NASH News October 2020
Fatty liver disease (FLD) and non-alcoholic steatohepatitis (NASH) are increasing in prevalence worldwide, creating a major global public health crisis. To adequately educate patients, practitioners and policy makers, there is a need to collect, curate and share relevant information. NASH News, published on behalf of the Global Liver Institute’s NASH Council, intends to meet that need and to facilitate collaboration across the emerging NASH community on a monthly basis.
We would appreciate your feedback and content contributions. Please contact nash@globalliver.org
Patient Expectations of Regulators
With the recent award of the Nobel Prize in Physiology or Medicine for the discovery of the hepatitis C virus, there is now a unique opportunity to attract interest and investment for other liver diseases - particularly NASH. In this push, science must be the determining factor with the obligation on research sponsors and investigators to conduct high-quality, unassailable research.
There must also be a strong, consistent, and trustworthy partnership with regulators who review the entirety of submissions. Regulators should bring in appropriate expertise, understand the context and impact of the disease on patients and families, and communicate in a clear, reliable, and timely manner.
Unfortunately, as the United States mounts the largest vaccination effort in its history due to the COVID-19 pandemic, there is a lack of trust between the patient community and the US Food and Drug Administration (FDA).
Most recently, the liver community was set back by a series of decisions demonstrating a lack of understanding by the FDA about the hepatology field. This started with the FDA’s Office of Immunology and Inflammation, Division of Hepatology and Nutrition (DHN) decision to cancel the Advisory Committee for the first pharmacological treatment for Nonalcoholic Steatohepatitis, obeticholic acid (OCA). DHN followed this disappointing decision on June 29th by choosing to send out a Complete Response Letter (CRL) indicating the benefits of OCA did not outweigh its risks and encouraging the continuation of the OCA outcomes study.
Soon after, the FDA’s Center for Devices and Radiological Health (CDRH) denied Orbera intragastric balloon the designation of “Breakthrough device” for the treatment of NASH on July 17th, and then the FDA sent another CRL in response to the New Drug Application (NDA) seeking approval for the investigational agent terlipressin to treat adults with hepatorenal syndrome type 1 (HRS-1) on September 14th. Both the Orbera balloon and terlipressin have been available for different indications for years.
This lack of understanding of values in hepatology puts today’s patients at risk and endangers research into complex conditions such as NASH or HRS-1. It also instills a deeper distrust in the FDA during a global public health crisis. While we understand that the current COVID-19 pandemic is putting unprecedented pressure on health systems, we cannot afford to have a regulator that does not value the patient perspective on risk/benefits in difficult times.
As patients for whom access to proper treatment is a daily life-and-death issue, it is encouraging that the FDA acknowledges the role they can play in protecting lives but disappointing to see their lack of action in addressing liver disease.
Donna R. Cryer, JD
President & CEO
Global Liver Institute
GLI LIVE Weekly
Please join the Global Liver Institute Wednesdays at 12 pm EDT for a regular Facebook Live event. Donna Cryer, Founder, and CEO of GLI will take coronavirus questions from liver patients, caregivers, and other community members. We’re here to help you stay informed.
Do you have a liver health topic or issue you would like addressed on an upcoming episode of GLI Live? If so, reach out and contact GLI LIVE. We would love to hear from you!
Recent GLI Live episodes featuring NASH include:
Beyond the Biopsy
This September, GLI launched a Beyond the Biopsy initiative to provide surround-sound and direct advocacy support to advocate for greater adoption of noninvasive diagnostics at a national level whether directly through legislative, regulatory, or coverage/reimbursement changes.
With 1 in 4 individuals predicted to have a form of nonalcoholic fatty liver disease, noninvasive diagnostics are vital to screening and diagnosis for all individuals at risk of liver disease. With easier access, lower costs, and less burden on the patient, moving away from biopsy and towards noninvasive diagnostics will benefit patients, at-risk populations, and the field.
This initiative, hosted by GLI CEO and Founder, Donna Cryer, launched with a national radio tour on August 31 and then moved online with virtual panels focusing on three states - Colorado, Massachusetts, and New York - with leading experts, policymakers, and patient advocates. The virtual events conclude September 30th with a discussion on the state of and prospects for noninvasive diagnostics.
August Radio Media Tour
August 31st: The GLI Radio Media Tour
With Mazen Noureddin, MD, Cedars-Sinai Medical Center
September: GLI LIVE
Sept: 9th: Watch GLI LIVE: Beyond the Biopsy, Colorado
With Introductory remarks by US Rep. Jason Crow (CO-6)
And Kimberly Morgan Bossley, Hepatitis C Advocate and Co-Founder, The Bonnie Morgan Foundation
Sept 16th: Watch GLI LIVE: Beyond the Biopsy, Massachusetts
With Raymond Chung, MD, President-Elect AASLD, Massachusetts General Hospital,
Mukesh Harisinghani, MD, Massachusetts General Hospital,
And Scott Linscott, Liver Transplant Patient and Advocate
Sept 23rd: Watch GLI LIVE: Beyond the Biopsy, New York
With Introductory remarks by US Rep. Adriano Espaillat (NY-13),
Scott Friedman, MD, Icahn School of Medicine at Mount Sinai
and Gerard Marinaccio, Liver Transplant Patient and Advocate
Sept. 30th: Watch GLI LIVE: Beyond the Biopsy, The Wrap Up
With GLI CEO and Founder, Donna Cryer, JD
GLI Announces The Language of NASH
The Global Liver Institute announces the release of The Language of NASH - a foundational NASH messaging framework for communication about NASH and NAFLD.
The field of NASH is evolving rapidly. This fast pace has contributed to a complex NASH story with an inconsistent lexicon, resulting in messages becoming unclear and potentially confusing for key audiences. This contributes to a lack of awareness of NASH, under-diagnosis, and a negative impact on patient outcomes.
In light of this need for consistent and meaningful terminology and messaging, the Global Liver Institute, along with our NASH Council, has developed this core NASH message framework to be used as a foundation for communication in all areas around NASH.
Patient Perspectives - Tony and Betsy Villiotti
GLI interviewed Tony and Betsy Villiotti, a patient and caregiver team. Both are 2018 GLI Advanced Advocacy Academy (A3) trainees. Tony was diagnosed in 2005 with NAFLD and received a liver transplant in March of this year with Betsy beside him every step of the way.
What do you most want people to know about life with liver disease?
Tony: As a patient proceeds through the spectrum of liver disease, [they often] have the power to make lifestyle changes that affect the progression of the disease. Make the effort to learn about how nutrition can affect your disease. A patient should also know that there are likely to be many twists in the road. Situations will pop up, seemingly out of nowhere. Most prominent is hepatic encephalopathy (HE), but ascites, edema, and other conditions can arise. Be prepared for that eventuality.
What challenges you the most, from a patient and caregiver perspective?
Tony: ...My biggest challenge during my disease progression was diet. I come from a large Italian family where holidays, weekends, and any other excuse we could come up with centered around food. [Our] view was that a fat child was a happy child. We were big consumers of white bread, red meat, and pasta. Between that and my enjoyment of Italian food, it was very hard to change my diet. I eventually came up with a rule that if I liked something it probably wasn’t good for me. Exercise was also difficult as I was frequently tired and had to really push myself to stay active. Post-transplant, my challenge has been to continue eating smaller and healthier meals.
Betsy: One of the biggest challenges I had as a caregiver was knowing what foods were affecting my husband’s disease. I did talk to nutritionists, but… [they] did not have information that was specific to liver disease and cirrhosis. After the second time he was hospitalized for HE, I finally talked with a nutritionist well-versed in liver disease. I was also unaware of the many side effects that can occur with liver disease. It was important that I paid special attention to any behavior changes in my husband even though he made a valiant effort to hide them from me. In hindsight, I realize I may have missed mild episodes of HE, blaming it [instead] on dehydration.
What inspires or motivates both of you?
Tony: In 2008, I met the family of a teenager who had liver and lung cancer and passed away. What [I’ll} never forget from meeting that family was their child’s motto: “Life isn’t about how many breaths you take; it is about what you do with those breaths.” I kept coming back to this after my transplant and it inspired me and motivated me to form a non-profit, NASH Education, [with the mission to] increase the awareness of NAFLD and NASH. My target is the person who has the same knowledge, which was none, that I had when I was diagnosed with fatty liver in 2005.
Betsy: Now that my husband has been successfully transplanted in March 2018, I am inspired by him and his effort to spread the word about NAFLD and NASH.
Learn more about Tony and Betsy Villiotti and their non-profit at NASH kNOWledge.
GLI Partner Highlight
For this edition of NASH News, GLI is spotlighting one of our newer members of the NASH Council, the Canadian Liver Foundation (CLF).
In 1969, the Canadian Liver Foundation was born out of the passion and concern of a committed group of business leaders and doctors who believed that liver disease needed a champion. With the help of volunteers, patients and families, researchers, doctors, donors, and corporate supporters who share our vision of a world without liver disease, the CLF is bringing liver research to life.
In order to attract new talent, help researchers get established, and support new advances and breakthroughs, the CLF funds the research of both senior and emerging investigators, as well as medical students. CLF assists people coping with liver disease online, in person, and via their National Help Line by answering questions after diagnosis, helping them understand their disease, and providing them with the resources they need. Through CLF’s Peer Support Network, they are connected with others who have gone through the same experience.
The Canadian Liver Foundation encourages early diagnosis and treatment by working closely with the medical community and offering tools and resources on screening and patient care. They strive to improve prevention and the quality of life of those living with liver disease by advocating for better screening, access to treatment, and patient care by working with federal, provincial, and municipal governments, community organizations, health care providers, and individuals to raise awareness of liver-related health issues and to push for policy changes.
Updates
Physical Activity, Measured Objectively, is Associated With Lower Mortality in Patients With Nonalcoholic Fatty Liver Disease
In this study from the Clinical Gastroenterological and Hepatology Journal, the association between physical activity and all-cause and cause-specific mortality from nonalcoholic fatty liver disease (NAFLD) is investigated. Over an average period of 10.6 years, increasing duration of physical activity was associated with reduced risk of death, from any cause, among individuals with NAFLD. Increasing duration of mild to vigorous physical activity was associated with a lower risk of death from any cause in individuals with NAFLD.
COVERSCAN
A joint national research program between the EU, Innovate UK, and Perspectum released preliminary data that found that in as many as half of patients, even those who were not hospitalized, COVID-19 had a damaging effect on the body's key organs.
As the world enters its eighth month living alongside this disease, it is becoming apparent that it is far more complex than that and that in some cases, devastatingly persistent. According to COVERSCAN, as many as 50% of COVID-19 patients have evidence of either heart, liver, or kidney damage. The study will look at the extent, and expected long-term impact, of Covid-19 as it continues into next year.
Screening for Nonalcoholic Fatty Liver Disease in Persons with Type 2 Diabetes in the U.S. is Cost-Effective: A Comprehensive Cost-Utility Analysis
Findings from the cost-effectiveness analysis in the journal Gastroenterology indicated that screening ≥55-year-old patients with Type 2 Diabetes for NAFLD was cost-effective, as compared to no screening, for all studied screening strategies, excluding those involving liver biopsy. Dr. Mary Rinella, a Hepatologist from Northwestern Medicine stated "these data provide additional rationale to screen for NASH in a high-risk population such as Diabetes. NASH is soon to be the primary indication for liver transplant, and it already is in women, so developing an economical approach for healthcare organizations to identify patients with the disease will become vital as therapeutics come to market."
A Case Study - Nonalcoholic Fatty Liver Disease: Making the Diagnosis
In AASLD’s Clinical Liver Disease Multimedia Review Journal, they examine a case study of a 35‐year‐old man with diabetes and a body mass index of 40 who was found to have increased echogenicity consistent with fatty liver on an ultrasound performed for right upper quadrant pain.
In summary, they conclude physicians should be vigilant about the possibility of NASH, as well as advanced stages of NAFLD, despite normal ALT levels, particularly in those with features of metabolic syndrome - suggesting that noninvasive tests should be undertaken to rule out the presence of NASH and advanced fibrosis.
How High Fructose Intake May Trigger Fatty Liver Disease
In the latest edition of NIH Research Matters, they review a study from the recent Nature Metabolism suggesting that consuming high amounts of fructose may promote nonalcoholic fatty liver disease by damaging the intestinal barrier.
Asian, Lean Patients with NAFLD have Lower Prevalence of Cirrhosis, CVD
In this study by Anna S. Lok, MD, Professor of Internal Medicine and Director of Clinical Hepatology at the University of Michigan, lean Asian patients with nonalcoholic fatty liver disease had a significantly lower prevalence of cirrhosis, cardiovascular disease, and metabolic abnormalities than lean non-Asian patients.
Lean patients had a lower risk for cirrhosis, diabetes, hypertension, or dyslipidemia, overall, when compared to those who were overweight or obese; and Asian patients, compared with non-Asian patients, had lower cirrhosis prevalence, history of CVD, cardiovascular events, and diabetes, independent of BMI.
Cost of Nonalcoholic Steatohepatitis in Europe and the USA: The GAIN study
There has been little research into the socioeconomic burden associated with nonalcoholic steatohepatitis (NASH). The Global Assessment of the Impact of NASH (GAIN) study provides real-world data on the direct medical, direct non-medical, and indirect costs associated with NASH, including patient-reported outcomes in five European countries (UK, France, Germany, Spain, and Italy) and the USA - including patient-reported outcomes in Europe and the USA, showing a substantial burden on health services and individuals.
Study shows new data on the use of breath biopsy for improved detection of liver disease
New research by the University of Birmingham has demonstrated the use of exhaled limonene as a breath-biomarker to measure liver function and disease. The positive results of the study, published in Clinical and Translational Gastroenterology, validate a probe strategy for the development of breath-based diagnostic and prognostic tests for Nonalcoholic Fatty Liver Disease and associated Nonalcoholic Steatohepatitis.
FDA Fast Tracks SSAO Inhibitor for Nonalcoholic Steatohepatitis
The Food and Drug Administration has granted Fast Track designation to TERN-201 for the treatment of nonalcoholic steatohepatitis. TERN-201, a highly-selective semicarbazide-sensitive amino oxidase (SSAO) inhibitor, is believed to work by reducing oxidative stress and recruitment of white blood cells to the liver, thereby potentially reducing inflammation and hepatic fibrosis.
Listen to GLI CEO and Founder, Donna Cryer on the Surfing the NASH Tsunami Podcast
Drug developers, investors, researchers, and corporate executives wrestle weekly to understand what is happening in the commercial development of NASH medications. Join Global Liver Institute CEO and Founder, Donna Cryer, as on the weekly Surfing the NASH Tsunami podcast - the world's leading podcast for NASH and Fatty Liver Disease.
Along with Donna, join Hepatology researcher and Key Opinion Leader Stephen Harrison, M.D., C-suite veteran Peter Traber, M.D., Founder and Medical Director of Tawazun Health Louise Campbell MSc, and Forecasting and Pricing guru Roger Green, M.B.A. as they discuss issues affecting the evolving NASH market from their own unique perspectives on the Surfing the NASH Tsunami podcast.
If you listen on Apple Podcasts, don’t forget to leave your review and rating there. What you say could ultimately help someone with fatty liver disease find hope and help!
Upcoming Events
GLI Liver Cancer Awareness Month Oct 1, 2020 – Oct 31, 2020
GLI Advanced Advocacy Academy Oct 26, 2020 – Oct 30, 2020
AASLD: The Digital Liver Meeting November 13-16, 2020
The NASH Summit December 15-18
International NASH Day June 10, 2021
