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

NASH in the Time of Coronavirus: Assess, Adjust, Adapt

The novel coronavirus pandemic has put a harsh spotlight on the gaps and deficiencies in our public health and healthcare infrastructures, necessitating the mobilization of front-line clinicians, researchers, manufacturers, patient advocates, and government officials.

The Global Liver Institute has surely risen to the challenge of developing a unique COVID-19 Response for Patients with Liver Disease, Transplant, or Cancer program to provide timely, actionable information and advocacy for liver patients. However, this is not the time to lose momentum in catalyzing our global movement to combat NASH. It is time to assess the new global landscape, adjust to the changes in circumstances and mood, and adapt with creative solutions. It is time to do even more.

In the upcoming weeks:

Recognize that Indian pharmaceutical company Zydus Cadila has obtained the first-ever medication approved for NASH, Saroglitazar, a drug that has already been approved for diabetes-related conditions. At this time, the approval is limited to India.
Ensure trial continuity for NASH clinical trials, look to the FDA and IRBs for permissible modifications that keep both patients and researchers safe from COVID-19, including changes in visit schedules and integration of mobile or telehealth technology.
GLI NASH Council ICER Task Force is responding to ICER’s newly extended comment period for the draft evidence report on the clinical effectiveness and value of Intercept Pharmaceuticals OCA drug for the treatment of NASH. Issued on March 18, due to COVID-19, ICER has extended the public comment period to June 24.
Reinventing International NASH Day from a one day awareness/event day into a multi-platform experience. Stay tuned for an announcement of the full new schedule!

Donna R. Cryer, JD
President & CEO
Global Liver Institute

Updates

Zydus announces world’s first drug for the treatment of Non-Cirrhotic NASH

Zydus Cadila, an innovation-driven global pharmaceutical company, announced that the Drug Controller General of India has approved it's New Drug Application for Saroglitazar for the treatment of Non-Cirrhotic Non-Alcoholic SteatoHepatitis in India. Saroglitazar 4 mg demonstrated a significant reduction in liver fat, liver enzymes and disease activity.

FDA Announces New Guidance for Clinical Trials During COVID-19 Pandemic

The FDA issued guidance on clinical trials during the novel coronavirus (COVID-19) pandemic for industry, investigators, and institutional review boards (IRBs). The guidance emphasizes patient safety, compliance with good clinical practice, and maintaining the integrity of clinical trials.

In 2017, the FDA’s Center for Drug Evaluation and Research embarked on an initiative to modernize the New Drugs Regulatory Program

That reorganization is now complete. The Office of New Drugs (OND) now comprises six cross-functional support offices and eight clinical offices. The eight clinical offices oversee OND’s 27 clinical divisions and six pharm/tox review divisions. Included in this is the new Division of Hepatology and Nutrition with Joseph Toerner, MD, MPH as Acting Division Director.

NGM's NASH drug cuts liver fat, inflammation, scarring in phase 2, shares surge

Last fall, NGM Bio unveiled data from a small group of patients showing its NASH drug cut liver fat in a phase 2 study. Now, the company is reporting results for all 78 patients in the study, showing the treatment beat placebo at reversing liver scarring and inflammation, as well as reducing liver fat buildup.

Worldwide trends in insufficient physical activity from 2001 to 2016: a pooled analysis of 358 population-based surveys with 1·9 million participants

Insufficient physical activity is a leading risk factor for non-communicable diseases and has a negative effect on mental health and quality of life. We describe levels of insufficient physical activity across countries and estimate global and regional trends.

A Novel Cause of Fatty Liver in Lean People

The worldwide epidemic of NAFLD is thought to mainly be driven by an unhealthy lifestyle with little physical activity and a diet high in saturated fats, sugar, and fructose. In these overweight and obese patients, weight-loss brought about by lifestyle modification is considered most effective and safe to treat NAFLD and reduce the risk of advanced forms of liver diseases, such as cirrhosis or liver cancer, type 2 diabetes and cardiovascular diseases. However, EurekAlert reports a case of a 45 year old woman who received immune checkpoint blockade therapy for skin cancer which may have triggered inflammation of her subcutaneous fat, resulting in a dramatic loss of fat mass and severe NAFLD.

Liver Fibrosis Tied to Poorer Health Outlook in Those With Fatty Liver Disease

Among people with non-alcoholic fatty liver disease, the presence of liver fibrosis is associated with poorer liver-related health outcomes as well as a higher risk of death, MedPage Today reports. This finding from a recent review and meta-analysis of numerous studies also held true for the subset of those people with the more severe form of fatty liver disease, non-alcoholic steatohepatitis.

FNIH and Perspectum Biomarkers on FDA Website

Perspectum Diagnostic’s biomarker to identify patients who are more likely to have liver histopathology for nonalcoholic steatohepatitis is now in transition to the 507 process at the FDA. Section 507, the Qualification of Drug Development Tools, of the Federal Food, Drug, and Cosmetic Act includes transparency provisions that apply to requestors’ submissions and the FDA’s formal written determinations in response to such submissions. The Foundation for the National Institutes of Health Biomarkers Consortium received FDA acceptance into the CDER Biomarker Qualification Program for four diagnostic enrichment biomarkers (NIS-4, OWL, PRO-C3-PRO-C6, ELF) intended, along with clinical factors, to identify patients likely to have liver histopathologic findings of nonalcoholic steatohepatitis and with a nonalcoholic fatty liver disease activity score (NAS) ≥4 and liver fibrosis stages 2 or 3.

Deaths to double from fatty liver disease: Child obesity the main driver

Australia is facing an “epidemic” of non-alcoholic fatty liver disease, with 30,000 deaths predicted over the next decade, according to a modeling study from the University of Western Australia. The trend is largely being driven by childhood obesity and the consumption of sugary drinks.

Potentially Deadly Liver Disease Caused by Belly Fat - here's how to zap it

The UK Mirror tabloid reports that with rising obesity levels, a third of the UK population now has non-alcoholic fatty liver disease, the medical term for too much fat building up in your liver. They highlight one woman’s efforts to reduce her disease risk.

Secondhand Smoke May be Abetting the Rise of Chronic Liver Disease in Children and Adults

Smoke exposure can alter how the liver processes fats, according to lab research, ultimately contributing to nonalcoholic fatty liver disease.

NASH in Diabetes: New Therapies on the Horizon

Much of the focus on diabetes complications centers on cardiovascular disease and chronic kidney disease, but a Medscape review finds a fast-emerging area of inquiry is the association of diabetes with liver disease—specifically nonalcoholic fatty liver disease and its progressive form, nonalcoholic steatohepatitis. Although a number of promising therapies for NASH are in the pipeline, current treatment options are limited. What is the clinical burden of NASH, especially as it pertains to diabetes, and what can be done about it?

Noninvasive Markers of Liver Disease May Improve Referrals, Predict Complications in Diabetes

With the use of age-adjusted thresholds for noninvasive markers of liver steatosis and fibrosis, patients with type 2 diabetes (T2D) may be referred more efficiently to specialists, according to study results published in BMJ Open Diabetes Research & Care. Furthermore, the researchers found a consistent association between these markers and chronic complications of T2D.

4 Questions About the Diagnostic Challenges in NAFLD

With new pharmacologic treatment options on the horizon for NAFLD and NASH, a Q&A section in Gastroenterology Consultant with Duke Medical School physician Manal Abdelmalek highlights key takeaways for specialists about the current diagnostic and staging methods for these diseases.

Revolutionizing Liver Disease Diagnosis: Arrow Dx Drives Artificial Intelligence to Diagnose Liver Disease

Check out the latest from GLI, Liver Matters - a series of interviews highlighting the need for cutting edge alternatives to liver biopsy - a painful, risky, invasive procedure long considered a standard for diagnosing liver diseases such as fatty liver disease and non-alcoholic steatohepatitis.

NAFLD/NASH Coding Update

LabCorp now offers testing options to help identify NAFLD and NASH, including:

NAFLD Cascade (402205)

The NAFLD Advanced Rule-Out Cascade is intended for use in patients with NAFLD and suspected NASH with advanced fibrosis that include subjects with no alcohol-related disorders and any of the following: elevated liver function tests, obesity, type 2 diabetes, metabolic syndrome, imaging evidence of fat accumulation, dyslipidemia, polycystic ovary syndrome.

FIB-4 With Reflex to NASH FibroSure® (402070)

The FIB-4 index is reported to be a simple, accurate, non-invasive, and readily available laboratory test index that can help in the evaluation of patients with HCV and Nonalcoholic Fatty Liver Disease.

Liver Fibrosis Risk Profile With Hepatic Function Panel, Complete Blood Count With Differential, FIB-4, and APRI (402145)

This profile is intended for use in screening patients suspected to be at risk for liver fibrosis.

Patient Perspective

“We always think that we are invincible until we learn that what we put into our bodies matters.” – Melanie Braga

A routine physical became more than I nervously anticipated as the doctor informed me that I had “non-alcoholic fatty liver disease (NAFLD).” As I saw the words come out from my doctor’s mouth, my mind started racing with so many questions. How could this be? How did I let myself get to this point? Am I going to be okay?

I was all too familiar with liver health as my husband had been diagnosed with NAFLD five years ago. Not to mention that prior he was diagnosed with Wilson’s Disease; a hereditary liver disease. Therefore, I knew what was good and what was not good for our livers. But I never thought it could have happened to me!

Before Diagnosis

Before being diagnosed, like many parents, I juggled it all. Two part-time jobs, a successful blog, motherhood, and daily life. It was taking a toll on me, and when I am overwhelmed, I seek comfort food. Of course, all the comfort food was not healthy, and in order to feel energized, I turned to pop. Little did I know that this was a temporary solution with internal consequences.

Even though I felt energized, the crash later made me feel worse and I felt more tired than ever before. I thought this was just a result of being stretched too thin and didn’t think twice about what I was doing to myself. But again, I just had to keep going for my family. Excuse after excuse that I gave to myself as to why I had to have that one French fry or that cold glass of pop. It was the only way to reason with myself that I was doing this to keep up with the high demands of life.

During Diagnosis

The first round was blood work. Once that came back with high levels of ALT, the doctor requested to re-test the following month. When those results came back a bit higher than the previous month, the doctor knew that it was NAFLD and requested further testing in three months. This was the wake-up call that I needed to realize that what I was doing wasn’t helping my family, but instead, was destroying me. How could I be there for my family when I wasn’t taking care of myself? Read more about Melanie and her fatty liver journey at the Canadian Liver Foundation.

GLI Partner Highlight

Conference Highlight: Charleston Metabolic Disorders Conference

Current and emerging best practices for the management of obesity, diabetes, non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease will be the focus of the Charleston Metabolic Disorders Conference: An Interdisciplinary Update on the Management of the Metabolic Syndrome. The conference is expected to be held on June 26-28, 2020, at the Kiawah Island Conference Center in Kiawah Island, SC.

The conditions mentioned above are seen by all physicians and are often not captured or underdiagnosed. The aim of the conference is to bring attention to these common disorders and the need for early identification of those at highest risks (e.g., NAFLD - how to identify, when to refer, how to manage, etc.). The Medical University of South Carolina designates this live activity for a maximum of 13.0 AMA PRA Category 1 Credit(s)™. View the conference agenda and read a list of the faculty who will speak at the event. Early-bird registration rates are available until April 26, 2020. Register today!

Clinical Trials

209 clinical trials globally recruiting for NAFLD
202 clinical trials globally recruiting for NASH

NASH News March 2020