This document summarizes data presented at the 2018 International Liver Congress on noninvasive screening and clinical outcomes in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). New algorithms using blood tests and imaging were shown to improve detection of NASH and fibrosis without liver biopsy. Studies found patients with NAFLD/NASH and cirrhosis had high mortality, healthcare costs that increased substantially after cirrhosis diagnosis, and a significant economic burden on healthcare systems.
Clinical Impact of New NAFLD/NASH Data From San Francisco 2018hivlifeinfo
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
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
Clinical Impact of New NAFLD/NASH Data From San Francisco 2018hivlifeinfo
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
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
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
Management of Acute Variceal Bleeding based on American Association for The Study of Liver Disease (AASLD) and European Association for The Study of Liver (EASL) guidelines.
Join Dr. O’Dwyer for an exciting webinar on the National Cancer Institute-MolecularAnalysis for Therapy Choice trial, (NCI-MATCH or EAY131) This phase II precision medicine trial is currently available at more than 1000 locations around the United States, allowing many patients to enroll at a facility close to home
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
Management of Acute Variceal Bleeding based on American Association for The Study of Liver Disease (AASLD) and European Association for The Study of Liver (EASL) guidelines.
Join Dr. O’Dwyer for an exciting webinar on the National Cancer Institute-MolecularAnalysis for Therapy Choice trial, (NCI-MATCH or EAY131) This phase II precision medicine trial is currently available at more than 1000 locations around the United States, allowing many patients to enroll at a facility close to home
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...JohnJulie1
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group.
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...daranisaha
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...EditorSara
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group.
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...semualkaira
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...semualkaira
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group.
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...EditorSara
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group.
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...semualkaira
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline
tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous
group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant
treatment in this particular group.
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...semualkaira
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group.
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...NainaAnon
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group.
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...semualkaira
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline
tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous
group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant
treatment in this particular group.
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...EditorSara
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group.
Predictive Value of Biomarkers Fibrinogen Like Protein-2 and A-Fetoprotein fo...daranisaha
Data concerning the utility of biomarkers for accurate early HCC detection in cirrhotic patients are lacking. 1.2. Methods: We evaluated 112 consecutive Caucasian cirrhotic patients with (n=28) or without (n=84) concomitant HCC at baseline for serum AFP and plasma fibrinogen like protein-2 (FGL-2) levels. Patients without confirmed HCC at baseline were further followed up every six months with ultrasound and serum AFP levels, according to HCC surveillance program. Imaging as well as histological confirmation of HCC was established in patients with new lesion
Predictive Value of Biomarkers Fibrinogen Like Protein-2 and A-Fetoprotein fo...semualkaira
Data concerning the utility of biomarkers for accurate early HCC detection in cirrhotic patients are lacking. 1.2. Methods: We evaluated 112 consecutive Caucasian cirrhotic patients with (n=28) or without (n=84) concomitant HCC at baseline for serum AFP and plasma fibrinogen like protein-2 (FGL-2) levels. Patients without confirmed HCC at baseline were further followed up every six months with ultrasound and serum AFP levels, according to HCC surveillance program. Imaging as well as histological confirmation of HCC was established in patients with new lesions. Du
Predictive Value of Biomarkers Fibrinogen Like Protein-2 and A-Fetoprotein fo...semualkaira
Data concerning the utility of biomarkers for accurate early HCC detection in cirrhotic patients are lacking. 1.2. Methods: We evaluated 112 consecutive Caucasian cirrhotic patients with (n=28) or without (n=84) concomitant HCC at baseline for serum AFP and plasma fibrinogen like protein-2 (FGL-2) levels. Patients without confirmed HCC at baseline were further followed up every six months with ultrasound and serum AFP levels, according to HCC surveillance program. Imaging as well as histological confirmation of HCC was established in patients with new lesions. Du
Predictive Value of Biomarkers Fibrinogen Like Protein-2 and A-Fetoprotein fo...semualkaira
We evaluated 112 consecutive Caucasian cirrhotic
patients with (n=28) or without (n=84) concomitant HCC at baseline for serum AFP and plasma fibrinogen like protein-2 (FGL-2)
levels. Patients without confirmed HCC at baseline were further
followed up every six months with ultrasound and serum AFP levels, according to HCC surveillance program. Imaging as well as
histological confirmation of HCC was established in patients with
new lesions. During 5-year surveillance, 14 (16.6%) patients developed HCC
Similar to Clinical Impact of New NAFLD/NASH Data From EASL 2018 (20)
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.
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
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
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!
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
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Clinical Impact of New NAFLD/NASH Data From EASL 2018
1. Clinical Impact of New NAFLD/NASH Data From
EASL 2018
*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.
This program is supported by educational grants from AbbVie and Gilead Sciences
CCO Independent Conference Coverage*
of the 2018 International Liver Congress, April 11-15, 2018
2. About These Slides
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Slide credit: clinicaloptions.com
3. Faculty
Vlad Ratziu, MD, PhD
Professor of Hepatology
University Pierre et Marie Curie Hospital La Pitié-Salpêtrière
Paris, France
Zobair M. Younossi, MD, MPH, FACP, FACG, AGAF, FAASLD
Chairman, Department of Medicine
Professor of Medicine
Inova Fairfax Hospital
Inova Health System
Falls Church, Virginia
4. Disclosures
Vlad Ratziu, MD, PhD, has disclosed that he has received
consulting fees from Allergan, Boehringer Ingelheim, Genfit,
Intercept, Novartis, and Novo-Nordisk and funds for research
support from Gilead Sciences and Intercept Pharmaceuticals.
Zobair M. Younossi, MD, MPH, FACP, FACG, AGAF, FAASLD,
has disclosed that he has received consulting fees or funds for
research support from Allergan, Bristol-Myers Squibb, Gilead
Sciences, Intercept, Novartis, NovoNordisk, and Shinogi.
5. Outline
Noninvasive Screening for NAFLD/NASH
Clinical Outcomes in Patients With NAFLD/NASH
Treatment of NAFLD/NASH
Slide credit: clinicaloptions.com
7. Detection of NASH in Patients With T2DM
Prospective, multicenter UK study
of patients undergoing liver biopsy
for possible NAFLD (N = 408)
– Noninvasive algorithm developed
in subset of evaluable patients with
NAFLD and T2DM
Algorithm based on ALT, CAP, and
elastometry values measured by
FibroScan
Goals for algorithm
– To identify NASH with activity > 2
– Activity (SAF score) based on sum
of ballooning (graded 0-2) and
lobular inflammation (graded 0-2)
– To improve SFR by > 30%
– To keep missed cases < 15%
Eddowes P, et al. EASL 2018. Abstract FRI-424. Slide credit: clinicaloptions.com
Patient Characteristic T2DM (n = 176)
Median age, yrs (IQR) 58 (14)
Female, n (%) 86 (49)
Median BMI (IQR) 34.4 (8.7)
NASH, n (%) 135 (77)
NASH with activity > 2, n (%) 90 (51)
8. Algorithm Improves Noninvasive Detection of
NASH With Activity > 2 in Patients With T2DM
SFR improved by 35%, missed cases < 15%, 36% of patients
could have avoided liver biopsy with this algorithm
Eddowes P, et al. EASL 2018. Abstract FRI-424. Slide credit: clinicaloptions.com
All T2DM
Patients
N = 176
NA > 2 = 90
SFR = 49%
MCR = 0%
SIR = 0%
Step 1
ALT/ULN ≥ 0.71
N = 135
NA > 2 = 85
SFR = 37%
MCR = 6%
SIR = -23%
Step 2
CAP ≥ 270 dB/m
N = 123
NA > 2 = 81
SFR = 34%
MCR = 10%
SIR = -30%
Step 3
E ≥ 6.1 kPa
N = 113
NA > 2 = 77
SFR = 32%
MCR = 14%
SIR = -36%
9. Multiparametric MRI Identifies, Stratifies
NAFLD/NASH
Utility of multiparametric MRI to
identify and stratify NAFLD/NASH
assessed in 2 large cohorts
– In all patients, LiverMultiScan™
protocol estimated PDFF and cT1
– UK Biobank cohort: ongoing national
study to collect imaging data from
100,000 individuals (n = 2895)
– US San Antonio cohort: patients with
no prior liver disease or alcohol abuse
undergoing routine colon cancer
screen (n = 477)
– Offered biopsy if FibroScan ≥ 7 kPa,
MRE ≥ 3 kPa, PDFF ≥ 5%, or LIF ≥ 2
Of 139 biopsied US patients with
PDFF ≥ 5% and cT1 ≥ 800 ms:
– 98% had NAFLD, 67% had NASH,
and 29% had NASH with F2/3 fibrosis
– Addition of cT1 to PDFF enriched
NASH stratification 116% to 253%
Based on US biopsy analysis,12%
projected NASH prevalence in UK
cohort
– In UK subset with PDFF ≥ 5%, NASH
predicted at 49%; NASH with F2/3
fibrosis at 15%
Harrison S, et al. EASL 2018. Abstract FRI-421. Slide credit: clinicaloptions.com
10. Hepamet Score Improves Noninvasive
Classification of Fibrosis in Patients With NAFLD
Noninvasive panel to predict fibrosis
stage developed in patients with
biopsy-proven NAFLD
– Spain, n = 758; France, n = 444; Cuba,
n = 344; Italy, n = 288
– 36% significant fibrosis, 20% advanced
fibrosis, 6% cirrhosis
– Estimation in Spanish cohort,
validation in remaining patients
Variables associated with advanced
fibrosis: older age, female sex, T2DM,
HOMA ≥ 4, AST ≥ 35 IU/mL, albumin
< 4 g/dL, and PLT ≤ 220 x 109
Compared with FIB-4 and NFS,
Hepamet Fibrosis Score:
– Improved classification of fibrosis in
patients with NAFLD
– Reduced proportion of patients falling
in the grey zone
– Avoided age-adjusted cutoffs
Ampuero J, et al. EASL 2018. Abstract PS-179. Slide credit: clinicaloptions.com
AUROC
(N = 1834)
Hepamet NFS FIB-4
P
Value
F2-F4 0.758 0.679 0.731 .0001
F3-F4 0.847 0.767 0.797 .0001
F4 0.902 0.863 0.875 .0397
11. Pooled Analysis of MRE vs TE to Detect Fibrosis
in Patients With NAFLD
Systematic review and meta-analysis of pooled patient data from
studies comparing MRE vs TE for fibrosis staging in NAFLD[1]
Study eligibility:
– MRE and TE used to assess liver stiffness
– Liver biopsy used as reference
– Fibrosis staging system comparable to biopsy staging
– Included adult patients with NAFLD
3 studies met criteria for inclusion[2-4]
1. Hsu C, et al. EASL 2018. Abstract FRI-439. 2. Chen J, et al. Radiology. 2017;283:418-428.
3. Imajo K, et al. Gastroenterology. 2016;150:626-637.e7. 4. Park CC, et al. Gastroenterology.
2017;152:598-607.e2. Slide credit: clinicaloptions.com
12. Overall
(n = 230)
AUROC
Optimal
Threshold,
kPa
Sensitivity,
%
Specificity,
%
PPV, % NPV, %
P
Value
Stage 1-4 (n = 157) vs 0 (n = 73)
MRE
TE
0.8685
0.8184
2.61
6.2
71.3
65.6
72.6
67.1
84.9
81.1
54.1
47.6
.0394
Stage 2-4 (n = 93) vs 0-1 (n = 137)
MRE
TE
0.9193
0.8664
2.97
7.6
84.9
76.3
85.4
79.6
79.8
71.7
89.3
83.2
.0265
Stage 3-4 (n = 57) vs 0-2 (n = 173)
MRE
TE
0.9295
0.8411
3.62
8.8
82.5
77.2
83.2
78.0
61.8
53.7
93.5
91.2
.0004
Stage 4 (n = 25) vs 0-3 (n = 205)
MRE
TE
0.9423
0.8357
4.7
11.8
80.0
80.0
85.9
81.0
40.8
33.9
97.2
97.1
.0046
Significantly Higher Diagnostic Accuracy With
MRE vs TE for Fibrosis Staging in NAFLD
Hsu C, et al. EASL 2018. Abstract FRI-439. Slide credit: clinicaloptions.com
13. Serum biomarkers (eg, THBS2,
COLEC11) validated by ELISA
Comparison
L1OXV
Accuracy, %
NASH vs simple steatosis
5-protein NASH
predictor panel
91.7
NASH F0-2 vs F3-4
43-protein principal
component analysis
6-protein fibrosis
predictor panel
95
97.5
SOMAscan: Serum Biomarker Analysis to
Distinguish Simple Steatosis From NASH
Multiplexed proteomics tool used to
examine serum biomarkers
– Simple steatosis, n = 20
– NASH with F0-2 fibrosis, n = 20
– NASH with F3-4 fibrosis, n = 20
Objectives:
– Develop simple noninvasive
screening test to differentiate
between NASH and simple
steatosis, and fibrosis stages
– Identify new therapeutic targets
Lai M, et al. EASL 2018. Abstract PS-181. Slide credit: clinicaloptions.com
14. Hierarchical clustering of 45
statistically significant proteins
discriminates NASH vs simple
steatosis
SOMAscan: Clear Biomarker Profiles Identify
NASH vs Simple Steatosis
Hierarchical clustering of 20
statistically significant proteins
discriminates NASH F0-2 vs
simple steatosis
Lai M, et al. EASL 2018. Abstract PS-181. Reproduced with permission. Slide credit: clinicaloptions.com
Upregulated
Downregulated
NASH
Simple
Steatosis
NASH F0-2
Simple
Steatosis
16. Economic and Disease Burden of NAFLD/NASH
in German Claims Database
Retrospective cohort study of anonymized healthcare claims from
German InGef research database (N = 4,580,434)
– Mortality, comorbidities, resource utilization, and healthcare costs
examined in subset of 800 adults diagnosed with NAFLD/NASH
and compensated cirrhosis
Canbay A, et al. EASL 2018. Abstract PS-057. Slide credit: clinicaloptions.com
Characteristic
NAFLD/NASH + CC
(n = 800)
Progressors*
(n = 245)
Nonprogressors†
(n = 555)
Mean age, yrs (SD) 67.8 (12.4) 72.0 (11.1) 66.1 (12.5)
Male, % 58 60 57
*Did or †did not progress to ESLD (ie, decompensated cirrhosis, HCC, or liver transplant) within 1 yr of CC diagnosis.
17. High Mortality and Comorbidity Burden in
German NAFLD/NASH Patients With Cirrhosis
19.4% of patients died in first yr after cirrhosis diagnosis
– Rate significantly higher in progressors vs nonprogressors
(46.1% vs 7.6%, respectively; P < .0001)
Canbay A, et al. EASL 2018. Abstract PS-057. Canbay A, et al. EASL 2018. Abstract SAT-252. Slide credit: clinicaloptions.com
Comorbidity in Yr
Preceding CC, %
NAFLD/NASH + CC
(n = 800)
Progressors
(n = 245)
Nonprogressors
(n = 555)
CVD 49 57 45
Renal impairment 32 39 29
Obesity 37 40 36
Hypertension 79 84 77
Hyperlipidemia 48 47 48
18. Healthcare Costs Spike Following Cirrhosis
Diagnosis in Patients With NAFLD/NASH
Mean annual all-cause healthcare costs increased 93% by 1 yr post CC
– Primarily driven by a 214% increase in inpatient costs; elevations significantly
more pronounced in progressors vs nonprogressors
Mean cumulative all-cause total healthcare costs also significantly increased
– At 5 yrs post CC, 169% for progressors vs 132% for nonprogressors
Canbay A, et al. EASL 2018. Abstract PS-057. Canbay A, et al. EASL 2018. Abstract SAT-252. Slide credit: clinicaloptions.com
Annual Healthcare
Resource Utilization
NAFLD/NASH + CC
(n = 800)
Progressors
(n = 245)
Nonprogressors
(n = 555)
Pre CC Post CC Pre CC Post CC Pre CC Post CC
Mean hospitalizations, n 0.8 1.5 1.0 2.4 0.7 1.1
Mean length of stay, days 8.8 14.8 12.2 25.8 7.4 10.0
Mean ED visits, n 3.5 7.3 5.7 13.3 2.6 4.7
19. Economic and Disease Burden of NAFLD/NASH
in US Medicare Claims Database
Retrospective, observational cohort study of 20% sample of US
Medicare patients from 2007-2015 (N = 10,826,456)
– Comorbidities and healthcare costs examined in subset of
3775 adults with NAFLD/NASH and compensated cirrhosis
– Follow-up: CC index to death, end of Medicare coverage, end of
2015, or 5 yrs post index
Loomba R, et al. EASL 2018. Abstract SAT-251. Slide credit: clinicaloptions.com
Characteristic
NAFLD/NASH + CC
(n = 3775)
Progressors*
(n = 1048)
Nonprogressors†
(n = 2727)
Mean age, yrs (SD) 66.95 (10.90) 68.01 (10.70) 66.55 (10.90)
Male, % 37 35 37
*Did or †did not progress to ESLD (ie, decompensated cirrhosis, HCC, or liver transplant) during study period.
20. Comorbidity, %
NAFLD/NASH + CC
(n = 3775)
Progressors
(n = 1048)
Nonprogressors
(n = 2727)
7-Yr Cost Increase*
Diabetes 75 79 73 47
Hyperlipidemia 92 93 91 37
Hypertension 94 96 93 104
CVD 84 93 81 128
High Metabolic Comorbidity, Cost Burden in US
NAFLD/NASH Patients With Cirrhosis
High burden of metabolic comorbidity in
US NAFLD/NASH patients with CC
– Numerically higher but similar levels in
progressors vs nonprogressors
Mean annual healthcare costs significantly
greater in progressors vs nonprogressors,
P < .0001
7-yr cumulative healthcare costs highest
in comorbid patients, progressors to
ESLD
– Overall: 891%
– Progressors: 1120%
– Nonprogressors: 698%
Loomba R, et al. EASL 2018. Abstract SAT-251. Slide credit: clinicaloptions.com
*Cumulative healthcare costs in those with vs without comorbidity (ie, 2 yrs prior to CC index to 5 yrs postindex).
21. Incidence of Serious Liver Disease in European
Patients With NAFLD/NASH
Analysis of cirrhosis, HCC
incidence in patients with
NAFLD/NASH from 4 European
primary care databases (UK,
Netherlands, Italy, Spain; N =
145,590)
– Registration from 2004 to 2015;
median follow-up: 3.3 yrs
– Exclusion criteria: follow-up
< 1 yr, age/sex missing,
previous cirrhosis, HCC, or
alcohol abuse
Alexander M, et al. EASL 2018. Abstract PS-106. Slide credit: clinicaloptions.com
Parameter
NAFLD/
NASH
Matched
Controls*
Mean age, yrs 55.8 54.6
Male, % 52.7 50.1
Current smoker, % 16.5 14.4
Mean BMI 31.3 28.5
Obesity, % 36.0 15.4
T2DM, % 19.8 9.6
Hypertension, % 42.2 29.6
Mean AST, U/mL 28 21
Mean ALT, U/mL 35 21
*For each NAFLD/NASH patient, up to 100 non-NAFLD/NASH
patients matched by site, sex, age at index date ± 5 yrs, visit
date at index date ± 6 mos.
22. Associations Between NAFLD/NASH and
Cirrhosis or HCC
Like NAFLD/NASH, diabetes also independently predicted
cirrhosis or HCC outcome (HR: 2.66; 95% CI: 2.52-2.81)
Alexander M, et al. EASL 2018. Abstract PS-106. Reproduced with permission. Slide credit: clinicaloptions.com
Cirrhosis
*UK/Spain only.
†Adjusted for age, smoking, BMI.
NAFLD/NASH
NAFLD*
NASH*
4.73 (2.43-9.19)
5.83 (1.87-18.13)
22.67 (5.96-86.23)
HR (95% CI)†
HCC
NAFLD/NASH
NAFLD*
NASH*
3.51 (1.72-7.16)
3.15 (1.16-8.56)
8.02 (4.08-15.77)
HR (95% CI)†
0.6 1 2 4 6 16 32 64128252 0.1 0.6 1 2 4 8 16 32 641280.3 252
23. Progression to NASH, Cirrhosis Variable by
Geographic Region
Likelihood of progression from NAFLD to NASH significantly
higher in UK vs Spain
– Regional variations suggest underdiagnosis in UK settings
Alexander M, et al. EASL 2018. Abstract PS-106. Slide credit: clinicaloptions.com
Progression to
Cirrhosis
Incidence/
1000 PY
Median
Time, Yrs
From NAFLD
Spain
UK
0.66
2.17
3.0
2.0
From NASH
Spain
UK
2.8
5.8
3.0
0.5
Progression to NASH HR (95% CI)
Unadjusted
Spain
UK
0.03 (0.01-0.05)
1.29 (1.06-1.57)
Adjusted for age, smoking
Spain
UK
3.14 (1.47-6.72)
25.13 (20.12-31.38)
24. HCHS/SOL: Alcohol Use and NAFLD in
Hispanics/Latinos Living in the US
Longitudinal, population-based
cohort of Hispanic/Latino adults
living in the US (N = 16,415)
– BL data collected 2008-2011
Relationship between alcohol use
and NAFLD assessed
– Analyzed in subset of individuals
with no HBV or HCV infection, iron
overload, or heavy alcohol use
(> 14 drinks/wk for women,
> 21 drinks/wk for men)
Unalp-Arida A, et al. EASL 2018. Abstract SAT-514. Slide credit: clinicaloptions.com
Weighted Prevalence, %
Analyzed
(n = 14,786)
Alcohol use
Never
Former
Occasional*
Low to moderate†
19.6
30.7
16.6
33.2
NAFLD and liver fibrosis
No NAFLD
NAFLD without fibrosis
NAFLD with fibrosis
Undetermined fibrosis status
82.8
15.3
1.6
0.3
Drinks/wk: *< 1, †1-14 for women, 1-21 for men.
25. Association Between Alcohol Use and NAFLD
in US Hispanics/Latinos
In age-adjusted model
– NAFLD prevalence lower in occasional, low to moderate vs never, former
alcohol users (P < .05)
In multivariable-adjusted model
– NAFLD odds reduced ~ 30% in occasional and low to moderate, 20% in
former vs never alcohol users
– Stronger association between low to moderate, former drinking and
NAFLD in those with vs without fibrosis
– No association between alcohol use category and NAFLD after further
adjustment for insulin resistance
Unalp-Arida A, et al. EASL 2018. Abstract SAT-514. Slide credit: clinicaloptions.com
27. Agents in Phase III Clinical Trials for Treatment of
NASH
Slide credit: clinicaloptions.comReferences in slidenotes.
Agent MoA Trial N Study Population
Cenicriviroc CCR2/5 antagonist AURORA[1] 2000 NASH with fibrosis
Elafibranor PPARα/σ agonist RESOLVE-IT[2] 2000 NASH with fibrosis
Obeticholic acid FXR agonist
REGENERATE[3] 2370 NASH with fibrosis
REVERSE[4] 540 NASH with compensated cirrhosis
Selonsertib ASK1 inhibitor
STELLAR 3[5] 800 NASH with fibrosis
STELLAR 4[6] 883 NASH with compensated cirrhosis
28. Phase II Data on Investigational NASH Therapies
Presented at EASL 2018
Slide credit: clinicaloptions.com
Agent Mechanism of Action
Cenicriviroc[1,2] CCR2/5 antagonist
GR-MD-02[3,4] Galectin-3 inhibitor
GS-0976*[5-7] ACC inhibitor
(GS-0976 or GS-9674) ± selonsertib[8,9] (ACC inhibitor or FXR agonist) ± ASK1 inhibitor
JKB-121[10,11] TLR-4 antagonist
MGL-3196[12,13] THR-β agonist
NGM282*[14] FGF19 analogue
Semaglutide†[15,16] GLP-1 receptor agonist
References in slidenotes.
*Includes single-arm exploratory or proof-of-concept studies; all others phase II.
†FDA approved as adjunct to diet and exercise to improve glycemic control in adults with T2DM.
29. CENTAUR: Final Analysis of Cenicriviroc vs
Placebo in Patients With NASH
International, randomized, double-blind, placebo-controlled phase IIb study[1]
– Cenicriviroc: CCR2/5 antagonist
Primary analysis at Yr 1 observed significant improvement in fibrosis stage with no
worsening of NASH with use of cenicriviroc vs placebo[2]
1. Ratziu V, et al. EASL 2018. Abstract GS-002. 2. Friedman SL, et al. Hepatology. 2018;67:1754-1767. Slide credit: clinicaloptions.com
Cenicriviroc 150 mg PO QD
(n = 145)
Placebo PO QD
(n = 72)
Stratified by NAS (4 vs ≥ 5),
fibrosis stage (≤ vs > 2)
Yr 1
Primary Endpoint
Yr 2
Final Analysis
Placebo PO QD
(n = 72)
Cenicriviroc 150 mg PO QD
(n = 61)
Placebo PO QD
(n = 60)
Patients underwent 3 serial liver biopsies during 2-yr study: BL, Yr 1, Yr 2.
Arm A
Cenicriviroc 150 mg PO QD
(n = 121)
Patients with NASH,
NAS ≥ 4, and
F1-3 fibrosis
(N = 289)
Arm B
Arm C
30. CENTAUR: Continued Antifibrotic Activity in Yr 1
Responders Twice as Frequent With Cenicriviroc
Ratziu V, et al. EASL 2018. Abstract GS-002. Reproduced with permission. Slide credit: clinicaloptions.com
11%
Pooled analysis of all
patients receiving 1 yr
of CVC supports
primary findings
Use of CVC
associated with
reduction in hs-CRP
and fibrinogen at Yr 2
vs apparent increase
with PBOWorsened from BL
Maintained ≥ 1-stage improvement in fibrosis
No change from BL
Antifibrotic Activity in
Previous Responders*
Yr 1 to Yr 2
100
80
60
40
20
0
Patients(%)
Arm A: CVC
(n = 30)
Arm C: PBO
(n = 10)
*Subset achieving ≥ 1-stage improvement in fibrosis at Yr 1.
60%
30%
Improvement in Fibrosis by ≥ 2
Stages and no Worsening of NASH
BL to Yr 2
Patients(%)
Arm A: CVC
(n = 65)
Arm C: PBO
(n = 34)
14
8
6
4
2
0
10
12
P = .13
3%
31. Safety Outcome, n (%)
Arm A: CVC
(n = 121)
Arm B: PBO/CVC
(n = 61)
Arm C: PBO
(n = 60)
TEAEs
By maximum severity
• Grade 1
• Grade 2
• Grade 3
• Grade 4
Leading to discontinuation
Study drug-related
105 (86.8)
40 (33.1)
47 (38.8)
17 (14.0)
1 (0.8)
19 (15.7)
5 (4.1)
46 (75.4)
25 (41.0)
17 (27.9)
4 (6.6)
0
6 (9.8)
0
50 (83.3)
22 (36.7)
19 (31.7)
8 (13.3)
1 (1.7)
9 (15.0)
0
Grade ≥ 2 study drug-related
TEAEs occurring in ≥ 2% patients
ALT elevation
10 (8.3)
3 (2.5)
0
0
3 (5.0)
2 (3.3)
Treatment-emergent SAEs
Leading to discontinuation
13 (10.7)
1 (0.8)
3 (4.9)
0
9 (15.0)
0
CENTAUR: Cenicriviroc Well Tolerated in Yr 2
No deaths or study drug-related, treatment-emergent SAEs
Ratziu V, et al. EASL 2018. Abstract GS-002. Slide credit: clinicaloptions.com
32. NASH-CX: GR-MD-02 vs Placebo in Patients With
NASH Cirrhosis and Portal Hypertension
Multicenter, randomized, double-blind, placebo-controlled phase II trial
– GR-MD-02: galectin-3 inhibitor
Primary endpoint: change in HVPG at Wk 54
Chalasani N, et al. EASL 2018. Abstract LBO-001. ClinicalTrials.gov. NCT02462967. Slide credit: clinicaloptions.com
Patients with NASH cirrhosis
on biopsy, HVPG ≥ 6 mm Hg,
no decompensating event, and
no or small varices
(N = 161)
GR-MD-02 8 mg/kg
(n = 54)
GR-MD-02 2 mg/kg
(n = 53)
Wk 54
Placebo
(n = 54)
Treatment administered every other week by IV infusion x 26.
33. NASH-CX: GR-MD-02 Significantly Reduced
HVPG at Wk 54 in Subset With Mild Portal HTN
GR-MD-02 use improved hepatocyte ballooning
In patients with no varices at BL, GR-MD-02 2 mg/kg associated with significant difference in change
in HVPG, percentage of responders, development of new varices
Chalasani N, et al. EASL 2018. Abstract LBO-001. Reproduced with permission. Slide credit: clinicaloptions.com
Total Patient Population Patients With Mild Portal Hypertension*
MeanChangeinHVPGFrom
BLtoWk54±SEM(%)
MeanChangeinHVPGFrom
BLtoWk54±SEM(%)
15
10
5
0
-5
GR-MD-02
8 mg/kg
GR-MD-02
2 mg/kg
Placebo
n = 53n = 54
-2%-2%
P = .10
n = 54
8%
P = .10
40
30
20
0
-10
GR-MD-02
8 mg/kg
GR-MD-02
2 mg/kg
Placebo
n = 16n = 16
-3%
-2%
P = .027
n = 21
26%
P = .021
10
-20
*Prespecified analysis in subset with ≥ 6 and < 10 mm Hg.
34. NASH-CX: GR-MD-02 Well Tolerated at Wk 54
Chalasani N, et al. EASL 2018. Abstract LBO-001. Slide credit: clinicaloptions.com
Safety Outcome
All Patients
(N = 161)
GR-MD-02
8 mg/kg
(n = 54)
GR-MD-02
2 mg/kg
(n = 53)
Placebo
(n = 54)
TEAEs, n 1323 383 509 431
Grade ≥ 3 AE, n (%) 33 (20.5) 11 (20.4) 11 (20.8) 11 (20.4)
≥ 1 treatment-
emergent SAE, n
(total)
25 (34) 12 (14) 5 (10) 8 (10)
D/c for AE, n 3 3 0 0
Death, n 1 0 1 0
35. GS-0976 Reduces Liver Fat, ALT in Preliminary
Study of Patients With NASH Cirrhosis
Proof-of-concept study to examine
pharmacodynamics, efficacy, and
safety of 12-wk GS-0976 20 mg
PO QD in patients with Child-Pugh
A cirrhosis due to NASH (N = 10)
≥ 30% MRI-PDFF reduction at Wk
12 in 70% of patients
MRE stiffness unchanged from BL
to Wk 12
Significant increase in median
fasting triglycerides: 147 mg/dL at
BL, 156 mg/dL at Wk 12; P = .004
Harrison S, et al. EASL 2018. Abstract FRI-487. Slide credit: clinicaloptions.com
Change From BL to
Wk 12, %
GS-0976
(N = 10)
P
Value
De novo lipogenesis -32 .01
Liver fat by MRI-PDFF -39 .004
ALT -29 .004
Safety Outcome, n
GS-0976
(N = 10)
TEAEs
Grade 3
8
1
Treatment-related AEs
Grade ≥ 2
4
2
TE grade 3 lab abnormalities 4
36. Wk 1
No Lasting Lipid Disturbance in Noncirrhotic
Patients With NASH Receiving GS-0976
Subanalysis of randomized, double-blind,
placebo-controlled phase II trial[1,2]
– GS-0976: ACC inhibitor
– 16% of GS-0976 recipients had grade 3/4 ↑ TG
at Wk 12 during primary analysis[3]
Current aim: to further characterize 12-wk lipid
changes with GS-0976 20 mg
TG and VLDL-TG significantly increased vs
placebo at Wk 1, with no differences by Wk 12
No significant changes in TC, LDL-C, LDL-P,
HDL-C, HDL-P, or VLDL-P following 12-wk
GS-0976 20 mg treatment
References in slidenotes Slide credit: clinicaloptions.com
Noncirrhotic
adults with
NASH
(N = 126)
GS-0976 20 mg PO QD
(n = 49)
GS-0976 5 mg PO QD
(n = 51)
Placebo PO QD
(n = 26)
Wk 12
*P < .05 vs BL. †P < .05 for change from BL vs placebo.
MedianΔ,mg/dL(IQR)
Changes in TG With GS-0976 20 mg Treatment
400
300
200
100
0
BL Wk 4 Wk 8 Wk 12
GS-0976 20 mg
Placebo
*
***
†
37. Selonsertib, GS-0976, and GS-9674—Alone or in
Combination—for Patients With NASH
Open-label, proof-of-concept phase II study
– Selonsertib: ASK1 inhibitor, GS-0976: ACC inhibitor, GS-9674: FXR agonist
Endpoints: change in liver fat by MRI-PDFF, liver stiffness by MRE; safety
Lawitz E, et al. EASL 2018. Abstract PS-105. ClinicalTrials.gov. NCT02781584. Slide credit: clinicaloptions.com
Patients with a clinical
diagnosis of NAFLD;
MRI-PDFF ≥ 10% and
MRE ≥ 2.88 kPa or biopsy
consistent with NASH and
F2/3 fibrosis; no cirrhosis
(N = 70)
Selonsertib 18 mg PO QD
(n = 10)
GS-0976 20 mg PO QD
(n = 10)
GS-9674 30 mg PO QD
(n = 10)
Selonsertib 18 mg + GS-0976 20 mg PO QD
(n = 20)
Selonsertib 18 mg + GS-9674 30 mg PO QD
(n = 20)
Wk 12
38. Combination Regimens Improved Liver Fat,
Biochemistry at Wk 12
Robust reductions in liver fat and ALT with
GS-0976 ± selonsertib
Reduction in ALT with GS-9674
monotherapy, in GGT with GS-9674 ±
selonsertib
Lawitz E, et al. EASL 2018. Abstract PS-105. Reproduced with permission. Slide credit: clinicaloptions.com
Median Relative
Change at Wk 12, %
SEL
(n = 10)
GS-0976
(n = 10)
GS-9674
(n = 10)
SEL + GS-0976
(n = 20)
SEL + GS-9674
(n = 20)
MRE-stiffness -8.6 (-15.6 to 13.6) -8.9 (-15.1 to -6.3) -8.3 (-14.7 to 6.7) -4.5 (-17.7 to 9.3) -5.2 (-15.3 to 13.8)
*P < .05 for Wk 12 vs BL.
MedianRelative
ChangeatWk12(%)
20
0
-20
-40
-60
MRI-PDFF ALT GGT
GS-9674
7.1 10.1
-42.7*
-15.6*
-32.0*
-9.4
-1.2
-33.5
-29.7 -27.2*
-3.0 -4.4
-1.6
-19.3*
-14.7*
SEL + GS-9674SEL + GS-0976GS-0976SEL
39. Combination Regimens Well Tolerated at Wk 12
All patients completed study treatment; no deaths observed
AEs occurring in > 1 patient included headache, diarrhea, acute sinusitis,
fatigue, constipation, cough, mood swings, and noncardiac chest pain
Lawitz E, et al. EASL 2018. Abstract PS-105. Slide credit: clinicaloptions.com
Safety Outcome, n (%)
SEL
(n = 10)
GS-0976
(n = 10)
GS-9674
(n = 10)
SEL +
GS-0976
(n = 20)
SEL +
GS-9674
(n = 20)
Any AE
Treatment-related
Grade 3/4
5 (50)
3 (30)
0
6 (60)
1 (10)
0
5 (50)
0
0
8 (40)
5 (25)
0
5 (25)
2 (10)
1 (5)
Serious AE 0 0 0 1 (5) 1 (5)
Grade 3/4 lab abnormality
TG > 500 mg/dL
2 (20)
0
2 (20)
1 (10)
4 (40)
0
4 (20)
2 (10)
2(10)
0
40. Followed
through
Wk 28
No Difference in Liver Fat Change by MRI-PDFF
for JKB-121 vs Placebo in Patients With NASH
Randomized, double-blind, placebo-
controlled phase IIa trial
– JKB-121: TLR-4 antagonist
Primary endpoints: safety, change in
liver fat by MRI-PDFF
At Wk 24, no difference for JKB-121
vs placebo in change of MRI-PDFF,
serum ALT, or body weight
– Significant improvement from BL in
MRI-PDFF and FIB4 with placebo
Diehl AM, et al. EASL 2018. Abstract LBO-006. Reproduced with permission. Slide credit: clinicaloptions.com
Adults with NASH;
F1-3 fibrosis in
last 12 mos; MRI-
PDFF ≥ 6%; ALT
increased at
screening and ≥
1x in last 12 mos;
A1C ≤ 9.0%; no
other chronic liver
disease
(N = 65)
JKB-121 10 mg PO BID
(n = 22)
JKB-121 5 mg PO BID
(n = 21)
Placebo PO BID
(n = 22)
Wk 24
ChangeinMRI-PDFF
atWk24(%)
5
10
-5
-10
-15
JKB-121 10 mg
(n = 11)
P = .28 vs BL
JKB-121 5 mg
(n = 17)
P = .04 vs BL
Placebo
(n = 19)
P < .01 vs BL
0
41. MGL-3196 vs Placebo in Patients With NASH
Multicenter, randomized, double-blind, placebo-controlled phase II trial
– MGL-3196: THR-β agonist
Primary endpoint: relative liver fat reduction by MRI-PDFF at Wk 12
Secondary endpoints: ≥ 30% relative reduction and absolute reduction in liver fat,
lipids, fibrosis and inflammatory biomarkers at Wk 12
Harrison S, et al. EASL 2018. Abstract GS-009. ClinicalTrials.gov. NCT02912260. Slide credit: clinicaloptions.com
Extension
study to Wk 48
*20-mg dose adjustment up or down allowed at Wk 4.
Patients with biopsy-confirmed
NASH, NAS ≥ 4, F1-3 fibrosis, ≥
10% liver fat on MRI-PDFF
(N = 125)
MGL-3196 80 mg PO QD*
(n = 84)
Placebo PO QD
(n = 41)
Wk 36
Primary Endpoint
Wk 12
42. MGL-3196 Significantly Reduced Liver Fat and
Markers of Inflammation at Wk 12
Compared with placebo at Wk 12,
MGL-3196 significantly reduced:
– Blood pressure (P = .002 for diastolic;
P = .005 for systolic)
– Atherogenic lipids (P < .0001 for LDL-C,
Lp(a), Apo B, and TG)
– Liver enzymes in patients with high MGL-
3196 exposure (P = .04 for ALT; P = .02
for AST)
– Fibrosis biomarkers in patients with BL
elevations (P = .002 for pro-C3; P = .009
for ELF)
2/9 (22%) discontinuations for AEs
At Wk 12, significant relative ↓ in MRI-
PDFF, ↑ in proportion with ≥ 30% fat
reduction with MGL-3196 vs placebo was
independent of NAS, fibrosis stage
Harrison S, et al. EASL 2018. Abstract GS-009. Slide credit: clinicaloptions.com
Efficacy Endpoint*
MGL-3196
(n = 78)
Placebo
(n = 38)
Relative Δ in MRI-PDFF, % -36.3 -9.6
Absolute Δ in MRI-PDFF -7.6 -2.4
≥ 30% fat reduction, % 60.3 18.4
*P < .0001 for each. †Study is blinded; 3 SAEs, none tx-related.
Safety Endpoint,† n (%)
MGL-3196
(n = 84)
Placebo
(n = 41)
Mild 55 (65.5) 19 (46.3)
Moderate 18 (21.4) 7 (17.1)
43. NGM282 in Patients With NASH
Exploratory single-center, single-arm study
– NGM282: FGF19 analogue
Primary endpoint: decrease in absolute liver fat ≥ 5% at Wk 12
Exploratory endpoint: change in liver histology at Wk 12
Harrison S, et al. EASL 2018. Abstract GS-014. Slide credit: clinicaloptions.com
Patients with biopsy-
confirmed NASH, NAS ≥ 4,*
stage 1-3 fibrosis, liver fat ≥
8% by MRI-PDFF
(N = 22)
NGM282 3 mg SC QD†
*≥ 1 point in each component. †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.
Wk 12
Followed
through Wk 18
44. NGM282 Reduced Liver Fat, Improved Histology
at Wk 12
Significant reductions in ALT, AST, pro-
C3, ELF, LIF, and cT1 at Wk 12
8/19 (42%) patients with BL F2/3 had ≥ 1
stage improvement in fibrosis at Wk 12
– Regression of fibrosis or no change in
89% of patients
Mild GI symptoms most common TEAE,
resolved during treatment
All patients exhibited ≥ 5% absolute and ≥
30% relative reduction in liver fat at Wk 12
– 12/19 (63%) patients with liver fat ≤ 5%
Harrison S, et al. EASL 2018. Abstract GS-014. Slide credit: clinicaloptions.com
*P < .0001
Mean Change in Liver
Fat at Wk 12, % (SD)
Evaluable Patients
(n = 19)
Absolute -11.2 (4.2)*
Relative -67 (17)
Histologic Response at Wk 12, % NAS Steatosis Inflammation Ballooning Fibrosis
Improvement 84 74 42 53 42
No change 11 26 53 42 47
Worsened 5 0 5 5 11
Mean change (SD) -2.3 (1.8) -1.1 (0.9) -0.5 (0.8) -0.7 (0.9) -0.5
45. Semaglutide vs Placebo in Obese, Nondiabetic
Patients
Post hoc analysis of randomized, double-blind phase II trial[1,2]
– Semaglutide: GLP-1 receptor agonist
– Superior, dose-related mean reductions in body weight at Wk 52 with semaglutide vs
placebo in primary analysis (6.0% to 13.8% vs 2.3%, respectively; P < .0001)[3]
ALT changes evaluated in subgroups with vs without elevated ALT at BL; 18%
(174/954) predicted to be at risk for or have NAFLD/NASH with advanced fibrosis
References in slidenotes Slide credit: clinicaloptions.com
Nondiabetic adults with BMI ≥ 30,
≥ 1 failed weight loss attempt,
A1C < 6.5%
(n = 649)*
Follow-up
to Wk 59
All patients received lifestyle intervention of -500 kcal/day diet and physical activity. *Examined population within larger trial of 957
participants from 8 countries. †Dose groups: 0.05 mg, n = 103; 0.1 mg, n = 102; 0.2 mg, n = 103; 0.3 mg, n = 103; 0.4 mg, n = 102.
Semaglutide 0.05-0.4 mg SC QD†
(n = 513)
Placebo SC QD
(n = 136)
Wk 52
46. Elevated ALT Declined, Often Normalized With
Semaglutide Treatment by Wk 52
ALT decline most marked around
Wk 28 but generally continued
through EOT with semaglutide in
patients with BL ALT elevation
By Wk 52, ALT normalized in
25% to 46% of patients receiving
semaglutide vs 18% receiving
placebo
Newsome P, et al. EASL 2018. Abstract FRI-483. Reproduced with permission. Slide credit: clinicaloptions.comEstimatedMeanALT
RatiotoBL(+SE)
1.2
1.1
1.0
0.9
0.8
0.7
0 4 8 12 16 20 24 28 32 36 40 44 48 52
Treatment Wk
0.05 mg
0.3 mg
0.1 mg
0.4 mg
0.2 mg
Placebo
Outcome at
Wk 52, % (n/n)
Semaglutide
Placebo
0.05 mg 0.1 mg 0.2 mg 0.3 mg 0.4 mg
Normalized ALT 29 (17/58) 25 (15/59) 38 (19/50) 43 (23/54) 46 (21/46) 18 (14/76)
47. clinicaloptions.com/hepatitis
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