin Gastroenterol. 2017;33(3):134-141. 7. Bedossa P. Pathology of non-alcoholic fatty liver disease. Liver Int. 2017;37(suppl 1):85-89.

PHYSICIAN ACCREDITATION STATEMENT

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Global Education Group (Global) and Integritas Communications. Global is accredited by the ACCME to provide continuing medical education for physicians. This CME/CE activity complies with all requirements of the federal Physician Payment Sunshine Act. If a reportable event is associated with this activity, the accredited provider managing the program will provide the appropriate physician data to the Open Payments database.

PREAMBLE

STATEMENT of NEED/PROGRAM OVERVIEW

Nonalcoholic fatty liver disease (NAFLD) is a potentially progressive spectrum of liver disorders that includes among its more severe forms nonalcoholic steatohepatitis (NASH).1 Closely associated with rising rates of obesity and metabolic syndrome, the prevalence of NAFLD and NASH continues to trend upward, suggesting that over the next decade, patients, clinicians, and health care systems will face an exponential increase in burdens associated with this underrecognized epidemic.2-4 In addition to having a strong foundation in current best practices for NAFLD/NASH management, liver specialists must be prepared to appropriately integrate newer noninvasive diagnostic modalities into patient workups and have a good understanding of the mechanisms of action, latest efficacy and safety data, and potential prescribing considerations for the numerous NASH therapies currently in late-stage development.5,6 During this Evidence-Based Best Practices™ program, expert faculty will use animated illustrations to highlight clinically relevant pathways in the complex pathophysiologic mechanisms of NAFLD and NASH; discuss current recommendations on the use of liver biopsy and complementary, noninvasive modalities for NASH diagnosis and staging; interpret the latest evidence for emerging NASH treatments; and share their preferred risk-stratification strategies to predict prognoses, shape management decisions, and monitor disease progression.4-7

PHYSICIAN CREDIT DESIGNATION

Global Education Group designates this live activity for a maximum of 2.0 AMA PRA Category 1 Creditsâ&#x201E;˘. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

GLOBAL CONTACT INFORMATION

For information about the accreditation of this program, please contact Global at 303-395-1782 or cme@globaleducationgroup.com.

PREAMBLE

INSTRUCTIONS TO RECEIVE CREDIT

In order to receive credit for this activity, the participant must complete the program evaluation. A certificate will be emailed to the address provided on the evaluation form within 4 weeks.

FEE INFORMATION & REFUND/CANCELLATION POLICY

There is no fee for this educational activity.

DISCLOSURE of CONFLICTS of INTEREST

Global Education Group (Global) requires instructors, planners, managers, and other individuals and their spouses/life partners who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted by Global for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations. The faculty reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity: Zobair M. Younossi, MD, MPH, FAASLD

Consultant/Independent Contractor: Allergan plc; Bristol-Myers Squibb Company; Gilead Sciences, Inc.; Intercept Pharmaceuticals, Inc. Advisory Board: Janssen Pharmaceuticals, Inc.; Vertex Pharmaceuticals Incorporated

Vlad Ratziu, MD, PhD

Consultant: Alexion Pharma GmbH, Allergan plc, Boehringer Ingelheim International GmbH, Enterome Bioscience, Galmed Pharmaceuticals Ltd., GENFIT SA, Intercept Pharmaceuticals, Inc., Novartis AG, Pfizer Inc. Steering Committee: Allergan plc, Boehringer Ingelheim International GmbH, Galmed Pharmaceuticals Ltd., GENFIT SA, Intercept Pharmaceuticals, Inc.

Mary E. Rinella, MD

Consultant/Independent Contractor: Enanta Pharmaceuticals, Inc.; Gilead Sciences, Inc.; Immuron Ltd; Intercept Pharmaceuticals Inc.; Novartis Pharmaceuticals Corporation Grant/Research Support: NuSirt Biopharma, Inc.

Lindsay Borvansky

Nothing to disclose

Andrea Funk

Nothing to disclose

Ashley Marostica, RN, MSN

Nothing to disclose

Jim Kappler, PhD

Nothing to disclose

Jeanette Ruby, MD

Nothing to disclose

PREAMBLE

The planners and managers reported the following financial relationships or relationships to products or devices they or their spouses/life partners have with commercial interests related to the content of this CME activity:

DISCLOSURE OF UNLABELED USE

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the US Food and Drug Administration. Global Education Group (Global) and Integritas Communications do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

DISCLAIMER

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed in this activity should not be used by clinicians without evaluation of patient conditions and possible contraindications on dangers in use, review of any applicable manufacturerâ&#x20AC;&#x2122;s product information, and comparison with recommendations of other authorities.

SLIDES

CLINICAL PRACTICE GUIDELINES The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Chalasani N, et al. Hepatology. 2017 July 17. [Epub ahead of print] »» http://onlinelibrary.wiley.com/doi/10.1002/hep.29367/epdf

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO). J Hepatol. 2016;64(6):1388-1402. »» http://www.journal-of-hepatology.eu/article/S0168-8278(15)00734-5/pdf

CLINICAL RESOURCES Histological Scoring System for Nonalcoholic Fatty Liver Disease. Transplant Pathology Internet Services, 2009. »» http://tpis.upmc.com/changebody.cfm?url=/tpis/schema/NAFLD2006.jsp

MELD Score (Model for End-Stage Liver Disease) (12 and older). MD+CALC online calculator, 2016. »» https://www.mdcalc.com/meld-score-model-end-stage-liver-disease-12-older

NAFLD (Non-Alcoholic Fatty Liver Disease) Fibrosis Score.

RESOURCE CENTER

MD+CALC online calculator, 2016. »» https://www.mdcalc.com/nafld-non-alcoholic-fatty-liver-disease-fibrosis-score

PATIENT RESOURCES American College of Gastroenterology (ACG) Patient Education and Resource Center. The ACG website. provides a basic overview of NAFLD and includes patientcentered podcasts. »» http://patients.gi.org/topics/fatty-liver-disease-nafld/

American Liver Foundation. The American Liver Foundation website offers broad-based information and links to additional educational resources and support services for patients living with liver disease. »» http://www.liverfoundation.org/

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Health Information Center. The NIDDK website for NAFLD and NASH provides comprehensive patient-centered information and resources, including an overview of clinical-trial participation. »» https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash

SUGGESTED READING NAFLD: a multisystem disease. Byrne CD, Targher G. J Hepatol. 2015;62(suppl 1):S47-S64.

RESOURCE CENTER

»» http://www.journal-of-hepatology.eu/article/S0168-8278(14)00933-7/fulltext

A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. Friedman SL, et al. Hepatology. 2017 Aug 17. [Epub ahead of print]. »» http://onlinelibrary.wiley.com/doi/10.1002/hep.29477/pdf

Noninvasive imaging methods to determine severity of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hannah WN Jr, Harrison SA. Hepatology. 2016;64(6):2234-2243. »» https://www.ncbi.nlm.nih.gov/pubmed/27338123

Elevated serum ferritin is an independent predictor of histologic severity and advanced fibrosis among patients with nonalcoholic fatty liver disease. Kowdley KV, et al. Hepatology. 2012;55(1):77-85. »» https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245347/pdf/nihms326891.pdf

The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: a randomized, phase 2 trial. Loomba R, et al. Hepatology. 2017 Sep 11. [Epub ahead of print]. »» http://onlinelibrary.wiley.com/doi/10.1002/hep.29514/epdf

Characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis. Mohamad B, et al. Hepatol Int. 2016;10(4):632-639. »» https://www.ncbi.nlm.nih.gov/pubmed/26558795

Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Neuschwander-Tetri BA, et al. Lancet. 2015;385(9972):956-965. »» https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447192/pdf/nihms672595.pdf

Elafibranor, an agonist of the peroxisome proliferator-activated receptor-α and -δ, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening. Ratziu V, et al. Gastroenterology. 2016;150(5):1147-1159. »» http://www.gastrojournal.org/article/S0016-5085(16)00140-2/pdf

Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial.

RESOURCE CENTER

Ratziu V, et a. Hepatology. 2010;51(2):445-453. »» http://onlinelibrary.wiley.com/doi/10.1002/hep.23270/epdf

Management of NAFLD: a stage-based approach. Rinella ME, Sanyal AJ. Nat Rev Gastroenterol Hepatol. 2016;13(4):196-205. »» https://www.ncbi.nlm.nih.gov/pubmed/26907882

Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Targher G, et al. Diabetes. 2005;54(12):3541-3546. »» http://diabetes.diabetesjournals.org/content/54/12/3541

Extrahepatic manifestations of nonalcoholic fatty liver disease. VanWagner LB, Rinella ME. Curr Hepatol Rep. 2016;15(2):75- 85. »» https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874648/pdf/nihms-773290.pdf

Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Wong RJ, et al. Gastroenterology. 2015;148(3):547-555. »» http://www.gastrojournal.org/article/S0016-5085(14)01474-7/pdf

Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Younossi ZM, et al. Hepatology. 2016;64(1):73-84. »» http://onlinelibrary.wiley.com/doi/10.1002/hep.28431/full

Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality. Younossi ZM, et al. Hepatology. 2011;53(6):1874-1882.

RESOURCE CENTER

»» http://onlinelibrary.wiley.com/doi/10.1002/hep.24268/epdf

Please visit the CLINICAL RESOURCE CENTER for additional information and resources

www.ExchangeCME.com/NASHRESOURCES17

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