September NASH News
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.
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The plan for Fall 2018
We hope that everyone had a wonderful summer. We had several fantastic calls getting to know our NASH Council Members better and using that intelligence to plot the path forward. Specifically, we are redesigning the NASH Council workgroups to be more closely linked to specific outputs and so are seeking participation in:
Lifestyle Intervention Pilot development with Baylor
Given that over 85 million people in the US have some form of fatty liver disease, we feel a duty to develop a scalable evidence-based community-driven solution for those millions who will be diagnosed with a fibrosis level of 0 to 2. Many in this group will also have a BMI greater than 30, type 2 diabetes, hypertension, and/or hyperlipidemia. A first call for this workgroup will be held on September 19, 4-5 p.m. EDT.
Picking up on the discussion at the June 1 meeting - what is the optimal screening, management, and workflow pattern between primary care, endocrinology/cardiology, and GI/hepatology? Our new NASH Council members from the American College of Physicians (ACP) will help us lead this call in October. Look for an email with the date/call-in information.
We have had conversations in the U.S. and Europe, participated in one congressional briefing, and see the need to unite the community in a more detailed discussion of what constitutes the essential elements of a NASH policy agenda and to prioritize realistic objectives. We would like to have a DC face-to-face meeting with government affairs staff in December to work through creating this agenda after the midterm elections.
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Advanced Advocacy Academy
This weekend, we are hosting our second annual Advanced Advocacy Academy (A3) at Georgetown Law School in Washington, D.C. We expect more than 20 students to attend and learn how to become liver health spokespersons, with a focus on NAFLD, NASH and liver cancer. Find out more information on our website or email us at firstname.lastname@example.org to find out how you can apply for next year’s A3 session.
American Association for the Study of Liver Diseases (AASLD)
We will be attending the American Association for the Study of Liver Diseases (AASLD)’s The Liver Meeting 2018 in San Francisco on November 9-13. Hold the date for Friday, November 9 for a GLI evening event.
New Member: Baylor Scott & White Health
We welcome Baylor Scott & White and the leadership of Dr. Don Wesson, internal medicine physician and nephrologist to the NASH Council. The team at Baylor is lending their expertise in community-driven and faith-based initiatives around weight management and diabetes control to our NAFLD/NASH efforts. Learn more in our new lifestyle intervention workgroup.
American College of Physicians
NAFLD was declared the 21st century epidemic in liver disease at the 2018 annual meeting of the American College of Physicians which featured a presentation by Zobair Younossi, MD. His presentation noted prevalence of NAFLD among adults is projected to increase by nearly 9% over the next 12 years, resulting in an increase in NASH and cirrhosis prevalence as well. CDC reports that a 43% increase in the death rate from liver cancer since 2000 has arisen along with the obesity epidemic, even as overall cancer deaths in the US have decreased.
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More than a quarter of adults with NAFLD are presumed to have NASH, which is indicated by elevated aminotransferase (ALT) levels in the blood and the absence of other identifiable causes of liver damage.
Source: Diehl AM, Day C, Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis, NEJM, 2017; 377:2063-72
Three non-invasive biomarkers have been identified as indicators of liver health and drug efficacy for clinical trials. Iron-corrected T1, or cT1, shows promising potential as researchers look to move away from liver biopsies as the gold standard for diagnosing and grading NASH. The lead doctors on this study have hope that cT1 will be useful in the future for long-term monitoring of liver health.
Richard Johnson, a researcher at the University of Denver, discovered that essential fructosuria, a rare genetic disorder that results in an inability to break down fructose, may correlate to a significantly reduced risk of obesity and type 2 diabetes. His finding inspired Pfizer to start clinical trials with a drug that is a fructose inhibitor. If this treatment works, the pill could be taken daily to prevent build-up of fat in the liver and help treat NASH.
A Key Opinion Leader meeting was held on Sept. 7 regarding a new drug in phase 3 clinical trials with the potential to help treat NASH. The same drug, PBI-4050, is also in phase 2 clinical trials to examine its effects on metabolic syndrome. There is promising data that it is hepatoprotective, reduces insulin resistance, and decreases fibrosis. It appears to have broad pharmacological and therapeutic potential.
Researchers from the Cleveland Clinic and the Texas Liver Institute are working together to create a new online calculator to predict the amount of liver fibrosis in diabetics and determine the optimal cut-off score to indicate a need for a biopsy. Six variables are considered to grade a patient on a scale of 0 to 100, with higher scores indicating more advanced liver fibrosis.
A recent study conducted by Dr. Selvakumar and his team at the Cleveland Clinic found that lean adolescents with suspected NAFLD displayed different metabolic syndrome components from healthy lean adolescents. Low HDL-C, hypertriglyceridemia, and insulin resistance were significantly more frequent in adolescents with suspected NAFLD. This indicates a need to look at all adolescents and suggests that there is a phenotypic basis for some cases of NAFLD, which differs from obese NAFLD.
Researchers at University of California, San Diego received a $12 million, four-year grant to continue their work with clinical data for patients in clinical trials. This lab focuses on, among other things, diseases that affect the liver, which includes NASH. Their work helps identify what specific pathways are affected in certain diseases and identifies new targets for drugs.
Update on GLI’s request to modify ICD-10
GLI along with Dr. Arun Sanyal of Virginia Commonwealth University petitioned CDC’s ICD-10 Coordination and Maintenance Committee to consider revisions to enable liver fibrosis to be classified more accurately and more consistently with current clinical perspectives and documentation, particularly in the context of nonalcoholic steatohepatitis (NASH). In response, Dr. David Berglund, Medical Officer for Classification and Public Health Data Standards at the National Center for Health Statistics, said they hope to present this request at the Committee’s March 2019 meeting.
Research & Studies
With NAFLD research increasing in volume and interest around the world, we are including a selection of some of the excellent studies being reported:
A team of researchers from Australia, Japan, the UK, and Denmark, have identified a noninvasive biomarker, PRO-C3, that helped identify advanced fibrosis in 92% of patients. They are working on developing a score using this biomarker and other clinical data to determine if a patient has NASH.
Researchers studied a large population in northern China and found that people with higher volumes of epicardial adipose tissue (EAT) had a statistically significant correlation with higher incidence of NAFLD and cardiovascular risk factors.
The ratio of non-HDL-cholesterol to HDL-cholesterol was a statistically significant and independent predictor of new-onset NAFLD in both Chinese males and females. The results were consistent with studies suggesting that there is a cause-effect relationship between dyslipidemia and NAFLD. This is the first study to definitively demonstrate this relationship, providing evidence for a more effective biomarker of NAFLD in at-risk individuals, as opposed to traditional blood lipid parameters.
Patients with NAFLD that were part of a lifestyle intervention program were more likely to achieve NAFLD remission compared to NAFLD patients that received the standard care. This was seen in patients with and without obesity.
Researchers from two medical schools in Japan determined that interrupting six hours of sleep in mice resulted in fat formation and insulin resistance within their livers. They examined the related molecular mechanism and identified certain genes of interest that were expressed differently among the sleep-deprived mice versus the control group. This study was highlighted as one of this month's "best of the best" as part of the American Physiological Society's APSselect program.
Quantitative MRI can differentiate between NASH and simple steatosis [SS]. This is a noninvasive way to distinguish between the two conditions, as recent studies have indicated that NASH is pathologically more severe than SS.
Recent findings indicate a statistically significant link between NAFLD and coronary artery calcification. This suggests that there is a need for coronary artery disease screening in NAFLD patients, and also reinforces the point that NAFLD is a greater public health concern than its potential to develop into NASH.
Giving mice trehalose, a sugar derived from corn starch, can activate a gene that improves insulin sensitivity in the liver, according to researchers at Washington University School of Medicine. This gene allows for better use of insulin, increased calorie burning, reduced weight gain and fat accumulation, as well as providing protection against metabolic disease.
NASH In The News
California passed a bill at the end of last month requiring the default drink offered to children in restaurants to be restricted to milk, water, sparkling water, flavored water, or nondairy milk alternative. Additionally, the default drink must be featured on menus or in advertisements for the restaurant instead of soda. This is in California’s latest effort to combat the obesity epidemic.
Last spring, California included coffee under Proposition 65, which labels known carcinogens with a cancer warning label. A proposition to exempt coffee from this law was recently introduced on the grounds that coffee has known health benefits; acrylamide, a natural substance but suspected carcinogen, does not have enough evidence to be ruled a true carcinogen and is only produced as a byproduct of roasting. The FDA released a statement upholding the exemption of coffee from cancer warning labels.