Expert faculty summarize key NAFLD/NASH studies from this important annual conference. Use these slides to review data on noninvasive screening, clinical outcomes, emerging treatments.
Ira M. Jacobson, MD
Philip N. Newsome, PhD, FRCPE
Format: Microsoft PowerPoint (.ppt)
File Size: 421 KB
Released: December 3, 2018
NAFLD is a vast topic and recently gaining a lot of importance. Fatty liver, NASH, are other topics discussed here. sleissenger, sheila sherlock and Harrisons are used for reference
An updated review on nonalcoholic steatohepatitis, epidemiology, pathology, diagnosis, treatment modalities and current clinical trials are reviewed.
New England Journal of Medicine review article from November 2017 entitled "Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis" was extensively cited, please see references on the last slide (DOI: 10.1056/NEJMra1503519).
This is purely for educational purposes; I do not diagnose, treat, or offer patient-specific advice by sharing these slides.
NAFLD is a vast topic and recently gaining a lot of importance. Fatty liver, NASH, are other topics discussed here. sleissenger, sheila sherlock and Harrisons are used for reference
An updated review on nonalcoholic steatohepatitis, epidemiology, pathology, diagnosis, treatment modalities and current clinical trials are reviewed.
New England Journal of Medicine review article from November 2017 entitled "Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis" was extensively cited, please see references on the last slide (DOI: 10.1056/NEJMra1503519).
This is purely for educational purposes; I do not diagnose, treat, or offer patient-specific advice by sharing these slides.
Slides From Hot Topics in NASH:New Strategies for the Diagnosis of NASH.2019hivlifeinfo
Slides From Hot Topics in NASH: New Strategies for the Diagnosis of NASH
xpert faculty present key data on current and emerging NASH treatment options for your patients.
Rita Basu, MD
Wing-Kin Syn, MBChB, PhD, FACP, FRCP
Format: Microsoft PowerPoint (.ppt)
File Size: 3.84 MB
Released: February 11, 2019
Slides From Hot Topics in NASH:New Strategies for the Diagnosis of NASH.2019hivlifeinfo
Slides From Hot Topics in NASH: New Strategies for the Diagnosis of NASH
xpert faculty present key data on current and emerging NASH treatment options for your patients.
Rita Basu, MD
Wing-Kin Syn, MBChB, PhD, FACP, FRCP
Format: Microsoft PowerPoint (.ppt)
File Size: 3.84 MB
Released: February 11, 2019
Androgens & Cardiovascular Diseases in Women: From Basic Research to Clinical...InsideScientific
Join Dr. Licy Yanes-Cardozo as she expands on her research exploring the role of androgens on cardiovascular physiology in cis and transgender patients.
Women have higher plasma concentrations of androgens than estrogens, yet the role of androgens in physiological processes and diseases is not completely understood. High levels of androgens in women are associated with a negative cardiometabolic profile, whereas in men, low levels of androgens are associated with an increased incidence of cardiovascular diseases.The biology behind androgens’ sex difference is not completely understood.
In this webinar, Dr. Yanes-Cardozo discusses two clinical situations that are associated with high levels of androgens. Polycystic Ovary Syndrome (PCOS), the most common endocrine disorder in reproductive-aged women, is associated with a modest elevation of plasma levels of androgens. In transmen individuals (female to male), plasma concentrations of androgens are elevated to achieve similar levels found in cisgender men and much higher than in PCOS women. The role that these two different plasma concentrations play in cardiovascular physiology and pathophysiology remains unclear. Gaps and opportunities in basic research and clinical practice are highlighted.
Key Topics Include:
- Review the key role of androgens in cardiovascular pathophysiology
- Discuss potential mechanisms by which androgens mediate a deleterious cardiometabolic profile in females
- Interpret gaps and opportunities in basic and clinical practice in conditions of androgen excess
Fase III que utiliza Nab-Paclitaxel + Carboplatino y Pembrolizumab en NSCLC escamoso. El hazard ratio favorece a Nab paclitaxel en el análisis de subgrupos.
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Дискуссии о здоровом старении с ВИЧ /Key Slides on Healthy Aging With HIV.2022hivlifeinfo
Дискуссии о здоровом старении с ВИЧ
Узнайте о медицинских и немедицинских проблемах, с которыми сталкиваются стареющие пациенты с ВИЧ, включая дополнительные проблемы, с которыми сталкиваются пожилые женщины и пожилые люди, живущие в условиях ограниченных ресурсов.
Основы ведения АРТ у многократно леченных пациентов 2022 / Foundations of ART...hivlifeinfo
Основы ведения АРТ у многократно леченных пациентов (2022)
Тактики ведения пациентов с большим опытом лечения, включая анализ резистентности, последние рекомендации и данные по новым схемам АРТ
Современное лечение и профилактика ВИЧ : передовые стратегии лечения у пациен...hivlifeinfo
Стратегии смены АРТ у пациентов с вирусной супрессией, включая смену АРТ при резистентности, рекомендации по инъекционным препаратам длительного действия , смена АРТ до или во время беременности
Ключевые слайды по индивидуальному выбору АРТ / Key Slides on Individualized ...hivlifeinfo
Слайды с последними данные и рекомендациями по выбору АРТ, как для пациентов, ранее не получавших лечения, так и пациентов с вирусологической супрессией. Оценки разных вариантов лечения, индивидуализация АРТ для женщин детородного возраста и во время беременности, пациентов с опортунистическими инфекциями и новые данные об исследовательских стратегиях АРТ.
Современное лечение ВИЧ: новые парадигмы в АРТ / Contemporary Management of H...hivlifeinfo
Набор слайдов c рассмотрением важных вопросов об АРТ первого ряда, арв-препаратами пролонгированного действия и схемами АРТ с двумя препаратами, акцент в публикации на роль новых стратегий.
Современное лечение ВИЧ: модификация АРТ у пациентов с вирусологической супре...hivlifeinfo
Современное лечение ВИЧ: модификация АРТ у пациентов с вирусологической супрессией (2021) / Contemporary Management of HIV: Modifying ART in Virologically Suppressed Patients 2021
Key Slides on ART for HIV : Evolving Concepts and Innovative Strategies.2020hivlifeinfo
Expert-authored slides on evolving ART concepts, including simplification to 2-drug therapy, ART safety during pregnancy, weight gain, and long-acting injectable ART.
File Size: 580 KB
Released: October 20, 2020
Современное лечение ВИЧ: новые подходы к оптимизации АРТ/Contemporary Managem...hivlifeinfo
Вопросы, связанные с АРТ первого ряда, смена арв-стратегии для пациентов с вирусной супрессией, акцентом на возрастающую роль новыхантиретровирусных стратегий.
Clinical Impact of New Data From AIDS 2020hivlifeinfo
current ART in principal populations, including older patients and women who become pregnant; metabolic outcomes during ART; HIV and COVID-19; investigational ART strategies; and HIV prevention.
Слайдсет о новом в лечении ВИЧ.Key Slides on What’s Hot in HIV Treatment.2020 hivlifeinfo
Expert-authored slides on the latest issues relating to HIV care, featuring patient cases and considerations for optimal treatment approaches. Topics include integrating newer ARVs, individualizing ART for women of childbearing potential and during pregnancy, adverse events during ART, and anticipated roles of emerging ART strategies.
Гиперлипопротеидемия(а) как опасное генетически обусловленное нарушение липид...hivlifeinfo
Гиперлипопротеидемия(а) как опасное генетически обусловленное нарушение липидного обмена и фактор риска атеротромбоза и сердечно-сосудистых заболеваний
Липопротеид(а) [Лп(а)] представляет собой сложный надмолекулярный комплекс, принадлежащий к апоВ100 содержащим липопротеидам. Лп(а) состоит из ЛНП-подобной частицы, в которой молекула апобелка В100 ковалентно связана дисульфидной связью с уникальной полиморфной молекулой апобелка(а). Концентрация Лп(а) генетически контролируется, при этом варьирует в очень широком диапазоне. Повышенный уровень Лп(а) является независимым фактором риска атеросклероза коронарных, сонных и периферических артерий, ИБС и стеноза аортального клапана, сопутствующих сердечно-сосудистых осложнений, а также осложнений после операций реваскуляризации миокарда. Несмотря на это, уровень Лп(а) по-прежнему не учитывается в стратификации риска сердечно-сосудистых заболеваний. Отчасти, это может быть связано с тем, что ни современная лекарственная терапия, ни новые поколения биологических гиполипидемических препаратовтерапия практически не влияют на концентрацию Лп(а), за исключением 20-30% снижения Лп(а) никотиновой кислотой и ингибиторами пропротеиновой конвертазы субтилизин-кексин 9 типа (PCSK9).
Лекция освящает современные представления о Лп(а), как факторе риска сердечно-сосудистых заболеваний, возможности и целесообразности его определения, а также посвящена современным возможностям коррекции гиперлипопротеидемии(а).
Физическая активность и физические тренировки как метод профилактики сердечно...hivlifeinfo
Чушкин М.И., Мандрыкин С.Ю., Карпина Н.Л., Попова Л.А. Физическая активность и физические тренировки как метод профилактики сердечно-сосудистых заболеваний. Кардиология. 2018;58(9S):10-18
Большое число данных свидетельствует, что функциональные возможности кардиореспираторной системы являются не менее важным фактором прогноза летальности, чем курение, артериальная гипертензия, ожирение, гиперхолестеринемия, СД. Пациенты с большей физической активностью имеют значительно меньший риск ССЗ, чем пациенты, ведущие неактивный образ жизни. В данном обзоре авторы показали возможности оценки физической активности и основные положения назначения физических тренировок для сохранения и повышения функциональных возможностей кардиореспираторной системы.
Key Slides on Individualizing ART Management Based on Treatment Safety and To...hivlifeinfo
Обзор последних рекомендаций DHHS , индивидуализация лечения в отдельных группах пациентов, минимизация побочных эффектов и межлекарственных взаимодействий
Современное лечение ВИЧ.Обобщённые данные с конференции CROI 2020 / Contempor...hivlifeinfo
Современное лечение ВИЧ.Обобощенные данные с конференции CROI 2020 / Contemporary Management of HIV.Integrating New Data From CROI 2020
Широкий спектр вопросов, включая стратегии АРТ на поздних стадихя заболевания, менеджмент ожирения, метаболические исходы АРТ, данные по АРТ во время беременности и пр
Format: Microsoft PowerPoint (.ppt)
File Size: 554 KB
Released: April 14, 2020
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Clinical Impact of New NAFLD/NASH Data From San Francisco 2018
1. Clinical Impact of New NAFLD/NASH Data From
San Francisco 2018
This program is supported by educational grants from
AbbVie and Gilead Sciences
CCO Independent Conference Coverage*
of The Liver Meeting 2018; November 9-13, 2018; San Francisco, California
*CCO is an independent medical education company that provides state-of-the-art medical information to
healthcare professionals through conference coverage and other educational programs.
2. Please feel free to use, update, and share some or all of these slides in
your noncommercial presentations to colleagues or patients
When using our slides, please retain the source attribution:
These slides may not be published, posted online, or used in
commercial presentations without permission. Please contact
permissions@clinicaloptions.com for details
About These Slides
Slide credit: clinicaloptions.com
3. Faculty
Ira M. Jacobson, MD
Director of Hepatology
Department of Medicine
NYU School of Medicine
New York, New York
Philip N. Newsome, PhD, FRCPE
Professor of Hepatology
University of Birmingham
Birmingham, United Kingdom
4. Disclosures
Ira M. Jacobson, MD, has disclosed that he has received funds for
research support and consulting fees from AbbVie, Bristol-Myers Squibb,
Enanta, Genfit, Gilead Sciences, Intercept, Janssen, Merck, Novo Nordisk,
Spring Bank, and Trek Therapeutics.
Philip N. Newsome, PhD, FRCPE, has disclosed that he has received
consulting fees from Afimmune, Boehringer Ingelheim, Gilead Sciences,
Intercept, Novo Nordisk, Pfizer, and Shire; has received funds for research
support from Boehringer Ingelheim; and has served on speaker bureaus
for Intercept and Norgine.
6. Detection of Active NASH and Advanced Fibrosis With
FibroScan-Based Scoring
Prospective, multicenter study of patients undergoing liver biopsy for
suspected NASH (N = 335)
Score based on fibrosis, steatosis, and inflammation (LSM, CAP, AST)
used to detect patients with active NASH and advanced fibrosis
(NAS ≥ 4, fibrosis level F ≥ 2)
‒ Performance assessed by AUROC
‒ Validated internally by bootstrap
‒ Cutoffs determined in derivation cohort
‒ External validation: French bariatric surgery, Malaysian NAFLD,
US screening cohorts
Sasso. AASLD 2018. Abstr 140. Slide credit: clinicaloptions.com
7. Validation of Score for Detection of Active NASH and
Advanced Fibrosis
Sasso. AASLD 2018. Abstr 140. Slide credit: clinicaloptions.com
Good performance in derivation and validation cohorts
‒ In multiple clinical settings (screening, bariatric surgery, NAFLD)
‒ In multiple geographical areas (Asia, Europe, United States)
Derivation Cohort External Validation Cohorts
Characteristic
Development
Population
(N = 335)
Bootstrap
Validation
(N = 335)
Malaysian
NAFLD Cohort
(N = 231)
US Screening
Cohort
(N = 193)
French Bariatric
Surgery Cohort
(N = 110)
All
(N = 534)
NASH, NAS ≥ 4, F ≥ 2
prevalence, n (%)
166 (50) (44-55)* 53 (23) 24 (12) 17 (15) 96 (18)
VCTE + CAP + AST
AUROC (95% CI)
0.83
(0.78-0.87)
0.83
(0.78-0.87)
0.85
(0.80-0.91)
0.91
(0.86-0.96)
0.93
(0.89-0.98)
0.88
(0.85-0.91)
*95% CI for prevalence.
8. NIS4: Detection of Active NASH and Advanced Fibrosis
With Biomarker-Based Scoring
Sanyal. AASLD 2018. Abstr 142. Slide credit: clinicaloptions.com
NIS4: score based on biomarkers miR-34a, alpha-2-macroglobulin,
YKL-40, and A1C used to detect patients with active NASH and
advanced fibrosis (NAS ≥ 4, fibrosis level F ≥ 2)
Baseline data from GOLDEN and RESOLVE-IT trials (N = 714)
‒ Training set: 220 patients from GOLDEN trial
‒ Validation set: first 467 patients screened for inclusion in RESOLVE-IT
9. Validation of NIS4 for Detection of Active NASH and
Advanced Fibrosis
For overall population, NIS4 AUROC = 0.83 (95% CI: 0.80-0.86)
‒ Consistently good performance across the clinical spectrum of NAFLD,
regardless of obesity, metabolic syndrome, T2DM status, or sex
Sanyal. AASLD 2018. Abstr 142. Slide credit: clinicaloptions.com
Group Subgroup n
Prevalence
NAS ≥ 4 and F ≥ 2, %
AUC
(95% CI)
Obesity BMI ≤ 30 224 45 0.794 (0.733-0.849)
BMI > 30 490 54 0.838 (0.804-0.873); P = .204
Diabetes No 439 44 0.830 (0.790-0.867)
Yes 275 61 0.801 (0.748-0.854); P = .382
Age ≤ 55 yrs 361 42 0.804 (0.758-0.848)
> 55 yrs 353 59 0.833 (0.791-0.871); P = .358
Sex Female 369 50 0.841 (0.802-0.881)
Male 345 51 0.813 (0.767-0.855); P = .345
10. Sequential Algorithms to Detect Advanced Fibrosis due
to NASH
Study of baseline data from
STELLAR trials (N = 3202) to
determine performance of
sequential combinations of
noninvasive tests in diagnosing
F3/F4 liver fibrosis
Liver biopsy assessment
‒ 41% fibrosis stage F4 (n = 1283)
‒ 30% fibrosis stage F3 (n = 979)
Algorithm based on noninvasive
tests used low cutoff for
sensitivity (to rule in F0-F2) and
high cutoff for specificity (to
rule in F3/F4)
‒ Novel cutoffs from STELLAR
study: FIB-4 (1.23, 2.10), ELF
(9.35, 10.24), FibroScan (9.6,
14.53 kPa)
‒ Published cutoffs: FIB-4 (1.30,
2.67), ELF (9.8, 11.3), FibroScan
(9.9, 11.4 kPa)
Younossi. AASLD 2018. Abstr LB-10. Slide credit: clinicaloptions.com
11. Sequential Algorithms to Detect Advanced Fibrosis due
to NASH: Results
Single tests (either FIB-4, ELF, or FibroScan) led to up to 50%
indeterminate results
Algorithm using 3 sequential tests (FIB-4, then ELF, then FibroScan) led
to 9% to 10% indeterminate results
Younossi. AASLD 2018. Abstr LB-10. Slide credit: clinicaloptions.com
Outcome, % (95% CI)
Test Cutoffs F3/F4, % Sensitivity Specificity PPV NPV Indeterminate Misclassified
Novel cutoffs
(n = 639)
71 75 (71-79) 82 (76-87) 91 (88-94) 58 (52-64) 9 (7-11) 23 (20-26)
Published cutoffs
(n = 639)
71 64 (60-69) 93 (88-96) 95 (92-97) 52 (46-57) 10 (7-12) 28 (24-31)
13. NAFLD Prevalence in Lean vs Obese Adults With or
Without Metabolic Abnormalities
Slide credit: clinicaloptions.com
Study of adults in NHANES III from 1988-1994 followed through 2011
‒ Obese defined as BMI > 30 and high waist circumference
(> 102 cm for men, > 88 cm for women)
‒ Lean defined as BMI < 25 and normal waist circumference
(≤ 90 cm for men, ≤ 80 cm for women)
Golabi. AASLD 2018. Abstr 179.
NAFLD Prevalence, % All
Obese
(n = 2952)
Lean
(n = 3242)
All patients 19.6 39.4 7.7
Any metabolic abnormalities 18.1 38.4 5.5
No metabolic abnormalities 1.5 1 2.2
14. Lean, Metabolically Normal Adults With NAFLD:
Mortality
Characteristic Deaths, n
Unadjusted
Mortality, % (95% CI)
P
Value*
Age-Adjusted Mortality,
% (95% CI)
P
Value*
Deaths among lean patients with
NAFLD
Without metabolic abnormalities
With metabolic abnormalities
57
8
49
13.83 (8.80 to 18.86)
8.72 (-0.37 to 17.81)
16.60 (11.16 to 22.03)
NA
NA
.1459
18.32 (12.09 to 24.56)
15.01 (3.09 to 26.92)
19.90 (13.19 to 26.61)
NA
NA
.4399
CV deaths among lean patients with
NAFLD
Without metabolic abnormalities
With metabolic abnormalities
13
0
13
2.89 (9.14 to 4.87)
0
4.46 (1.79 to 7.13)
NA
NA
.0020
3.71 (1.76 to 5.66)
0
3.71 (1.73 to 5.69)
NA
NA
.0005
*vs lean adults without metabolic abnormalities.
In lean NAFLD adults without any component of metabolic syndrome,
no increased overall or CV-related mortality vs lean non-NAFLD
controls
‒ Median follow up: 18.9 yrs
Golabi. AASLD 2018. Abstr 179. Slide credit: clinicaloptions.com
15. Poorer Patient-Reported Outcomes in NASH and With
More Advanced Fibrosis
Younossi. AASLD 2018. Abstr 1683. Slide credit: clinicaloptions.com
Design
Analysis of NASH patients with bridging
fibrosis or compensated cirrhosis (NASH CRN
stages F3-F4) enrolled in phase III STELLAR
trial evaluating ASK1 inhibitor selonsertib
(N = 1667)
PROs collected before treatment initiation
‒ Chronic Liver Disease Questionnaire (CLDQ
NAFLD-NASH)
‒ EQ-5D
‒ Short Form-36 (SF-36)
‒ Work Productivity and Activity Index
(WPAI:SHP)
Results
Physical health–related PROs significantly
worse with NASH patients vs population
norms (all P < .05)
F4 cohort had significantly poorer PROs vs F3
in most questionnaire components (P < .02)
‒ Average impairment difference for F4 vs F3
across all PROs: -1.6% to -4.7% (P < .05)
‒ Most pronounced impairment in CLDQ
NAFLD-NASH’s Activity and Worry domains
16. Independent Predictors of Poorer Patient-Reported
Outcomes in NASH
Younossi. AASLD 2018. Abstr 1683. Slide credit: clinicaloptions.com
Independent Predictors of
Poorer Scores in NASH Patients*
Beta, % of PRO
Range Size
Age, per yr 0.15 to 0.53
Male sex 2.1 to 9.8
Black vs white -14.9 to -7.8
Asian vs white 4.3 to 10.2
US enrollment 3.2 to 10.2
Current smoker -7.1 to -3.7
BMI, per kg/m2 -0.80 to -0.18
Diabetes mellitus -4.6 to -3.1
Asthenic conditions -7.5 to -6.1
GI disorders -7.3 to -2.8 *All P < .01 after stepwise selection in multiple models.
Independent Predictors of
Poorer Scores in NASH Patients*
Beta, % of PRO
Range Size
Musculoskeletal and connective
tissue disorders
-11.6 to -2.4
Nervous system disorders -5.7 to -2.7
Psychiatric disorders -13.3 to -4.9
Albumin, per g/dL 4.7 to 10.9
Apolipoprotein A1, per mg/dL 0.05 to 0.07
CRP, per mg/dL -3.2 to -2.0
Haptoglobin, per mg/dL -0.03 to -0.02
A1C, per % -2.2 to -1.4
17. Bariatric Surgery in Patients With Cirrhosis, Including
NASH Cirrhosis
Single-center, longitudinal study of patients with compensated or
decompensated cirrhosis (N = 60,543)
Griffin. AASLD 2018. Abstr 218. Slide credit: clinicaloptions.com
Patient Characteristic, %
Cirrhosis With Bariatric Surgery
(n = 292)
Cirrhosis Without Bariatric Surgery
(n = 29,987)
Female 73 38
NASH cirrhosis 16 3
Alcoholic cirrhosis 31 31
Decompensated cirrhosis 71 72
18. Lower Survival With Bariatric Surgery in Patients With
Cirrhosis, Including NASH Cirrhosis
Bariatric surgery also a predictor of mortality among compensated and decompensated
cirrhotic patients (obesity not significant)
‒ HR: 1.3; 95% CI 1.12-1.62; P = .002
Slide credit: clinicaloptions.comGriffin. AASLD 2018. Abstr 218.
0
20
40
60
80
Survival(%)
57.9
62.8
100
Patients With Bariatric Surgery Patients Without Bariatric Surgery
P < .04
5-Yr Survival Among Patients With Cirrhosis
19. Bariatric Surgery and Regression of NASH Fibrosis
Multicenter, prospective study of long-term impact of bariatric surgery in morbidly
obese NASH patients (N = 190)
Lassally. AASLD 2018. Abstr 70. Slide credit: clinicaloptions.com
Patient Characteristic Patients
Median age, yrs (IQR) 46.5 (38.3-54.3)
Female, % 65.8
Median BMI (IQR) 46.9 (42.9-52.3)
Median ALT (IQR) 45 (32-62)
Median γGT (IQR) 53.5 (35-86.8)
Median A1C, mmol/mol (IQR) 6.9 (5.9-8.8)
Median liver fat amount, % (IQR) 60 (40-75)
Median NAS (IQR) 5 (4-5)
Median Score Patients, %
Brunt activity score
Mild (1)
Moderate (2)
Severe (3)
68.95
23.68
23.68
METAVIR fibrosis score
F0
F1
F2
F3
F4
37.36
30.77
16.46
11.54
3.85
20. Disappearance of NASH and Regression of Fibrosis
Following Bariatric Surgery
NASH disappearance in 85% of
patients at Yrs 1 and 5
Fibrosis by Brunt and METAVIR
score significantly reduced at
Yrs 1 and 5 vs baseline
Patients without fibrosis
regression experienced less
weight loss, higher insulin
resistance (HOMA-IR), and
higher NAS following surgery
Lassally. AASLD 2018. Abstr 70. Slide credit: clinicaloptions.com
METAVIR
Fibrosis Stage
Patients, %
BL Yr 1 Yr 5
F0 37.36 45.69 63.49
F1 30.77 30.17 22.22
F2 16.48 12.93 3.17
F3 11.54 9.48 9.52
F4 3.85 1.72 1.59
P = .01 baseline vs Yr 1; P = .003 Yr 1 vs Yr 5.
21. Cirrhosis and HCC Risk: Association With Steatosis
and ALT
Retrospective study of adults with > 1 ALT test and abdominal imaging within
VA hospital system (N = 78,892)
‒ Excluded patients with:
‒ Cirrhosis or HCC before or within 1 yr of first ALT test
‒ HCV or HBV infection
‒ Excessive alcohol use
‒ Rare hepatic conditions (including Wilson’s disease, primary biliary cirrhosis,
primary sclerosing cholangitis, autoimmune hepatitis, or hereditary
hemochromatosis)
Subjects followed to end of 2015 or to HCC, cirrhosis, or death
Natarjan. AASLD 2018. Abstr 143. Slide credit: clinicaloptions.com
22. Characteristic No Steatosis, Normal ALT Steatosis, Normal ALT Steatosis, High ALT
Age, mean (SD) 58.1 (10.7) 56.4 (10.3) 53.3 (12.1)
Male, n (%) 22,711 (92.2) 10,478 (91.8) 39,664 (92.6)
Race/ethnicity, n (%)
White
Black
Hispanic
Other
16,062 (65.2)
4719 (19.2)
1078 (4.4)
483 (2.0)
7532 (66.0)
1752 (15.4)
850 (7.5)
271 (2.4)
30,404 (71.0)
4061 (9.5)
3512 (8.2)
1362 (3.2)
BMI, n (%)
< 30
≥ 30
15,539 (63.1)
9097 (36.9)
5188 (45.5)
6221 (54.5)
15,298 (35.7)
25,748 (64.3)
Comorbidity, n (%)
DM
Hypertension
Dyslipidemia
CAD
6363 (25.8)
17,794 (72.2)
16,317 (66.2)
5538 (22.5)
3867 (33.9)
8576 (75.2)
8135 (71.3)
2588 (22.7)
14,490 (33.8)
31,467 (73.4)
30,524 (71.2)
8273 (19.3)
Healthcare use, n (%) 21,987 (89.2) 10,340 (90.6) 40,430 (94.4)
Baseline Characteristics
Natarjan. AASLD 2018. Abstr 143. Slide credit: clinicaloptions.com
23. Outcome
Cirrhosis HCC
Patients,
n
Incidence,
n
Follow-up,
PYs
Adjusted Risk
(95% CI)
Incidence,
n
Follow-up,
PYs
Adjusted Risk
(95% CI)
No steatosis,
normal ALT
24,638 445 184,591 Ref 18 186,484 Ref
Steatosis,
normal ALT
11,409 225 343,688 1.1 (1.0-1.3) 9 91,542 1.0 (0.3-3.0)
Steatosis,
high ALT
42,845 1694 90,388 2.2 (2.0-2.5) 117 350,398 3.8 (1.9-7.4)
Risk of Cirrhosis and HCC in Patients With Steatosis and
Normal ALT
Natarjan. AASLD 2018. Abstr 143. Slide credit: clinicaloptions.com
Cumulative Incidence/1000 PYs
(95% CI)
No Steatosis,
Normal ALT
Steatosis,
Normal ALT
Steatosis,
High ALT
Cirrhosis 2.41 (2.19-2.65) 2.16 (2.18-2.84) 4.93 (4.70-5.17)
HCC 0.1 (0.06-0.15) 0.1 (0.05-0.19) 0.33 (0.28-0.40)
30. CONTROL: Obeticholic Acid in Patients With NASH
Double-blind, placebo-controlled,
phase II study
‒ Obeticholic acid: FXR agonist
Through Wk 16, patients with vs
without cirrhosis (F4 vs F1-F3)
showed no trend for differences in:
‒ ALT
‒ Bilirubin
‒ Platelets
‒ INR
‒ Change in C4 from baseline
Halegoua-De Marzio. AASLD 2018. Abstr 71. Slide credit: clinicaloptions.com
Adults with NASH,
F1-F4 fibrosis,
without hepatic
decompensation
(N = 84)
Obeticholic Acid 5 mg/day*
(n =20)
Obeticholic Acid 25 mg/day*
(n = 22)
Obeticholic Acid 10 mg/day*
(n = 21)
Placebo*
(n = 21)
Wk 16
*Plus atorvastatin 10 mg Wk 4 through Wk 8, then 20 mg through Wk 12,
then titrated up or down depending on clinical signs until Wk 16
32. FLIGHT-FXR: Tropifexor (TXR) in Patients With NASH
FLIGHT-FXR: 3-part randomized, placebo-controlled,
double-blind, dose-ranging phase IIb study
‒ TXR: FXR agonist
Current analysis reports pooled
data from Parts A and B
‒ Part C (not shown) ongoing
Sanyal. AASLD 2018. Abstr LB-23. Slide credit: clinicaloptions.com
Part A
Adults with NASH*, weighing
40-150 kg with liver fat ≥ 10%
by MRI-PDFF
(N = 77)
TXR 10 μg QD (n = 14)
Wk 12
TXR 30 μg QD (n = 16)
TXR 60 μg QD (n = 16)
TXR 90 μg QD (n = 15)
Placebo QD (n = 16)
Part B
Adults with NASH*, weighing
40-150 kg with liver fat ≥ 10%
by MRI-PDFF
(N = 121)
TXR 60 μg QD (n = 21)
TXR 90 μg QD (n = 70)
Placebo QD (n = 30)
*NASH defined as F1-F3 on biopsy obtained within 2 yrs of randomization, no other chronic liver disease, with
elevated ALT; or by phenotype (elevated ALT, BMI ≥ 27 in non-Asians or ≥ 23 in Asians, with T2DM).
Efficacy
endpoints
Safety
endpoints
33. Efficacy of TXR in Overall Population and in Subgroup of
Patients With Biopsy-Proven NASH at Wk 12
AEs similar among arms; TXR well tolerated with few grade 3/4 AEs or SAEs
‒ 9% of pts on TXR 90 μg QD discontinued or reduced dose for AEs
‒ TXR associated with mild dose-related rise in LDL-C and mild reduction in HDL-C
Sanyal. AASLD 2018. Abstr LB-23. Slide credit: clinicaloptions.com
Relative Change
vs BL,* % (n)
Biopsy-Proven NASH Only Phenotypic and Biopsy-Proven NASH
Placebo
(n = 18)
TXR 60 μg
(n = 12)
TXR 90 μg
(n = 35)
Placebo
(n = 46)
TXR 60 μg
(n = 37)
TXR 90 μg
(n = 85)
FGF19 +46 (12) +232 (10) +556 (34) + 37 (37) + 319 (34) +528 (74)
ALT -15.5 (17) -23.7 (12) -26.9 (32) -15.5 (45) -21.2 (36) -24.0 (73)
GGT -10.5 (17) -46.5 (12) -56.5 (34) -9.2 (45) -43.3 (36) -56.6 (78)
Liver fat content
by MRI-PDFF
-1.8 (14) -7.2 (12) -12.5 (28) -9.8 (41) -16.9 (36) -15.6 (63)
*Change in ALT, GGT, HFF reported as geometric mean of relative change at Wk 12 vs BL, FGF19 as 4 hrs post-dose vs pre-dose at Wk 6.
35. NGM282 in Patients With NASH
Multicenter, dose-finding phase II study of NGM282
‒ NGM282: FGF19 analogue
Harrison. AASLD 2018. Abstr 104. Slide credit: clinicaloptions.com
Patients with biopsy-confirmed
NASH, NAS ≥ 4*, stage 1-3 fibrosis,
liver fat ≥ 8% by MRI-PDFF
(N = 43)
*≥ 1 point in each component of NAS.
NGM282
1 mg SC QD†
Followed through
Wk 18
Wk 12
NGM282
3 mg SC QD†
†Option for rosuvastatin 20 mg at
Wk 2 if 10 mg/dL LDL-C increase
observed; titrated up to 40 mg in
Wks 4-8 if LDL-C remained above BL.
36. NGM282: Liver Fat Content by MRI-PDFF at Wk 12
Harrison. AASLD 2018. Abstr 104. Slide credit: clinicaloptions.com
Change in Liver Fat Content From BL, %
NGM282 1 mg*
(n = 24)
NGN282 3 mg*
(n = 19)
Absolute change -10.9 -11.2
≥ 5% absolute reduction 92 100
Normalized LFC† 33 63
Relative change -57 -67
≥ 30% relative reduction 92 100
*All absolute and relative changes P < .001 vs baseline.
†Normalized LFC defined as absolute MRI-PDFF ≤ 5%.
37. Patients with NASH resolution (n = 19): 16% Patients with NASH resolution (n = 19): 11%
NGM282: Fibrosis at Wk 12
Harrison. AASLD 2018. Abstr 104. Slide credit: clinicaloptions.com
NGM282 1 mg NGM282 3 mg
Fibrosis Stage at Baseline
Patients, % (n = 24)
16%
42%
38%
4%
F1
F2
F3
F4
Fibrosis Response at Wk 12
Patients, %
25%
58%
17%
Improved
Worsened
No Change
Fibrosis Stage at Baseline
Patients, % (n = 19)
16%
26%
53%
5%
F1
F2
F3
F4
Fibrosis Response at Wk 12
Patients, %
42%
47%
11%
ImprovedWorsened
No Change
38. NGM282: Safety
All Adverse Events
No new safety signals observed;
most events were mild or resolved
on treatment
Gastrointestinal Events
Most common treatment-emergent
adverse event was mild
gastrointestinal symptoms consisting
of nausea and loose, frequent stools
2 patients discontinued due to
diarrhea
Gastrointestinal symptoms improved
by separating dosing from mealtimes
and reducing meal size
Harrison. AASLD 2018. Abstr 104. Slide credit: clinicaloptions.com
Patients, n
NGM282
1 mg
NGM282
3mg
Serious adverse events
• Treatment related
1*
0
4†
0
*Renal mass.
†Cardiac arrest (nonmyocardial infarction), chest
pain (musculoskeletal), pleurisy, pneumonia.
43. MGL-3196 in Patients With NASH
Multicenter, randomized, double-blind, placebo-controlled phase II trial
‒ MGL-3196: THR-β agonist
*20-mg dose adjustment up or down
allowed at Wk 4.
Patients with biopsy-confirmed
NASH, NAS ≥ 4, F1-3 fibrosis, ≥ 10%
liver fat by MRI-PDFF
(N = 125)
MGL-3196 80 mg PO QD*
(n = 84)
Placebo PO QD
(n = 41)
Wk 36
Primary Endpoint
Wk 12
Harrison. AASLD 2018. Abstr 14. Slide credit: clinicaloptions.com
Open-label
extension study
44. MGL-3196: Efficacy at Wks 12, 36
Ongoing open-label extension suggests improvements of change in liver fat content are maintained
Harrison. AASLD 2018. Abstr 14. Slide credit: clinicaloptions.com
*P < .0001 vs placebo.
Reduction in Fibrosis Score ≥ 1 Point, % Placebo MGL-3196 P Value
Second harmonic generation score 12 32 .03
Pathology score 23 29 NS
MGL-3196*
Change in Liver Fat Content, %
Placebo
(n = 38)
All Patients
(n = 78)
High Exposure
(n = 44)
Wk 12 Wk 36 Wk 12 Wk 36 Wk 12 Wk 36
Relative -10 -8 -36 -37 -42 -49
Absolute -1.6 -2.3 -7.6 -8.5 -8.8 -9.4
≥ 30% relative reduction 18 30 60 68 75 77
Liver Fat Content by MRI-PDFF
Fibrosis at Wk 36
45. MGL-3196: Efficacy at Wks 12, 36
Ongoing open-label extension suggests improvements of change in liver fat content are maintained
Harrison. AASLD 2018. Abstr 14. Slide credit: clinicaloptions.com
*P < .0001 vs placebo.
Change in Fibrosis or NASH by Biopsy, % Placebo MGL-3196 P Value
Reduction in Fibrosis Score ≥ 1 Point
Second harmonic generation score
Pathology score
12
23
32
29
.03
NS
Resolution of NASH 6 27 .02
MGL-3196*
Change in Liver Fat Content by
MRI-PDFF, %
Placebo
(n = 38)
All Patients
(n = 78)
High Exposure
(n = 44)
Wk 12 Wk 36 Wk 12 Wk 36 Wk 12 Wk 36
Relative -10 -8 -36 -37 -42 -49
Absolute -1.6 -2.3 -7.6 -8.5 -8.8 -9.4
≥ 30% relative reduction 18 30 60 68 75 77
46. MGL-3196: Lipids, Safety
Lipids Safety
AEs generally mild and balanced
between groups, except increase in
loose stools at beginning of
treatment, usually 1 episode
‒ Some AEs moderate
Laboratory abnormalities balanced
between groups
Serious AEs (n = 7) balanced between
groups with none related to
treatment
Harrison. AASLD 2018. Abstr 14. Slide credit: clinicaloptions.com
Change in Lipids
From BL to Wk 36 % Change P Value
LDL-C -22.3 < .0001
ApoB -21.9 < .0001
Triglycerides -36 < .0001
Lp(a) -36.8 < .001
ApoCIII -36.5 < .0001
52. Semaglutide in Obese Patients With No Diabetes
Post hoc analysis of multicenter, randomized, double-blind phase II trial
Newsome. AASLD 2018. Abstr 105. Slide credit: clinicaloptions.com
Adults with BMI ≥ 30,
≥ 1 unsuccessful attempt at
weight loss, no diabetes
(N = 957)
Semaglutide .05 mg QD escalated Q4W* (n = 103)
Wk 52
Semaglutide .1 mg QD escalated Q4W* (n = 102)
Semaglutide .2 mg QD escalated Q4W* (n = 103)
Semaglutide .3 mg QD escalated Q4W* (n = 103)
Semaglutide .4 mg QD escalated Q4W* (n = 102)
Placebo* (n = 136)
Current
post hoc analysis
*Plus diet of -500 kcal/day and increased physical activity.
Semaglutide .3 mg QD escalated Q2W* (n = 102)
Semaglutide .4 mg QD escalated Q2W* (n = 103)
Liraglutide 3 mg QD escalated QW* (n = 103)
53. Semaglutide in Obese Patients With No Diabetes:
Baseline Characteristics
Newsome. AASLD 2018. Abstr 105. Slide credit: clinicaloptions.com
BL Characteristic
With Elevated BL ALT
(n = 499)
Without Elevated BL ALT
(n = 458)
Age, yrs (range) 48 (18-76) 47 (19-86)
Male, n (%) 187 (37.5) 151 (33.0)
Weight, kg (range) 106.9 (70.5-216.3) 107.8 (70.2-243.7)
BMI (range) 37.4 (29.7-77.1) 37.9 (29.7-80.3)
A1C, % (range) 5.5 (4.3-6.6) 5.5 (4.2-7.0)
Lipids, mmol/L (range)
Total cholesterol
LDL cholesterol
HDL cholesterol
Triglycerides
5.2 (2.7-9.7)
3.2 (1.1-6.2)
1.2 (0.5-2.4)
1.6 (0.5-11.9)
5.0 (2.6-10.3)
3.0 (0.8-7.2)
1.3 (0.7-2.9)
1.4 (0.4-9.9)
Liver enzymes, IU/L (range)
ALT
AST
34 (20-313)
24 (12-272)
17 (3-30)
16 (8-62)
Impaired fasting glucose (≥ 6.1 mmol/L), n/N (%) 76/499 (15.2) 57/457 (12.5)
*Elevated ALT defined as > 30 IU/L for men, > 19 IU/L for women.
54. Semaglutide in Obese Patients With Elevated ALT and
No Diabetes: Change in ALT Through 52 Wks
Newsome. AASLD 2018. Abstr 105. Slide credit: clinicaloptions.com
MeanALTRatiotoBaseline
Semaglutide 0.05 mg
Semaglutide 0.1 mg
Semaglutide 0.2 mg
Semaglutide 0.3 mg
Semaglutide 0.4 mg
Placebo
Wk 4 Wk 16 Wk 28 Wk 40 Wk 52
0.7
0.8
0.9
1.0
1.1
1.2
55. clinicaloptions.com/hepatitis
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