Screening for Undiagnosed NAFLD and NASH
Conditions: NAFLD, NASH - Nonalcoholic Steatohepatitis, Cirrhosis, Liver, Fatty Liver
Sponsor: Fatty liver Foundation

 
  
  
FATTY LIVER FOUNDATION 
SUNN  STUDY 
Screening for Undiagnosed NAFLD and NASH  
Wayne Eskridge, CEO 
10-5-2018  
  
  

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Table of Contents 
Screening for Undiagnosed NAFLD and NASH ........................................................................ 0 
Hypothesis ............................................................................................................................................................ 3 
Overview ................................................................................................................................................................... 3 
Objectives ............................................................................................................................................................. 5 
Questions Posed by this Study: ............................................................................................................................ 6 
Patient Selection Criteria ...................................................................................................................................... 6 
Who may participate ................................................................................................................................................ 7 
Who may not participate .......................................................................................................................................... 7 
Trial Candidate Outreach ...................................................................................................................................... 7 
Outputs of the project for the patient.................................................................................................................. 8 
Study procedures .................................................................................................................................................. 8 
Step 1: Explanation and Consent .............................................................................................................................. 8 
Step 2: Data Capture ................................................................................................................................................. 9 
Step 3: The FibroScan test ........................................................................................................................................ 9 
Step 4: Posttest process and instructions ................................................................................................................. 9 
Confidentiality .................................................................................................................................................... 10 
The FibroScan Test Procedure ............................................................................................................................ 10 
Risk/Safety Information ...................................................................................................................................... 10 
Study Oversight .................................................................................................................................................. 11 
Data Management .............................................................................................................................................. 11 
IRB Review/Ethics/Informed Consent ................................................................................................................ 11 
Intended Use of the Data ................................................................................................................................... 11 
DATA COLLECTION and ANALYSIS: ..................................................................................................................... 12 
Demographics: ........................................................................................................................................................ 12 
Metabolic Syndrome: .............................................................................................................................................. 12 
Other Health Conditions: ........................................................................................................................................ 12 
Diet: ......................................................................................................................................................................... 13 
Exercise: .................................................................................................................................................................. 13 
Alcohol: ................................................................................................................................................................... 13 
Other Liver Diseases: .............................................................................................................................................. 13 
Reporting of CAP-FibroScan Results to Participating Subjects: .......................................................................... 13 
Transient Elastography (TE): ................................................................................................................................... 14 
Controlled Attenuation Parameter: ........................................................................................................................ 14 
CAP-FibroScan Experience and Satisfaction Survey: ............................................................................................... 14 

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STATISTICAL ANALYSIS PLAN .............................................................................................................................. 16 
PRIMARY OUTCOME MEASURE .......................................................................................................................... 16 
Data Analysis ........................................................................................................................................................... 16 
Disease Staging ................................................................................................................................................... 17 
DATA COLLECTION .............................................................................................................................................. 18 
Demographics: ........................................................................................................................................................ 18 
Metabolic Syndrome: .............................................................................................................................................. 18 
Other Health Conditions: ........................................................................................................................................ 18 
Diet: ......................................................................................................................................................................... 19 
Exercise: .................................................................................................................................................................. 19 
Alcohol: ................................................................................................................................................................... 19 
Other Liver Diseases: .............................................................................................................................................. 19 
 
  
 

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SUNN  STUDY  
Screening for Undiagnosed NAFLD and NASH  
FibroScan screening, using a mobile device, of an at 
risk population to measure the liver status in 
asymptomatic people with no diagnosis of fibrotic 
liver disease  
IRB submittal flf-screen 1    date  9/27/2018  
  
Hypothesis  
This study is foundational to the screening strategy proposed so it seeks to 
define data points from which future programs can be developed.  
The hypothesis of this study is that a patient subset, unknowingly at risk for 
asymptomatic liver disease, can be drawn from patients with other chronic 
diseases. Those patients can be educated and motivated to self-select and 
engage in screening for liver disease. Post testing, they will be willing to 
state their perception of what the value of the test is to them.  
That population will yield a subset with advancing but asymptomatic 
disease.  Within that sub-population a group will exist who will proceed to 
diagnosis and be willing to learn about clinical trials. By measuring this 
response the effectiveness of the messaging about engaging diagnosis and 
follow up can be shown. There is not comparable data so this will establish 
a baseline.  
A separate track will be to measure the number of participants who enter 
the diet and lifestyle education programs. Measuring this response will also 
establish a baseline measure for the effectiveness of this messaging and 
inform future efforts.  
  
Overview  
Research has shown that there is a high incidence of undiagnosed fibrosis within 
comorbid populations as a result of the frequently asymptomatic course of NASH 

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development.  (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542082/ )  
Liver disease is a dangerous and expensive problem to manage medically with the 
cost of NAFLD estimated to exceed $32 billion per year.  
(https://www.sciencedaily.com/releases/2018/07/180703105956.htm)   
Liver disease in the form of Nonalcoholic fatty liver disease (NAFLD) and 
nonalcoholic steatohepatitis (NASH) are rapidly increasing population health 
threats driven primarily by diet and lifestyle.  Fibrotic liver disease, culminating 
in cirrhosis, is frequently asymptomatic so it is common for a patient to first 
learn of what is a life threatening condition by being told that they have 
cirrhosis.  Management and treatment of cirrhosis is complex and very costly 
with few treatment options and the only current therapy being a very expensive 
transplant for end stage liver disease.  
The position of the Fatty Liver Foundation is that this problem is magnified by 
the current American Association for the Study of Liver Disease, (AASLD), 
practice guidelines which do not advise routine screening for NAFLD.  This is the 
policy:  
Excerpts from the AASLD Practice Guidelines 2017:  
 
  
(AASLD Diagnosis Mgt NAFLD Chalasani et al 2017 Hepatology)  
  
• 
It can be argued that there should be systematic screening for 
nonalcoholic fatty liver disease, (NAFLD), at least among higher-risk 
individuals attending diabetes and obesity clinics.   
• 
Routine Screening for NAFLD in high-risk groups attending primary care, 
diabetes, or obesity clinics is not advised at this time because of 
uncertainties surrounding diagnostic tests and treatment options, along 
with lack of knowledge related to long-term benefits and 
costeffectiveness of screening.  
  
The issue of screening is complex as the result of a variety of competing needs 
and forces within society broadly and healthcare specifically. Powerful 
entrenched societal practices and counterproductive aspects of human nature 
are producing a health crisis with serious generational impact. Technology is 
moving at ever increasing speed and our systems, political and healthcare, are ill 
prepared to respond even given the best of intentions. The result is increased 
morbidity, cost, and stress.  
  
Research has established the health risks associated with liver disease and 
comorbidity with a wide range of other illnesses. (  Comorbidities and Metabolic 
Derangement of NAFLD  
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608226/  )  FibroScan has 
been shown to be a useful test to identify asymptomatic liver disease and is 

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recommended by the European Association for the Study of the Liver, (EASL) in 
the EASL CLINICAL PRACTICE GUIDELINES,   
(  http://www.easl.eu/research/our-contributions/clinical-practice- 
guidelines/detail/non-invasive-tests-for-evaluation-of-liver-disease-severity-
andprognosis/report/4  )  
  
but it has not yet been recommended by AASLD.  
  
The FibroScan device (Echosens) works by measuring shear wave velocity. The  
FibroScan device is cleared by the FDA using this technique (see attached 510(k) 
K123806). In the test, a 50-MHz wave is passed into the liver from a small 
transducer on the end of an ultrasound probe. The probe also has a transducer 
on the end that can measure the velocity of the shear wave (in meters per 
second) as this wave passes through the liver. The shear wave velocity can then 
be converted into liver stiffness, which is expressed in kilopascals. Essentially, 
the technology measures the velocity of the sound wave passing through the 
liver and then converts that measurement into a liver stiffness measurement; 
the entire process is often referred to as liver ultrasonographic elastography. 
The procedure is non-invasive and presents no bio-chemical hazards as it uses 
only well understood ultrasound technology.  
FibroScan is available and has been shown to detect advancing levels of fibrosis, 
and it is clear that nonalcoholic fatty liver disease is increasing in prevalence 
throughout the western and developing worlds.  Advancing liver disease leads to 
fibrosis, cirrhosis, and early death in a substantial portion of the population who 
could be helped with earlier lifestyle and medical interventions. 
Vibrationcontrolled transient elastography (VCTE) is a point-of-service non-
invasive technology that measures tissue elasticity and steatosis and can identify 
individuals at risk for disease progression and may therefore serve as an 
effective screening tool to alter the natural history of this disease and improve 
outcomes.   
Changing a foundational strategy, such as responding to symptoms of liver 
disease, which is the current recommendation, to one of proactively intervening 
by screening for asymptomatic disease carries a large cost burden and is difficult 
to accomplish.  
Objectives  
The goal of this screening study is to gather FibroScan data from the at-risk but undiagnosed 
population on a self-selection basis so that perceived incidence rates can be calculated and the 
economics of a single function screening service can be evaluated.  
The objective is to develop evidence based information to determine if noninvasive screening of 
at risk, comorbid people is feasible with this modality.  

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Furthermore, a secondary objective is to educate all participants about liver disease, lifestyle, 
healthy diets, and the role of clinical trials as part of the Foundation’s larger mission of being 
patient advocates.   
The value and necessity of clinical trials for the development of effective therapies is not well 
understood by the public. A goal of the foundation is to provide information about the clinical 
trial process to screening participants.  The information is of a general nature (examples are 
attached).  No specific trials will be mentioned.  The participants will also be offered the 
opportunity to receive additional general education about trials and provided with links to 
systems in which they can explore available trials should they wish to do so.  That information is 
of a general nature and no specific trials will be promoted. Participation in the screening will 
not automatically enroll them in further education as that decision is post testing and opt-in.    
  
  
Questions Posed by this Study:  
• 
What population demographics justify routine screening on a cost benefit 
basis?  
• 
The de-identified, but self-described, chronic ailments will be used with 
the scan results to broadly identify cohorts that may benefit from 
screening for asymptomatic disease.  
• 
What operating cost burden is required to sustain a mobile screening 
project and what is the minimum utilization required to justify it?  
• 
The operating costs of the study will be captured in order to inform an 
analysis of the financial constraints for deployment of mobile screening 
systems into local underserved communities.  
• 
What portion of the asymptomatic patients with advanced disease will be 
willing to learn about clinical trials?  
• 
Analysis of the posttest behavior of participants by their enrolling to learn 
more about clinical trials will measure the efficacy of using this method 
to educate the at risk population about clinical trials and ultimately 
inform decisions about how trial participants may be recruited in the 
future.  
• 
What portion of the patients take advantage of free online diet support?  
• 
Lifestyle changes are challenging as it is difficult to engage patients in the 
weeks following any testing. Tracking of the number who take advantage 
of the follow-up support will help guide future efforts to develop 
educational materials.  
  
Patient Selection Criteria  
The screening will be available to adults who self-select and who meet the inclusion criteria. 
The project will stop at 3 months or 1,000 patients, whichever occurs first. The goal is to 

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examine whether a self-referral design can serve as a cost effective patient centered wellness 
screening model.   
Who may participate  
o Adults 18 and over  
o Patients with no diagnosis of liver disease  
o Patients with any of these self-identified chronic conditions  
 Type 2 diabetes  
 Metabolic syndrome  
 Cardiovascular disease  
 Pre Diabetes  
 Sleep apnea  
 Digestive disorders  
 Osteoporosis  
 Polycystic ovarian syndrome  
 Psoriasis  
Who may not participate  
o Age less than 18  
o Pregnant women  
o Anyone with an implanted electronic device such as a 
defibrillator o Morbidly obese, BMI 40 or greater  
o Anyone not personally able to give informed consent 
o Non English speakers, no translator is available  
Trial Candidate Outreach  
The primary patient outreach efforts will be to focus on high risk comorbid patients.  We will 
communicate with local physicians to inform them that the service exists and invite them to 
refer appropriate patients to the screening facility or alternatively invite us to visit their offices 
with a portable unit.  
 The Foundation will also perform educational outreach through social media, communication 
through internet advertising, online forums, interaction with local support groups, media 
interviews and other educational efforts emphasizing the problem of our growing societal 
health crisis with obesity in general and liver disease in particular.  
It is important to emphasize that during this study the FibroScan test will be free to qualified 
patients but they will be interviewed to ask what price they would be willing to pay on a private 
pay basis. This information will be used to perform the analysis of the viability of a private pay 
model. There will be no insurance or third party payment.  Following testing the patient will be 
asked what payment amount, ranging from zero to more than $400, would seem fair to them 
as a charge. The goal is to develop perceived value measures which can inform the financial 
modeling for the development of the fully deployed business plan.  

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Outputs of the project for the patient  
All patients will receive education about liver disease as part of the intake process. Following 
the test, the patient will receive a printed output from their FibroScan test and instructions 
about next steps.  Interpretation of test results require professional medical knowledge which is 
not provided by the study.  Patients will be directed to a telemedicine system where they can 
discuss their results with professional staff and determine any next steps. Patients may elect to 
confer with their personal physician instead as is their right. Patients with test results indicating 
no active disease will be offered connections to nutrition and dietary support.  In all cases 
patients will be offered enrollment in online educational tools about diet and lifestyle.  
Patients will also be told about clinical trials and receive information about that process and 
offered access to online educational information and trial access tools if they are interested. 
Part of the outreach from the study is to educate patients about the need for clinical trials and 
to encourage learning more about it. The core message is that therapies will not be successful 
in the future without a cohort of patients who have been educated about clinical trials and are 
willing to consider participating.  We will not recruit for any particular trials but will discuss 
their value and importance to society and potentially to individual patients.  
By focusing on asymptomatic and undiagnosed liver disease the project will identify a currently 
unavailable population ideally suited for the upcoming clinical trials required for the 
development of therapies for liver fibrosis in NAFLD, NASH, and cirrhosis.  
Study procedures  
Testing will be done by appointment. Since the test itself is very fast, with a planned test 
throughput of 15 minutes, most of the visit will be taken up by the consent procedure, 
explanation of the test itself, discussion of liver disease, and distribution of literature.  
When the test schedule is created, patients will be instructed not to eat within 3 hours of their 
appointment time so that a convenient time can be chosen.  
There will be four steps in the process.   
Step 1: Explanation and Consent  
o At the intake point a staff members will explain the purpose for the study, 
provide information about liver disease, fatty liver, NASH, and fibrosis.  
o The staff member will review the inclusion/exclusion rules and confirm that the 
patient has met the 3 hour fasting rule and has not been diagnosed with a liver 
disease.  
o If inclusion criteria are met, the staff member will describe non-invasive testing 
process using the FibroScan, give the patient printed information, and explain 
that it measures both liver stiffness and fat content which their doctor can use to 
help them with any diagnosis that may be needed. It will be explained that 
FibroScan does not provide a diagnosis but is part of the information a doctor 
would use to understand the health of their liver. A sample test report will be 
used as a visual aid.  Any questions will be answered.  

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o The staff member will explain what information will be gathered and explain that 
it is demographic information only and that no personally identifiable 
information will be collected.  
o When any questions have been answered, the staff member will explain 
consent, provide the patient with the document, and answer any other 
questions.  
o Upon signing of the consent the staff member will assign a random number to 
the consent and to the patient questionnaire.  
Step 2: Data Capture  
o After signing the consent form the patient will be asked to fill out the demographic 
form which will record basic health information, height, weight, sex, age, ethnicity, 
and identify any comorbid conditions of which they are aware from a list of common 
liver related comorbidities.    
Step 3: The FibroScan test   
o The patient will take the completed intake form and the educational materials 
with them to the FibroScan test room where the test will be performed.  
o A certified FibroScan technician will double check the intake form and answer 
any additional questions that the patient may have.  
o The technician will then administer the test according to the established 
standard test procedure and will identify it with the random number assigned to 
this test in step 1.  
Step 4: Posttest process and instructions  
o When the test is complete the test results will be printed out and given to the 
patient.  
o The patient will also be given detailed information about how FibroScan is used 
and what it measures in a format that they can use to inform themselves so that 
they can better discuss the results and next steps with a physician. This will 
include explanations of how liver stiffness and fatty infiltration are defined and 
measured by the device.  
o The patient will be asked to assess their perception of the value of the test to 
them personally by indicating what they perceive the value is of the test to them 
personally on a scale from nothing to over $400.  
o The patient will also be given printed information providing ways to contact 
resources and information about lifestyle changes, free support services, and 
information about how to access additional online tools.  
o Most importantly, the patient will be instructed on how to access telemedicine 
support for interpretation of the test results and next steps. The technician will 
explain that the study provides the test, but interpretation must be done by a 
physician.  Some patients may elect to discuss it with their existing doctor but 

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they will be encouraged to utilize the hepatology services, particularly if their 
test results are elevated.  
  
Confidentiality  
Under this protocol, no personally identifiable information will be captured. The consent form 
does require that it be personally signed but that information will not be digitized.  Upon 
completion of the study the paper copy of the completed consent forms will be placed in 
secure storage.  
The test will be assigned a randomly generated ID code which will be assigned to the consent 
form and to the demographic form.  That code will connect the demographic information to the 
results of the test for analysis. In the event that a competent authority required the retrieval of 
the consent for the test, it would be possible, through the use of the ID code, to connect the 
information.  At no time will the information be stored together or be in a compatible format.  
The ID code will be keyed to the digitally stored FibroScan results database which the patient 
can provide to their physician at their discretion.  The scans will not be personally identified and 
can only accessed by the unique code. The dataset will be stored and encrypted and individual 
test results can only be retrieved using the random key code.  In this way the patient can have 
access to the test result but only the patient will be in possession of the key that accesses the 
information.  
Employees will be trained in the expectations of confidentiality and will have signLinda Lied an 
agreement to keep any patient information private as part of the hiring procedure.  
  
The FibroScan Test Procedure  
FibroScan is notable for its fast, safe, non-invasive design. This is the procedure:  
A certified FibroScan trained technician will administer the test.  
• 
A pain-free diagnostic test, FibroScan® requires no sedation of any kind.  
• 
The procedure itself usually takes about 5 minutes.   
• 
For the procedure, the patient will lie on their back with their right arm 
raised behind their head and their right abdominal area exposed.  
• 
The technician will apply a water-based gel to the skin and then place a 
non-invasive probe over the liver.  
• 
During the exam, the patient may feel a slight vibration on the skin at the 
tip of the probe as it delivers ultrasound waves to the area for measuring 
purposes.  
  
Risk/Safety Information  
There are no uncommon risks or safety concerns resulting from this procedure.  There will be 
the normal office space risks when accommodating patients with the common comorbidities 

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such as falls, nausea, paper cuts, and other normal space management concerns. None, 
however, derive from the FibroScan screening process itself.  
Study Oversight  
The principal investigator and the co-investigators will provide oversight for the project and 
assure that all procedures are followed.  The PI will assure that the staff will be properly 
qualified and trained to deliver the study information in a proper way according to the study 
protocol.  The staff will be instructed on the informed consent process, privacy policies, data 
systems, instructional materials, and patient care as examples of site management.  
Data Management  
Data collected for study purposes will be stored on a HIPAA compliant system for statistical 
analysis as part of the economic modeling of this screening process for these high risk 
populations. The anonymized data will be used by the study sponsor or a designee for analysis 
but will not be made publically accessible.  This information is not part of the patient medical 
record at this time, however, the test report the patient receives will have an ID which they 
could provide to a physician who could use it to copy the scan information into the formal 
medical record at the patient’s request.  The test data will be maintained for a period of at least 
5 years to determine its value in future research study.  
IRB Review/Ethics/Informed Consent  
As part of the intake and education process, informed consent will be explained and the patient 
will be provided with an IRB approved informed consent form describing the FibroScan process 
and what the entire process will be.  Since the FibroScan is a well-known device, the consent 
form will be consistent with non-invasive testing of this kind.  
If any unanticipated problems were to occur during the course of the research study, the PI will 
report these issues to the IRB within 10 working days.  
Intended Use of the Data  
It is the investigators belief that current standards of care guidelines of the AASLD, which do 
not, as a result of inadequate data, advise routine wellness screening for liver fibrosis in high 
risk populations likely constitutes a risk to the lives of those patients.  
Data to support a change in guidance from the AASLD does not yet exist. It is the goal of this 
study to develop data which can guide the design of a strategy which can be implemented 
privately and lend support to a change of guidance from the AASLD to recommend wellness 
screening.  
The data from the study will be used to support future financial modeling and to provide 
baselines for programs to educate patients about clinical trials, diet, and lifestyle changes 
delivered electronically. Since there is no existing measure, an a-priori power analysis is not 
overly instructive, but based on an assumed normal distribution the study seeks to enroll no 
fewer than 400 participants to yield a minimum theoretical power of around 0.8 and may 
include up to a maximum of 1,000 patients.  

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The study will also produce data on the incidence and staging of NAFLD and NASH, as indicated 
by their FibroScan scores, and will track, in aggregate, their response to information about 
clinical trials and dietary support delivered through online resources. This data will not be 
informed by the patient record as no personally identifiable data will be collected.  
The dataset will include demographic information and general ethnicity so aggregate subtotals 
of the various populations may be examined for additional insights to inform future 
investigations.  
DATA COLLECTION:  
Demographics:  
After signing the consent form the research subjects will fill out a basic form to provide demographic 
information, including sex, age, and race/ethnicity.   We will measure height and weight prior to 
CAP/FibroScan testing.   
Metabolic Syndrome:  
Subjects will use a form to check YES or NO for comorbid components of the metabolic syndrome that 
they may or may not have:   
• 
Obesity/overweight  
• 
Diabetes mellitus  
• 
Hypertension  
• 
Hypercholesterolemia   
• 
Hypertriglyceridemia  
• 
Gout or elevated uric acid  
  
Other Health Conditions:  
Subjects will use a form to check YES or NO for other health conditions they may or may not have:  
• 
Heart disease  
• 
Heart attack  
• 
Arrhythmia  
• 
Stroke  
• 
Arthritis  
• 
Osteopenia/osteoporosis  
• 
Hypothyroidism  
• 
Low Vitamin D   
• 
Low testosterone   
• 
Menopausal state  
• 
Inflammatory bowel disease (ulcerative colitis or Crohn’s disease)  
• 
Cancer o Skin: melanoma o Skin: basal cell or squamous cell cancers  
o Other type of cancers: lymphoma; leukemia; head or neck; thyroid; brain; breast; lung; 
stomach; colon; liver; ovary; uterus; prostate; bone   
  

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Diet:   
Subjects will fill out a form using a 5-point scale of the frequency of their average weekly dietary intake 
of specific food types:  (A. 0 days, B. 1-2 days, C. 3-4 days, D. 5-6 days, E. 7 days per week)   
o Proteins:  eggs, cheese, beans, fish, chicken, turkey, beef, pork  
o Starchy carbohydrates:  breads, rolls, pasta, cereals, potatoes, rice, corn, peas, lima 
beans  
o Non-starchy vegetables:  lettuces, kale, carrots, green beans, broccoli, peppers, onions, 
cucumber  
o Fats:  butter, margarine, avocado, oils (olive, safflower, cottonseed, peanut, sesame,  
walnut)  
o Nuts: peanuts, walnuts, cashews, almonds, macadamias, peanuts o Sugars or Syrups:  
sugar, high fructose corn syrup (sodas), maple or corn syrups o Fast food meals o Eating 
out at restaurants  
  
Exercise:   
Subjects will fill out a form using a 5-point scale of the frequency of their average weekly exercise:    
(A. 0 days, B. 1-2 days, C. 3-4 days, D. 5-6 days, E. 7 days per week)  o Cardiovascular: brisk 
walking, jogging, biking, treadmill, stationary bike, stair stepper, elliptical, 
swimming laps o Strength: weight lifting, resistance machines or cords  
  
Alcohol:    
Subjects will fill out a form quantifying their average weekly total of alcoholic drinks:   
( 1 drink= 12 oz. beer, 6 oz. wine, 1.5 oz. hard liquor; 3 oz. brandy, sherry, liqueur):   
o None  o 1-2 drinks/week o 3-4 drinks/week o 5-6 drinks/week o 
7 -8 drinks/week o 9-10 drinks/week o 10-12 drinks/week o 13-14 
drinks/week o 14-20 drinks/week  
o 21 or more drinks/week  
  
Other Liver Diseases:  
Subjects will check YES or NO for other liver-related diseases that they may or may not have:  
o Hepatitis B alone o Hepatitis B with Hepatitis D o Hepatitis C o Hepatitis E 
o Autoimmune hepatitis o Primary biliary cholangitis o Primary sclerosing 
cholangitis o Iron overload  
o Alpha-1-antitrypsin deficiency  
  
Reporting of CAP-FibroScan Results to Participating Subjects:  
A trained individual will perform the CAP-FibroScan according to the FDA-approved, manufacturer’s 
protocol. A licensed hepatologist will determine the degree of fibrosis and will review the results and 
the steatosis based on the values in the following tables:    
  

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Transient Elastography (TE):  
  
  
  
Disease  
F0-F1  
F2  
F3  
F4  
   
NAFLD/NASH  
  
  
≤ 7.0  
  
≤ 7.5  
  
≤ 10.0  
  
≤ 14.0  
Reference: Current Gastroenterology Reports. 2014; 16: 372  
  
TE Interpretation:  The subject’s liver stiffness score in kPa units shows:  
• 
F0:    No liver fibrosis   
• 
F1-2: Mild-Moderate liver fibrosis   
• 
F3:    Severe liver fibrosis   
• 
F4:     Cirrhosis   
  
Controlled Attenuation Parameter:   
  
Steatosis 
Grade  
% Steatosis on 
Liver Biopsy  
CAP 
Value  
  
Mild (S1)  
  
5-33%  
  
225-275 dB/M  
  
Moderate  
(S2) to  
Severe (S3)  
  
>33%  
  
>66%  
  
  
275-400 dB/M  
Reference: World J Gastroenterol. 2016; 22: 7236  
  
CAP-FibroScan Experience and Satisfaction Survey:  
Subjects will be asked to complete a survey about their experience after having the CAP-FibroScan and 
hearing their results, using a 5-point scale:  very likely—likely—neither likely nor unlikely—unlikely--very 
unlikely.   
1. Having completed the CAP-FibroScan and obtained your results, how likely are you to:  
• 
recommend this test to a friend or family member?  
• 
share your results with your doctor?  
• 
consult with a liver specialist?  
• 
seek information about FDA-approved clinical trials of therapies for non-alcoholic fatty liver 
disease?  
  
Subjects will be asked to assess their level of satisfaction with the CAP-FibroScan procedure after being 
informed of their results, using a 5-point scale:  very satisfied—satisfied—neither satisfied nor 
dissatisfied—dissatisfied—very dissatisfied.   
2. Having had the CAP-FibroScan and obtained your results, how satisfied are you with the 
procedure?   
a. If you answered very satisfied or satisfied, please check all the reasons for your answer:   

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• 
Ease of scheduling appointment for procedure.  
• 
Scheduled procedure occurred on time.   
• 
Cleanliness of the facility.   
• 
Professionalism and friendliness of staff.  
• 
Understandable explanation of the procedure and sufficient answers to my questions.  
• 
Quality of explanation of the results and quality of the answers to your questions about 
the results.  
• 
Comprehensive discussion of options my future care.  
  
b. If you answered dissatisfied or very dissatisfied, please check all the reasons for your 
answer:   
• 
Lack of ease of scheduling appointment for procedure.  
• 
Procedure did not occur on time.   
• 
Problems with the cleanliness of the facility.   
• 
Problems with the professionalism or friendliness of staff.  
• 
Inadequate explanation of the procedure and deficient answers to my questions.  
• 
Inadequate explanation of the results and deficient answers to my questions about the 
results.  
• 
Inadequate discussion of options for my future care.  
  
3. Having had the CAP-FibroScan and obtained your results, how satisfied are you that the 
procedure provided useful information about your health?   
a. If you answered very satisfied or satisfied, please check all the reasons for your answer:   
• 
I understand what the CAP-FibroScan measures.   
• 
I understand how much fat I have within my liver.  
• 
I understand if I have or do not have evidence of scarring (fibrosis) of my liver.  
• 
The results gave me a better understanding of my liver health.  
• 
The discussion provided useful information about FDA-approved clinical trials of 
therapies.  
• 
The discussion of my liver health will help me obtain better health care for my liver.  
  
b. If you answered dissatisfied or very dissatisfied, please check all the reasons for your 
answer:   
• 
I do not understand what the CAP-FibroScan measures.   
• 
I do not understand how much fat I have within my liver.  
• 
I am not sure if I have or do not have scarring (fibrosis) of my liver.  
• 
The results did not give me a better understanding of my liver health.  
• 
The discussion did provide useful information about FDA-approved clinical trials of 
therapies.  
• 
The discussion of my liver health is unlikely to help me obtain better health care for my 
liver.  
  

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SUNN STUDY 
STATISTICAL ANALYSIS PLAN 
PRIMARY OUTCOME MEASURE – DETERMINE THE INCIDENCE AND STAGING OF 
UNDIAGNOSED NAFLD AND NASH IN A HEALTH CONSCIOUS SELF SELECTED 
POPULATION AS MEASURED WITH A FIBROSCAN 
 
The study will measure the incidence and severity of the fat content and liver stiffness in an at 
large, self selected population who do not, at the time of testing, have a diagnosis of NAFLD, 
NASH or other liver disease.  This will measure the incidence of undiagnosed liver disease and 
the statistical distribution of the disease staging in this population. 
 
A key secondary outcome measure will be the incidence and disease distribution as a function 
of ethnicity. 
 
We will analyze data using a standard statistical software package, Stata® 12.1 (Stata Corp, College 
Station, TX).  We will express continuous variables using the mean ± standard deviation, and we will test 
the null-hypothesis using the Student t-test.    We will compare categorical variables using contingency 
table analysis. For all statistical tests, we will define a two-sided p-value of ≤0.05 as statistically 
significant.  We will perform multivariate analysis of all risk factors found to be statically significant (p 
≤0.05) using univariate analysis.   
 
Data Analysis   
We will record all data in a Microsoft Excel worksheet.  We will sequentially number each participating 
subject.  We will not record any identifying information (e.g., names, initials, DOB, SSN, insurance, EPIC 
MRNs) in the database.  Thus, all data assessments will maintain the anonymity of all participating 
subjects.   
 
1. The primary goal is to calculate the proportion of men and women that when tested have CAP-
FibroScan evidence of:    
• 
No fat or liver stiffness  
• 
No fat but evidence of liver stiffness  
• 
Fat without liver stiffness  
• 
Fat with liver stiffness  
o Stiffness values indicative of cirrhosis  
o Stiffness values indicative of fibrosis without cirrhosis   
NOTE: no individual follow up or track will be done as not personally identifiable information will be 
captured or retained. 
  

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2. The secondary goal is to determine factors that are statistically significantly associated with the 
presence or absence of fat with or without increased liver stiffness.   
We will analyze data using a standard statistical software package, Stata® 12.1 (Stata Corp, College 
Station, TX).  We will express continuous variables using the mean ± standard deviation, and we will test 
the null-hypothesis using the Student t-test.    We will compare categorical variables using contingency 
table analysis. For all statistical tests, we will define a two-sided p-value of ≤0.05 as statistically 
significant.  We will perform multivariate analysis of all risk factors found to be statically significant (p 
≤0.05) using univariate analysis. 
 
This exploratory goal seeks to determine the degree of satisfaction of subjects who undergo a screening 
CAP-FibroScan free of charge.    
 
We will calculate the frequency of answers for each of the five items reflecting subjects’ 
likelihood of:  
• 
recommending this test to a friend or family member.  
• 
sharing their results with their doctor.  
• 
consulting with a liver specialist.  
• 
seeking information about FDA-approved clinical trials of therapies for non-alcoholic fatty liver 
disease.  
• 
 
We will not perform statistical analyses for these descriptive data.   
Disease Staging 
The disease staging to be analyzed will be based upon these breakpoints from the FibroScan 
test. The test scores will be translated into these staging ranges for analysis. 
 Transient Elastography (TE):  
  
  
  
Disease  
F0-F1  
F2  
F3  
F4  
   
NAFLD/NASH  
  
  
≤ 7.0  
  
≤ 7.5  
  
≤ 10.0  
  
≤ 14.0  
Reference: Current Gastroenterology Reports. 2014; 16: 372  
  
TE Interpretation:  The subject’s liver stiffness score in kPa units shows:  
• 
F0:    No liver fibrosis   
• 
F1-2: Mild-Moderate liver fibrosis   
• 
F3:    Severe liver fibrosis   
• 
F4:     Cirrhosis   
  
 
 

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Controlled Attenuation Parameter:   
  
Steatosis 
Grade  
% Steatosis on 
Liver Biopsy  
CAP 
Value  
  
Mild (S1)  
  
5-33%  
  
225-275 dB/M  
  
Moderate  
(S2) to  
Severe (S3)  
  
>33%  
  
>66%  
  
  
275-400 dB/M  
Reference: World J Gastroenterol. 2016; 22: 7236  
 
 
DATA COLLECTION  
Demographics:  
The data for analysis will be captured by these patient completed forms to provide demographic 
information, including sex, age, and race/ethnicity.   We will measure height and weight prior to 
CAP/FibroScan testing.   
Metabolic Syndrome:  
Subjects will use a form to check YES or NO for comorbid components of the metabolic syndrome that 
they may or may not have:   
• 
Obesity/overweight  
• 
Diabetes mellitus  
• 
Hypertension  
• 
Hypercholesterolemia   
• 
Hypertriglyceridemia  
• 
Gout or elevated uric acid  
  
Other Health Conditions:  
Subjects will use a form to check YES or NO for other health conditions they may or may not have:  
• 
Heart disease  
• 
Heart attack  
• 
Arrhythmia  
• 
Stroke  
• 
Arthritis  
• 
Osteopenia/osteoporosis  
• 
Hypothyroidism  
• 
Low Vitamin D   
• 
Low testosterone   
• 
Menopausal state  
• 
Inflammatory bowel disease (ulcerative colitis or Crohn’s disease)  
• 
Cancer o Skin: melanoma o Skin: basal cell or squamous cell cancers  

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o Other type of cancers: lymphoma; leukemia; head or neck; thyroid; brain; breast; lung; 
stomach; colon; liver; ovary; uterus; prostate; bone   
  
Diet:   
Subjects will fill out a form using a 5-point scale of the frequency of their average weekly dietary intake 
of specific food types:  (A. 0 days, B. 1-2 days, C. 3-4 days, D. 5-6 days, E. 7 days per week)   
o Proteins:  eggs, cheese, beans, fish, chicken, turkey, beef, pork  
o Starchy carbohydrates:  breads, rolls, pasta, cereals, potatoes, rice, corn, peas, lima 
beans  
o Non-starchy vegetables:  lettuces, kale, carrots, green beans, broccoli, peppers, onions, 
cucumber  
o Fats:  butter, margarine, avocado, oils (olive, safflower, cottonseed, peanut, sesame,  
walnut)  
o Nuts: peanuts, walnuts, cashews, almonds, macadamias, peanuts o Sugars or Syrups:  
sugar, high fructose corn syrup (sodas), maple or corn syrups o Fast food meals o Eating 
out at restaurants  
  
Exercise:   
Subjects will fill out a form using a 5-point scale of the frequency of their average weekly exercise:    
(A. 0 days, B. 1-2 days, C. 3-4 days, D. 5-6 days, E. 7 days per week)  o Cardiovascular: brisk 
walking, jogging, biking, treadmill, stationary bike, stair stepper, elliptical, 
swimming laps o Strength: weight lifting, resistance machines or cords  
  
Alcohol:    
Subjects will fill out a form quantifying their average weekly total of alcoholic drinks:   
( 1 drink= 12 oz. beer, 6 oz. wine, 1.5 oz. hard liquor; 3 oz. brandy, sherry, liqueur):   
o None  o 1-2 drinks/week o 3-4 drinks/week o 5-6 drinks/week o 
7 -8 drinks/week o 9-10 drinks/week o 10-12 drinks/week o 13-14 
drinks/week o 14-20 drinks/week  
o 21 or more drinks/week  
  
Other Liver Diseases:  
Subjects will check YES or NO for other liver-related diseases that they may or may not have:  
o Hepatitis B alone o Hepatitis B with Hepatitis D o Hepatitis C o Hepatitis E 
o Autoimmune hepatitis o Primary biliary cholangitis o Primary sclerosing 
cholangitis o Iron overload  
o Alpha-1-antitrypsin deficiency