New targets for the treatment of NASH (NAFLD) in 2012?
|
|
- Loreen Ford
- 6 years ago
- Views:
Transcription
1 New targets for the treatment of NASH (NAFLD) in 2012? Dominique Larrey Service d Hépatogastroenterologie et transplantation Hôpital Saint Eloi CHU Montpellier INSERM 1040-IRB France Dom-larrey@chu-montpellier.fr
2 NASH Treatments Lifestyle - Nutrition - Physical exercice Drugs Bariatric surgery
3 Modify lifestyle?
4 Adapted physical activity?
5 Dr House advice?
6 Increase physical activity?
7 Change nutrition behavior?
8 NASH Regulation of nutrition and lifestyle - Reduction of steatosis by 20% within few days - Decrease/normalisation of transaminases - Improvement of glycaemia and lipidemia - Decrease of insulin-resistance - But. Long term maintenance is very difficult
9 Take care to avoid too difficult objectives
10 NASH Treatments Lifestyle - Nutrition - Physical exercice Drugs Bariatric surgery
11 Class of medications which have been evaluated on ALT, steatosis, inflammation and fibrosis Insulin sensitizing agents : glitazones, metformin Lipid lowering agents: statins, fibrates, gemfibrozil, PUVA omega 3 Drugs improving blood flow : pentoxifylline Anti-oxidants : UDCA, Vitamin E, betaine Weigth loss agents : cannabinoid modulators like CB1 antagonists : rimonabant
12 Thiazolidines-diones or glitazones anti-diabetics Agonists of PPARgs nuclear receptors Troglitazone withdrawn because hepatotoxicity. Rosiglitazone Pioglitazone
13 Glitazones Effects on transaminases Normalisation ALT/AST % transa. decrease Tetri 2003 Rosi 8 mg n=25 1 yr? 55% Ratziu 2008 Rosi 8 mg n=32 Placebo n=32 6 mon 38 % 7 % 30 % 10 % Promrat 2004 Pio 30 mg n=18 1 yr 72% 60% Sanyal 2004 Pio 30 mg+vit E n=10 vit E n=10 Belfort 2006 Pio 45 mg n=26 Placebo n=26 6 mon 6 mon 40 % 21 % 58 % 34 % Aithal 2008 Pio 30 mg n=37 Placebo n=37 1 yr 40 % 8 % After Ratziu 2009
14 Glitazones Histological results Steatosis Hépatocyte Inflammation Fibrosis Ballooning Tetri 2003 Rosi 50% of pts _ Ratziu 2008 Rosi Promrat 2004 Pio? Sanyal 2004 Pio -? - Belfort 2006 PIo - Arthal 2008 Pio - - After Ratziu 2009
15 Pioglitazone or vitamin E x 96 weeks in NASH TT (247nondiabetic pts) PIVENS TRIAL Primary objective : decrease by at least 2 points of NAS score Limit of significance : p < 0,025 with decrease by at least one point of hepatocyte ballooning without aggravation of fibrosis Only vitamin E reached primary objective 50 p < 0,001 p < 0,04 Proportion de patients (%) /84 NAT = 4,4 16/83 26/80 NAT = 6,6 0 Vit. E Placebo Ploglitazone NAT : number of patients to treat to obtain the primary criteria in a patient Sanyal AJ et al NEJM 2010;362:1675
16 Pioglitazone or vitamin E in NASH treament Vitamine E and pioglitazone improved lobular inflammation Vitamine E and pioglitazone improved hepatocyte ballooning 95 Proportion de patients (%) Aggravation Amélioration Vit. E p < 0,01 grade 0,6 grade 0,2 p < 0,001 grade 0,7 Placebo Ploglitazone Proportion de patients (%) Aggravation Amélioration grade 0,5 Vit. E p < 0,02 grade 0,2 Placebo p < 0,02 grade 0,4 Ploglitazone Proportion de patients (%) Vitamine E and pioglitazone did not improved fibrosis score Aggravation Amélioration grade 0,3 grade 0,1 Vit. E n.s. Placebo n.s. grade 0,4 Ploglitazone Sanyal et al. NEJM 2010;363:1675
17 PIVENS Study transaminase improvement Sanyal et al. N E J Med 2010; 362:1675
18 PIVENS Study insulin resistance improvement Sanyal et al. N E J Med 2010; 362:1675
19 Limitation of PIVENS study Missing follow-up biopsy: - 11 in placebo group - 4 in vitamin E group - 10 in pioglitazone group
20 Limitation of glitazone efficacy/tolerance ratio - Weight gain 4-5 kg within the first 6 months of treatment - Risk of cardiac decompensation with rosiglitazone - Risk of bladder carcinoma with pioglitazone - Bone loss and fractures in women
21 NASH treatment - Metformine Experimental background Controlled clinical trials - Uygun 2004 CS n=17 - Schwimmer 2005 CS n=10 - Bugiasini 2005 CS n=55 - Duseja 2007 CS n=7 - Nar 2008 CS n=34 - Idilman 2008 CS n=74 - Haukeland 2009 CS n=48 - Schields 2009 CS n=19 Decrease in transaminases Meta-analysis :No significant histological effects Musso et al Hepatology 2010; 52:79-104
22 Class of medications which have been evaluated on ALT, steatosis, inflammation and fibrosis Insulin sensitizing agents : glitazones, metformin Lipid lowering agents: statins, fibrates, gemfibrozil, PUVA omega 3 Drugs improving blood flow : pentoxifylline Anti-oxidants : UDCA, Vitamin E, betaine Weigth loss agents : cannabinoid modulators like CB1 antagonists : rimonabant
23 Effect of omega 3 PUFA on steatosis Meta-analysis Parker et al. J Hepatol 2012;56:944
24 Effect of omega 3 PUFA on ALT Meta-analysis Parker et al. J Hepatol 2012;56:944
25 Treatment by omega 3 PUFA Meta-analysis Parker et al. J Hepatol 2012;56:944 - Decrease of steatosis - Optimal dosage unknown but > 0,83 g/day - Requirement of well-designed controlled studies
26 Protecting effects of ursodesoxycholic acid (UDCA) in steatohepatitis Rodrigues, JCI 1998 Qiao, Hepatology 2002 Oxidative Stress TNF a Neuman, JGH 2002 Apoptosis UDCA Endotoxinemia Dysfunction NKT cells Nishigaki, DDS 1996 Necrosis Induced by Biliary acids Kobak, Gastro 2002 A Schwarzenberg, Pediatr Res 1996
27 UDCA controlled trials Dose (mg/kg) Duration (month) Biopsy Weight ALT Steatosis Inflam Fibrosis Lindor Pre-post = - - Dufour ± vit E 12 Pre-post = + + (UDCA + vit E) + (UDCA + vit E) - UrsoNash Pré = ++?? ± Ulrich Pré = -
28 Metabolic response at M12 UDCA % PLACEBO % p Glycaemia -2.2 [20] 3.8 [24] 0,002 Insuline -19 [39] 0 [60] 0,038 HOMA -20 [58] 6 [83] 0,009 Significant decrease of HbA1c (p<0,001) in UDCA group No effect on HDLc, triglycerides, cholesterol and LDLc % decrease compared to basal level, median [IQR]
29 NASH Pharmacological treatments New targets More than 25 drugs in Phase1 and 2 trials - Phosphodiesterase inhibitor PDE4 - Adipokine modulators ( adiponectin, leptin, resistin) - Inhibitors of pro-inflammatory cytokines - Modulators of cannabinoid receptors (rimonabant),other CR1B without central effects, CR2B - Cysteamine - Gliptines - PPAR alpha, PPAR delta agonists - Inhibitors of angiotensine I receptor ( sartans : telmisartan, valsartan, losartan) - Pro-biotics (intestin liver axis) (microbiome) - Agents suppressing fat in the liver
30 Phosphodiesterase PDE4 Concept Basis PDE are enzymes responsible for hydrolysis of cyclic nucleotides,including AMPc and GMPc PDE Inhibitors are able to decrease inflammatory response and to decrease the production of inflammation mediators, including cytokines such as TNF-alpha
31 Phosphodiesterase PDE4 Concept Basis PDE are enzymes responsible for hydrolysis of cyclic nucleotides,including AMPc and GMPc PDE Inhibitors are able to decrease inflammatory response and to decrease the production of inflammation mediators, including cytokines such as TNF-alpha Phase 2 studies provide no results vs placebo on ALT!!!
32 Anti-apoptotic agents Concept Basis Aptotosis leads to inflammation by activation of nuclear factor kappab and by inducing adhesion molecules,chemokines These apoptosis pathways are activated in NASH Hepatocyte apoptosis is increased in NASH GS-9450 is a caspase inhibitor against caspase 1,8,9 Caspase 8 is a key molecule for apoptosis induction
33 Effect of GS-9450 on apoptotis-mediated liver injury in NASH (phase 2 study) Design 124 patients With NASH ( biopsy) Randomized, double-blind trial GS-9450 QD 1,5,10,40 mg/day, 4 weeks vs placebo Results In the 40 mg group: CK-18 fragment decreased (NS) ALT decreased by 47 IU vs 2 IU in placebo group (P<0.0001)
34 Effect of GS-9450 on apoptotis-mediated liver injury in NASH (phase 2 study) Randomized, double-blind trial 124 pts with NASH Normalisation of ALT at week 4
35 Aramchol New synthetic lipidic molecule associating a mixture of cholic acid and saturated fatty acids susceptible to reduce hepatic fat. Aramchol partially inhibits SCD1 (Stearoyl-CoA desaturase 1), a regulator of lipid metabolism In rat, Fatty acid bile acid conjugates (FABAC) treatment prevented the occurrence steatosis in animals with high lipid diet (1). In mice, aramchol was shown to decrease adiposity and to increase energy stipend (2). 1.Gilat T et al. Prevention of diet-induced fatty liver in experimental animals by the oral administration of a fatty acid bile acid conjugate (FABAC). Hepatology. 2003;38: Gonen A et al. Fatty acid bile acid conjugates inhibit atherosclerosis in the C57BL/6 mouse model. Pathobiology ;70:215-8.
36 126 Effect of Aramchol in NASH Phase 2 randomised double-blind trial versus placebo 60 patients with NASH (biopsy) Aramchol : 300 mg versus 100 mg versus placebo for 3 months Evaluation of steatosis course by magnetic nuclear resonance spectroscopy 20 Evolution relative de la stéatose par SRMN (%) ,4 % p = 0,35 p = 0,02-2,9 % -12,6 % -20 Placebo (n = 20) Aramchol 100 mg/j (n = 20) Aramchol 300 mg/j (n = 20) Oren R, EASL 2012, Abs. 1418
37 Bariatric surgery Vertical-banded Gastroplasty Banding Gastric By-pass
38 Bariatric surgery and NASH success within the first year 890 severly obese patients with clinical, biological, histological evaluation before and one and et 5 years after bariatric surgery Course after one year after surgery in patients NASH (NAS > 5) Kg/m² % BMI * Avant chirurgie Steatosis Hepatic lesions Fibrosis * * * Avant chirurgie 1 an 1 an UI/ml ,5 0,5 As soon as 1 Yr after bariatric surgery liver lesions decrease 1 0 ALT * Avant chirurgie Avant chirurgie 1 an 1 an Inflammation Ballonisation 1/QUICKI Insuline-resistance ,5 1 0,5 0 Avant chirurgie Avant chirurgie * 1 an 1 an * p < 0, Lassailly G, EASL 2012, Abs. 6
39 Bariatric surgery and NASH success within the first year 125 Clinical, biological, histological evolution between one and 5 years after surgery in patients with NASH (NAS > 5) Kg/m² BMI p = 0,8 1 an 5 ans UI/ml ALT p = 0,9 1 an 5 ans 1/QUICKI Insuline-resistance 4 p = 0, an 5 ans % Steatosis Liver lesions Fibrosis p = 0,015 1 an 5 ans 0,8 0,6 0,4 0,2 0 Inflammation p = 0,9 p = 0,78 1 an 5 ans Ballonisation 2 1,5 1 0,5 0 p = 0,24 1 an 5 ans Beyond one year post surgery, there is no further improvement of fibrosis Lassailly G, EASL 2012, Abs. 6
40 NASH treatment Conclusion Pharmacological treatment necessary but: Therapeutic results still very limited Most tested drugs improve/normalise transaminases Effects on histological lesions much less documented: - decrease of steatosis : yes - decrease of inflammation : variable - decrease of fibrosis : unclear Many questions on indications, type, duration of TT and evaluation criteria -
41 Pharmacologic treatment of NASH Questions - What are the best targets? - What the adequate short mean - long term criteria evaluation (3-12 months? ) to assess efficacy/response ratio and strategy? - What is the adequate duration of treatment? Is there any possibility to stop it? - Interest of associated treatments (anti-ir, anti-oxidants, antiinflammatory agents, anti-fibrosing agents?) Who to treat? With which degree of lesions?
tage Percent Total & over Total & over Men Women Men Women
Paul Angulo, MD, FACG, AGAF Professor of Medicine, Section Chief of Hepatology Division i i of Digestive i Diseases and Nutrition i University of Kentucky Medical Center Lexington, KY Paul Angulo, MD University
More informationWHAT CAN YOU USE IN YOUR CLINIC TODAY FOR THE TREATMENT OF NASH?
WHAT CAN YOU USE IN YOUR CLINIC TODAY FOR THE TREATMENT OF NASH? Helena Cortez-Pinto Laboratório de Nutrição, FML, Serviço de Gastrenterologia, Hospital St Maria, Lisboa, Portugal EASL Governing Board:
More informationNAFLD: US GUIDELINES. US Guidelines for NAFLD
NAFLD: US GUIDELINES Arun J Sanyal M.D. Charles Caravati Professor of Medicine Virginia Commonwealth University School of Medicine US Guidelines for NAFLD Represents consensus amongst AGA, AASLD and ACG
More informationNONALCOHOLIC FATTY LIVER DISEASE
NONALCOHOLIC FATTY LIVER DISEASE Kiran Bambha, MD, MSc Hepatology and Liver Transplantation University of Colorado Denver April 13, 2012 Non-Alcoholic Fatty Liver Disease (NAFLD) Terminology Pathogenesis
More informationFatty liver disease: What do we know?
Fatty liver disease: What do we know? Prof. Dr. Claus Niederau Katholische Kliniken Oberhausen ggmbh St. Josef-Hospital Academic Teaching Hospital University of Duisburg-Essen NAFLD Non-Alcoholic Fatty
More informationTherapeutic targets and the management of NASH
Therapeutic targets and the management of NASH Joo Hyun Sohn, MD. Professor of Medicine, College of Medicine, Hanyang University Division of Gastroenterology and Hepatology Hanyang University Guri Hospital
More informationNONALCOHOLIC FATTY LIVER DISEASE. Non-Alcoholic Fatty Liver Disease (NAFLD) Primary NAFLD. April 13, 2012
NONALCOHOLIC FATTY LIVER DISEASE Kiran Bambha, MD University of Colorado Denver April 13, 2012 Non-Alcoholic Fatty Liver Disease (NAFLD) Primary NAFLD Simple Steatosis Fatty hepatocytes Intracellular fat
More informationNAFLD & NASH. Naga Chalasani, MD, FACG Professor of Medicine and Cellular & Integrative Physiology Director, Division of GI and Hepatology
NAFLD & NASH Naga Chalasani, MD, FACG Professor of Medicine and Cellular & Integrative Physiology Director, Division of GI and Hepatology Indiana University School of Medicine ACG Midwest Regional Course,
More informationNon-Alcoholic Fatty Liver Disease
Non-Alcoholic Fatty Liver Disease None Disclosures Arslan Kahloon M.D Chief, Division of Gastroenterology and Hepatology University of Tennessee College of Medicine Chattanooga Objectives Understand the
More informationNAFLD/NASH. Definitions. Pathology NASH. Vicki Shah PA-C, MMS Rush University Hepatology
NAFLD/NASH Vicki Shah PA-C, MMS Rush University Hepatology Definitions NAFLD Evidence of hepatic steatosis by histology (5%) or imaging No causes for secondary fat accumulation EtOH, Drugs, hereditary
More informationFatty Liver Disease. Mark Thursz. Imperial College
Fatty Liver Disease Mark Thursz Imperial College Non-Alcoholic Fatty Liver Disease UK adult obesity (BMI>30) 1980: 6% [M], 8% [F]. 1997: 17% [M], 20% [F]. By 2004, 23.6% of men and 23.8% of women were
More informationUpdate on Non-Alcoholic Fatty Liver Disease. Timothy R. Morgan, MD Chief, Hepatology, VA Long Beach Professor of Medicine, UCI
Update on Non-Alcoholic Fatty Liver Disease Timothy R. Morgan, MD Chief, Hepatology, VA Long Beach Professor of Medicine, UCI February 3, 2018 Disclosure Clinical trials: Genfit Speaker s Bureau: none
More informationNAFLD - therapeutic intervention. CP Day Institute of Cellular Medicine Newcastle University UK
NAFLD - therapeutic intervention CP Day Institute of Cellular Medicine Newcastle University UK Therapy for NAFLD Why worry about NAFLD? Management strategy - who to treat? Therapies directed at features
More informationNon-Alcoholic Steatohepatitis (NASH): What the Gastroenterologist Should Know
Non-Alcoholic Steatohepatitis (NASH): What the Gastroenterologist Should Know Naga P. Chalasani, MD, FACG Professor of Medicine and Cellular & Integrative Physiology Director, Division of GI and Hepatology
More informationMETABOLIC SYNDROME AND HCV: FROM HCV
METABOLIC SYNDROME AND HCV: FROM THEORY TO PRACTICE HCV Steatosis Insulin resistance Arun J Sanyal M.D. Chairman, Div. of Gastroenterology, Hepatology and Nutrition Virginia Commonwealth University Richmond,
More informationHow to manage patients with NASH? Dr Raluca Pais Institute of Cardiometabolisme and Nutrition (ICAN) Hôpital Pitie Salpetrière, Paris
How to manage patients with NASH? Dr Raluca Pais Institute of Cardiometabolisme and Nutrition (ICAN) Hôpital Pitie Salpetrière, Paris CLINICAL CASE 1996. 54 years old female Department of Primary CV Prevention
More informationPEDIATRIC FOIE GRAS: NON-ALCOHOLIC FATTY LIVER DISEASE
PEDIATRIC FOIE GRAS: NON-ALCOHOLIC FATTY LIVER DISEASE Updates on New insights into NAFLD and NASH pathophysiology New AASLD/AGA/ACG guidelines for NAFLD and NASH, as pertains to pediatrics Evidence-based
More informationNonalcoholic Fatty Liver Disease in Children: Typical and Atypical
Nonalcoholic Fatty Liver Disease in Children: Typical and Atypical Disclosure Naim Alkhouri, MD discloses the following relationships with commercial companies: Membership in the Speakers Bureau for Alexion
More informationNAFLD: ACG Southern Regional Course Nashville, TN. Speaking - None
NAFLD: 2015 Naga Chalasani, MD, FACG David W. Crabb Professor of Medicine Director, Division of GI and Hepatology Indiana University School of Medicine ACG Southern Regional Course Nashville, TN Disclosures
More informationNAFLD: evidence-based management. Curso de residentes AEEH Salvador Augustin, MD Liver Unit Vall d Hebron Hospital Barcelona, Spain
NAFLD: evidence-based management Curso de residentes AEEH 2017 Salvador Augustin, MD Liver Unit Vall d Hebron Hospital Barcelona, Spain Clinical case - 55 yo female - Sent for incidental steatosis at abdominal
More informationInternal Medicine Grand Rounds University of Texas Southwestern Medical Center October 5, 2018
Internal Medicine Grand Rounds University of Texas Southwestern Medical Center October 5, 2018 Nonalcoholic Fatty Liver Disease (NAFLD) Turns 38-What Have We Learned? Jay D. Horton, M.D. This is to acknowledge
More informationDietary supplementation in treating non-alcoholic fatty liver disease Dr. Ahmad Saedi Associate Professor School of Nutritional Sciences and
Dietary supplementation in treating non-alcoholic fatty liver disease Dr. Ahmad Saedi Associate Professor School of Nutritional Sciences and Dietetics Tehran University of Medical Sciences Honorary Academic
More informationNON-ALCOHOLIC FATTY LIVER DISEASE:
NON-ALCOHOLIC FATTY LIVER DISEASE: ROLE OF THE PRIMARY PROVIDER Archita P. Desai, MD Assistant Professor of Medicine University of Arizona 25 th Annual Southwestern Conference on Medicine Outline Pathophysiology
More informationWhat to do about the high ALT picked up at the annual review. Dr Michael Yee Consultant in Diabetes and Endocrinology
What to do about the high ALT picked up at the annual review Dr Michael Yee Consultant in Diabetes and Endocrinology Mrs DC HPC PMH Type 2 Diabetes (decades) Regular retinal screening No foot complications/neuropathy
More informationThe Skinny On Non Alcoholic Fatty Liver Disease
The Skinny On Non Alcoholic Fatty Liver Disease UCSF Advances in Internal Medicine Monika Sarkar, MD, MAS UCSF Division of GI/Hepatology June 24th, 2015 Non Alcoholic Fatty Liver Disease: Outline Pathogenesis
More informationNASH: WHAT YOU NEED TO KNOW
NASH: WHAT YOU NEED TO KNOW MARCELO KUGELMAS, MD, FACP SOUTH DENVER GASTROENTEROLOGY CENTER FOR DISEASES OF THE LIVER AND PANCREAS, SWEDISH MEDICAL CENTER CLINICAL ASSOCIATE PROFESSOR OF MEDICINE, UNIVERSITY
More informationNon-alcoholic fatty liver disease: time to take note and manage. Philip Newsome Professor of Hepatology & Director of Centre for Liver Research
Non-alcoholic fatty liver disease: time to take note and manage Philip Newsome Professor of Hepatology & Director of Centre for Liver Research Disclosures Consultancy, Co-ordinating Investigator roles
More informationPREVALENCE OF NAFLD & NASH
- - PREVALENCE OF & USA Prevalence in Middle Age Patients San Antonio, Texas (Williams et al., Gastroenterology 2011; 140:124-31) Dallas Heart Study Prevalence Numbers (Browning et al., Hepatology 2004;40:1387-95)
More informationImproving Access to Quality Medical Care Webinar Series
Improving Access to Quality Medical Care Webinar Series Presented by The Arizona Telemedicine Program and the Southwest Telehealth Resource Center 2015 UA Board of Regents Welcome AZ, UT, CO, NM & NV FLEX
More informationUpdate on Nonalcoholic Fatty Liver Disease. Kathleen E Corey, MD, MPH, MMSc Director, Mass General Fatty Liver Clinic
Update on Nonalcoholic Fatty Liver Disease Kathleen E Corey, MD, MPH, MMSc Director, Mass General Fatty Liver Clinic Outline Defining the phenotypes of nonalcoholic fatty liver disease NAFLD Diagnostics
More informationNAFLD & NASH: Russian perspective
NAFLD & NASH: Russian perspective Vasily Isakov, MD, PhD Professor, Chief, Department Gastroenterology & Hepatology, Federal Research Center of nutrition, biotechnology and food safety Disclosures Received
More informationInvestigating general liver disease/transaminitis
BHIVA Autumn Conference London 14 October 2016 Investigating general liver disease/transaminitis Emmanuel A. Tsochatzis Senior Clinical Lecturer and Consultant Hepatologist Institute for Liver and Digestive
More informationMeta-Analysis of Randomized Controlled Trials of Pharmacologic Agents in Non-alcoholic Steatohepatitis
538 Said A, et al., 2017; 16 (4): 538-547 ORIGINAL ARTICLE July-August, Vol. 16 No. 4, 2017: 538-547 The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for Study
More informationReview Article A Comprehensive Updated Review of Pharmaceutical and Nonpharmaceutical Treatment for NAFLD
Gastroenterology Research and Practice Volume 2016, Article ID 7109270, 17 pages http://dx.doi.org/10.1155/2016/7109270 Review Article A Comprehensive Updated Review of Pharmaceutical and Nonpharmaceutical
More informationWHAT THE EXPERIMENTAL MODELS CAN TEACH US IN NAFLD/NASH? Claudio Tiribelli, MD PhD Scientific Director FIF
WHAT THE EXPERIMENTAL MODELS CAN TEACH US IN NAFLD/NASH? Claudio Tiribelli, MD PhD Scientific Director FIF ctliver@fegato.it Worldwide estimated prevalence of NAFLD distribution of PNPLA3 genotypes 2017-Younussi
More informationEarly life determinants of Non-Alcoholic Fatty Liver Disease and NASH DR JULIANA MUIVA-GITOBU KENYA PAEDIATRIC ASSOCIATION CONFERENCE APRIL 2016.
Early life determinants of Non-Alcoholic Fatty Liver Disease and NASH DR JULIANA MUIVA-GITOBU KENYA PAEDIATRIC ASSOCIATION CONFERENCE APRIL 2016. Outline Definition NAFLD and NASH Magnitude of the problem
More informationDiseases to Watch. Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic
Diseases to Watch Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic steatohepatitis (NASH) - Prevalence and Symptoms - Risk Factors and Potential treatments - Target identification for NASH Robert
More informationEASL-EASD-EASO Clinical Practice Guidelines for the management and treatment of NAFLD. Francesco Negro University of Geneva - Switzerland
EASL-EASD-EASO Clinical Practice Guidelines for the management and treatment of NAFLD Francesco Negro University of Geneva - Switzerland EASL EASD - EASO G Marchesini CP Day J-F Dufour A Canbay V Nobili
More informationFATTY LIVER DISEASE (NAFLD) (NASH) A GROWING
NON ALCOHOLIC FATTY LIVER DISEASE () & NON ALCOHOLIC S T E ATO H E PAT I T I S () ADDRESSING A GROWING SILENT EPIDEMIC Prevalence of & USA Prevalence in Middle Age Patients San Antonio, Texas (Williams
More informationWhat is NAFLD?.NASH? Presenter Disclosure Information. Learning Objectives. Case 1: Rob. Questions Pertinent to Rob
Presenter Disclosure Information 5 6pm Nonalcoholic Fatty Liver Disease (NAFLD): Another Obesity-Related Epidemic SPEAKER Elliot Tapper, MD The following relationships exist related to this presentation:
More informationFollow-up of pediatric chronic liver disease
IV CONVEGNO ITALO-BRASILIANO DI PEDIATRIA E NEONATOLOGIA SALVADOR DE BAHIA 21-23 MARZO 2006 Follow-up of pediatric chronic liver disease Antonio Colecchia, Luca Laudizi Dpt of Internal Medicine and Gastroenterology
More informationNON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) NON-ALCOHOLIC STEATOHEPATITIS (NASH) ADDRESSING A GROWING SILENT EPIDEMIC
NON-ALCOHOLIC FATTY LIVER DISEASE () & NON-ALCOHOLIC STEATOHEPATITIS () ADDRESSING A GROWING SILENT EPIDEMIC PREVALENCE OF / USA Prevalence in Middle Age Patients San Antonio, Texas (Williams et al., Gastroenterology
More informationFatty Liver, NASH: new diagnostics and new treatments
Fatty Liver, NASH: new diagnostics and new treatments Robert G Gish MD Professor Consultant Stanford University HASLD TP HCMC June 2016 NAFLD: the hepatic manifestation of the metabolic syndrome Obesity
More informationNAFLD/NASH in Sub- Saharan Africa
NAFLD/NASH in Sub- Saharan Africa Corné Kruger Gastroenterologist Durbanville Mediclinic Cape Town Liver Interest group meeting: Cape Town 2015 Introduction NAFLD is the most common liver disease disease
More informationYun-Jung Choi, Jiangao Song, Jeff D. Johnson, Charles McWherter. NASH-TAG Conference Park City, Utah January 4, 2019
Combination Therapy of Seladelpar and Liraglutide Attenuates Obesity, Hepatic Steatosis and Fibrosis in a Diet-induced and Biopsy-confirmed Mouse Model of NASH Yun-Jung Choi, Jiangao Song, Jeff D. Johnson,
More informationNASH : Diagnosis and investigation. VII Workshop international, Curitiba, Brazil 29/08/2014
NASH : Diagnosis and investigation VII Workshop international, Curitiba, Brazil 29/08/2014 Vlad Ratziu, Université Pierre et Marie Curie, Hôpital Pitié Salpêtrière, Paris, France Usual diagnostic circumstances
More informationNON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) NON-ALCOHOLIC STEATOHEPATITIS (NASH) ADDRESSING A GROWING SILENT EPIDEMIC
NON-ALCOHOLIC FATTY LIVER DISEASE () & NON-ALCOHOLIC STEATOHEPATITIS () ADDRESSING A GROWING SILENT EPIDEMIC PREVALENCE OF / USA Prevalence in Middle Age Patients San Antonio, Texas (Williams et al., Gastroenterology
More informationNon alcoholic fatty liver and Non alcoholic Steatohepatitis. By Dr. Seham Seif
Non alcoholic fatty liver and Non alcoholic Steatohepatitis By Dr. Seham Seif Definition NAFL describe a common clinicopathological conditions characterized by significant lipid deposition in the hepatocytes
More informationModern view of non-alcoholic fatty liver disease Key words:
Modern view of non-alcoholic fatty liver disease T. O. Tanryberdieva, M. C. Beknepesova, V. A. Gurbanov, O. N. Agahanowa Turkmenistan State Medical University, Ashkhabad, Turkmenistan Key words: non-alcoholic
More informationFatty Liver Disease A growing epidemic
Fatty Liver Disease A growing epidemic Updates in GIM for Primary Care Don C. Rockey March 9 th, 2018 Disclosures 2018 Research Funding (all to MUSC) NIH/NIDDK Actelion Pharmaceuticals Gilead Sciences
More information[Sem Liver Disease 21(1):81-88, Thieme Medical Publishers, Inc.]
Treatment of Nonalcoholic Fatty Liver: Present and Emerging Therapies [Sem Liver Disease 21(1):81-88, 2001. 2001 Thieme Medical Publishers, Inc.] Paul Angulo, M.D., and Keith D. Lindor, M.D., Division
More informationUpdate on Clinical Management
Non-Alcoholic Fatty Liver Disease Update on Clinical Management Lisa J. Yoo, D.O. Gastroenterologist Regional Gastroenterology INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is characterized by
More informationImproving the Lives of Patients with Liver Diseases
Improving the Lives of Patients with Liver Diseases Corporate Presentation March 2019 Safe Harbor Statement This presentation contains "forward-looking" statements that involve risks, uncertainties and
More informationDisclosures. The Typical Therapeutic Pyramid $$$ The NAFLD Umbrella. The Big Question: What are the treatment options for NASH?
Disclosures I have the following relationships to disclose: Ethicon Endo Surgery Inc. Galectin Therapeutics Synageva Biopharma Raptor Pharmaceuticals I will be discussing off label use of medications in
More informationManagement of autoimmune hepatitis. Pierre-Emmanuel RAUTOU Inserm U970, Paris Service d hépatologie, Hôpital Beaujon, Clichy, France
Management of autoimmune hepatitis Pierre-Emmanuel RAUTOU Inserm U970, PARCC@HEGP, Paris Service d hépatologie, Hôpital Beaujon, Clichy, France Case 1 52 year-old woman, referred for liver blood tests
More informationIL METABOLISMO EPATICO DEI CARBOIDRATI IN FISIOLOGIA E PATOLOGIA
UNIGASTRO Il fegato come centrale metabolica e i fattori di danno oltre ai virus epatitici IL METABOLISMO EPATICO DEI CARBOIDRATI IN FISIOLOGIA E PATOLOGIA Dr Elisabetta Bugianesi Divisione di Gastro-Epatologia
More informationPrognosis of NASH VII Workshop Intenracional de Actualizaçao em Hepatologia, Aug 29th 2014
Prognosis of NASH VII Workshop Intenracional de Actualizaçao em Hepatologia, Aug 29th 2014 Vlad Ratziu, Université Pierre et Marie Curie, Hôpital Pitié Salpêtrière, Paris, France NASH : a severe hepatic
More informationFatty Liver in HIV. Richard K. Sterling, MD, MSc, FACP, FACG
Fatty Liver in HIV Richard K. Sterling, MD, MSc, FACP, FACG Professor of Medicine Chief, Section of Hepatology Director, HIV-Liver Disease Virginia Commonwealth University Liver-Related Deaths in HIV 1246
More informationEASL EASD EASO Clinical practice guidelines for the management of nonalcoholic fatty liver disease.
Commentary. EASL EASD EASO Clinical practice guidelines for the management of nonalcoholic fatty liver disease. Christopher D. Byrne 1,2, Giovanni Targher 3 1 Nutrition and Metabolism, Faculty of Medicine,
More informationNon-Alcoholic Fatty Liver Diseasean underestimated epidemic
Non-Alcoholic Fatty Liver Diseasean underestimated epidemic Amir Shlomai MD,PhD Head, Department of Medicine D The Liver Institute Rabin Medical Center, Beilinson Hospital The IASLD semi-annual meeting-
More informationObesity, Inflammation and Liver Cancer
Obesity, Inflammation and Liver Cancer Richard Moreau, M.D., 1 INSERM U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, 2 Université Denis Diderot Paris 7, 3 Service d Hépatologie, Hôpital Beaujon,
More informationBiopsies. macrovesicular steatosis (zone III) Criteria for Dx of NASH. Liver Ultrasound Report. Definition of NASH
Definition of NASH Nonalcoholic steatohepatitis (NASH) is the term used to describe the distinct clinical entity in which patients lack a history of significant alcohol consumption but have liver biopsy
More informationStudy Design to Validate Biomarkers of Therapeutic Response in Pre-cirrhotic NASH
Study Design to Validate Biomarkers of Therapeutic Response in Pre-cirrhotic NASH Brent A. Neuschwander-Tetri, MD, FAASLD Professor of Internal Medicine Director, Division of Gastroenterology and Hepatology
More informationDisclosure. Objectives. Smash the Nash: A practical approach to fatty liver disease
Smash the Nash: A practical approach to fatty liver disease Bruce D. Askey, MS, ANP-BC Associate Lecturer North Andover, MA Adult Nurse Practitioner Dept. of Hepatology/Gastroenterology Guthrie Clinic
More informationAn Update on the Pharmacological Treatment of Nonalcoholic Fatty Liver Disease: Beyond Lifestyle Modifications
REVIEW An Update on the Pharmacological Treatment of Nonalcoholic Fatty Liver Disease: Beyond Lifestyle Modifications Naim Alkhouri, M.D.,*, and Andrea Scott, B.S.* Nonalcoholic fatty liver disease (NAFLD)
More informationNonalcoholic Steatohepatitis National Digestive Diseases Information Clearinghouse
Nonalcoholic Steatohepatitis National Digestive Diseases Information Clearinghouse National Institute of Diabetes and Digestive and Kidney Diseases NATIONAL INSTITUTES OF HEALTH Nonalcoholic steatohepatitis
More informationABNORMAL LIVER FUNCTION TESTS. Dr Uthayanan Chelvaratnam Hepatology Consultant North Bristol NHS Trust
ABNORMAL LIVER FUNCTION TESTS Dr Uthayanan Chelvaratnam Hepatology Consultant North Bristol NHS Trust INTRODUCTION Liver function tests Cases Non invasive fibrosis measurement Questions UK MORTALITY RATE
More informationPBC features and management in the era of UDCA and Budesonide
PBC features and management in the era of UDCA and Budesonide Raoul Poupon, MD Université P&M Curie, AP-Hôpitaux de Paris, Inserm, Paris, France The changing pattern of PBC Over the last 2 decades: More
More informationWORKSHOP. How to manage patients with NASH? Pr Jérôme Boursier Angers, France
WORKSHOP How to manage patients with NASH? Pr Jérôme Boursier Angers, France 11th Paris Hepatology Conference January 16th, 2018 Clinical case Man Man63 63years yearsold, old,referred referredby byhis
More informationBariatric Surgery in NASH Results, indications and contra-indications
Bariatric Surgery in NASH Results, indications and contra-indications Guillaume Lassailly CHRU de Lille Conflit of interest No conflict of interest related to this lecture Contract with: Novartis Gilead
More informationAntifibrotic therapy: between hopes and reality. Fabio Marra Dipartimento di Medicina Sperimentale e Clinica University of Florence, Italy
Antifibrotic therapy: between hopes and reality Fabio Marra Dipartimento di Medicina Sperimentale e Clinica University of Florence, Italy Disclosures Abbvie: consultant fees AstraZeneca: consultant fees
More informationSubject Index. postprandial glycemia and suppression in serum 51 recommendations 119, 120 supplementation pros and cons 118, 119
Acarbose, diabetes prevention trials 32, 33, 40 42 Accelerator hypothesis accelerators beta cell autoimmunity 140, 141, 147, 150, 151 insulin resistance 140, 142 144, 150 obesity 145 148 diabetes risk
More informationLaboratory analysis of the obese child recommendations and discussion. MacKenzi Hillard May 4, 2011
Laboratory analysis of the obese child recommendations and discussion MacKenzi Hillard May 4, 2011 aka: What to do with Fasting Labs The Obesity Epidemic The prevalence of obesity in adolescents has tripled
More informationThe Spectrum of NAFLD. Hepatology Update: The Year in Review Fatty Liver Disease. Hepatology Update: The Year in Review Fatty Liver Disease
Ludwig 1980, Diehl 1988, Lee 1989, Powell 1990, Bacon 1994, Younossi 1997, Matteoni/Younossi 1999, Angulo 1999, Caldwell 1999, Ponawala 2000, Contos 2001, Ong/Younossi 2001, Bugianesi 2002, Ratziu 2002,
More informationNON-ALCOHOLIC STEATOHEPATITIS AND NON-ALCOHOLIC FATTY LIVER DISEASES
NON-ALCOHOLIC STEATOHEPATITIS AND NON-ALCOHOLIC FATTY LIVER DISEASES Preface Zobair M. Younossi xiii Epidemiology and Natural History of NAFLD and NASH 1 Janus P. Ong and Zobair M. Younossi Understanding
More informationStéatopathies métaboliques et diabète. Vlad Ratziu Université Pierre et Marie Curie Hôpital Pitié Salpêtrière, Paris, France
Stéatopathies métaboliques et diabète Vlad Ratziu Université Pierre et Marie Curie Hôpital Pitié Salpêtrière, Paris, France NAFLD : diagnostic framework NAFLD/NASH : a prevalent disease? Individual predisposition
More informationNASH Bench to Bedside
NASH Bench to Bedside October 2006 Anna Mae Diehl, M.D. Gastroenterology Division Duke University NonAlcoholic Fatty Liver Disease Common ~1/4-1/3 1/3 US adults Outcome highly variable Course indolent
More informationNASH UPDATE ON DIAGNOSTICS AND THERAPY. Arun J Sanyal MBBS, MD Virginia Commonwealth University School of Medicine
NASH UPDATE ON DIAGNOSTICS AND THERAPY Arun J Sanyal MBBS, MD Virginia Commonwealth University School of Medicine Conflicts of interest Salaried employee: of VCU Member of Board: McGuire VA Research Institute,
More informationNormal ALT for men 30 IU/L 36% US males abnormal. Abnl ALT. Assess alcohol use/meds. Recheck in 6-8 weeks. still pos
Fatty liver disease Its not just for big boys anymore Ken Flora, MD, FAASLD, FACG, AGAF No disclosures Common situation Normal ALT for men 30 IU/L 36% US males abnormal Normal ALT for women 20 IU/L 28%
More informationEffects of Metformin, Pioglitazone, and Silymarin Treatment on Non- Alcoholic Fatty Liver Disease: A Randomized Controlled Pilot Study
Hepat Mon.2012;12(8):e6099. DOI: 10.5812/hepatmon.6099 KOWSAR www.hepatmon.com Effects of Metformin, Pioglitazone, and Silymarin Treatment on Non- Alcoholic Fatty Liver Disease: A Randomized Controlled
More informationCDHNF & NASPGHAN A Partnership for Research and Education for Children s Digestive and Nutritional Health
CDHNF & NASPGHAN A Partnership for Research and Education for Children s Digestive and Nutritional Health Obesity and NAFLD Definitions: Nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver
More informationOcaliva (obeticholic acid tablets)
Ocaliva (obeticholic acid tablets) Policy Number: 5.01.619 Last Review: 11/2018 Origination: 11/2016 Next Review: 11/2019 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage
More information3/20/2011. Body Mass Index (kg/[m 2 ]) Age at Issue (*BMI > 30, or ~ 30 lbs overweight for 5 4 woman) Mokdad A.H.
U.S. Adults: 1988 Nineteen states with 10-14% 14% Prevalence of Obesity (*BMI > 30, or ~ 30 lbs overweight for 5 4 woman) Metabolic John P. Cello, MD Professor of Medicine and Surgery, University of California,
More informationUltrasound showing. Biopsies. Criteria for Dx of NASH. macrovesicular steatosis (zone III) Bright echogenic liver. Definition of NASH
Definition of NASH Nonalcoholic steatohepatitis (NASH) is the term used to describe the distinct clinical entity in which patients lack a history of significant alcohol consumption but have liver biopsy
More informationNonalcoholic fatty liver disease: A manifestation of the metabolic syndrome
REVIEW CME CREDIT CHIN HEE KIM, MD Center for Liver Diseases Inova Fairfax Hospital, Falls Church, VA ZOBAIR M. YOUNOSSI, MD, MPH * Center for Liver Diseases Inova Fairfax Hospital, Falls Church, VA; Executive
More informationSYSTEMATIC REVIEW. G. Musso & M. Cassader & F. Rosina & R. Gambino
Diabetologia (2012) 55:885 904 DOI 10.1007/s00125-011-2446-4 SYSTEMATIC REVIEW Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease
More informationClinical Study Hepatic Steatosis, Carbohydrate Intake, and Food Quotient in Patients with NAFLD
International Endocrinology Volume 213, Article ID 428542, 4 pages http://dx.doi.org/1.1155/213/428542 Clinical Study Hepatic Steatosis, Carbohydrate Intake, and Food Quotient in Patients with NAFLD Concepcion
More informationEvercore ISI Presentation- Madrigal
Evercore ISI Presentation- Madrigal Forward-Looking Statements Any statements, other than statements of historical facts, made in this presentation regarding our clinical studies and our research and development
More informationFirst European NAFLD-NASH Summit European Parliament, Brussels, May 31 st NAFLD/NASH : an expanding burden on liver health
First European NAFLD-NASH Summit European Parliament, Brussels, May 31 st 2017 NAFLD/NASH : an expanding burden on liver health Vlad Ratziu, Université Pierre et Marie Curie, Hôpital Pitié Salpêtrière,
More informationUpdate On Diabetic Dyslipidemia: Who Should Be Treated With A Fibrate After ACCORD-LIPID?
Update On Diabetic Dyslipidemia: Who Should Be Treated With A Fibrate After ACCORD-LIPID? Karen Aspry, MD, MS, ABCL, FACC Assistant Clinical Professor of Medicine Warren Alpert Medical School of Brown
More informationNon-Alcoholic Fatty Liver Disease (NAFLD)
HEPATO-PANCREATO-BILIARY STOMACH CANCER PROGRAM Non-Alcoholic Fatty Liver Disease (NAFLD) Steatosis and Non-Alcoholic Steatohepatitis (NASH) Management Recommendations UCSF Fresno Department of Surgery
More informationAbnormal LFTs and NAFLD. Dr William Alazawi MA(Cantab) PhD MRCP Senior Lecturer and Consultant in Hepatology Queen Mary, University of London
Abnormal LFTs and NAFLD Dr William Alazawi MA(Cantab) PhD MRCP Senior Lecturer and Consultant in Hepatology Queen Mary, University of London Does Liver Disease Matter? Mortality in England & Wales Liver-related
More informationHepatobiliary lipids איך טיפול נולד... from bench to bedside. Fred M Konikoff, MD, MSc, FAASLD
Hepatobiliary lipids איך טיפול נולד... from bench to bedside Fred M Konikoff, MD, MSc, FAASLD Institute of Gastroenterology and Hepatology, Meir Medical Center, Kfar Saba, and Research Laboratory of Cholesterol
More informationEASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease
Received: November 4, 2015 Accepted: November 4, 2015 Published online: April 8, 2016 2016 The Author(s) Published by S. Karger GmbH, Freiburg 1662 4033/16/0092 0065$39.50/0 This article is licensed under
More informationNAFLD AND TYPE 2 DIABETES
NAFLD AND TYPE 2 DIABETES Sonia Caprio, MD STOPNASH Symposium on the Origin and Pathways of Nonalcoholic Steatohepatitis Washington 7, 215 Global Projection of Diabetes Hossain P et al. N Engl J Med 27;356:213
More informationLavine, MD, PhD; 4 Anna Mae Diehl, MD; 5 Elizabeth M. Brunt, MD; 6 Kenneth Cusi, MD; 7 Michael Charlton, MD; 8 Arun J. Sanyal, MD
Page 1 of 59 The Diagnosis and Management of Non-alcoholic Fatty Liver Disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and
More informationWhat you need to know about liver disease
What you need to know about liver disease Bob Grover Consultant Gastroenterologist and Hepatologist The Hillingdon Hospitals NHS Foundation Trust Overview Liver disease in the UK Alcohol Fatty liver Hepatitis
More informationNon-Alcoholic Fatty Liver Disease
Non-Alcoholic Fatty Liver Disease Varun Saxena, MD MAS Gastroenterology and Hepatology Kaiser Permanente South San Francisco Assistant Clinical Professor University of California San Francisco January
More informationReproductive Health in Non Alcoolic Fatty Liver Disease (NAFLD)
Reproductive Health in Non Alcoolic Fatty Liver Disease (NAFLD) Pr Sophie Christin-Maitre Reproductive Endocrine Unit, Hôpital Saint-Antoine, AP-HP Université Pierre et Marie Curie INSERM U933 Paris, France
More informationNASH: What is It? Categories of NAFLD. Welcome to NASHville. 1 st described 1980 by Ludwig, et al. Part of Nonalcoholic Fatty Liver Disease (NAFLD)
Welcome to NASHville Vicki Wettig, M.S.N., CRNP Lancaster Gastroenterology, Inc. NASH: What is It? 1 st described 1980 by Ludwig, et al. Part of Nonalcoholic Fatty Liver Disease (NAFLD) spectrum of fatty
More information