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Global Advantage Statement: Oncoustics AI -Platform Expansion in Liver Disease

JANUARY 20, 2025

"We see Oncoustics with its novel AI-based imaging technology, as ideally positioned to provide inexpensive, reliable and effective screening tools for the current and expanding epidemic of liver diseases afflicting all global regions, particularly fatty liver."

Samuel S. Lee, MD, FRCPC, FAASLD
Professor of Medicine (Hepatology)
University of Calgary, Canada

Diagnostic tests for liver disease are often complex, invasive, expensive, or limited in availability, hindering widespread adoption. Oncoustics' technology addresses this challenge by providing an easy-to-use solution for detecting and monitoring liver conditions such as steatosis, inflammation, fibrosis, and liver cancer. Unlike traditional approaches that rely on qualitative assessments by specialized MDs like radiologists, our purely quantitative approach allows any clinician to perform the exam and gain clinical insights for better-informed diagnostics and treatment planning. Our technology enables non-invasive, cost-effective, and rapid full liver tissue characterization using a handheld ultrasound device.

What sets Oncoustics apart is its hardware-agnostic approach and unique database of raw RF signal data, rather than traditional images. With the world's largest database of liver ultrasound raw RF data, collected through partnerships with hospitals and clinics worldwide, Oncoustics’ software transforms handheld ultrasound devices into powerful liver diagnostic tools, providing high-value liver diagnoses in just a five-minute workflow. Oncoustics’ approach provides a stage shift from the standard of care by providing screening to high-risk patient populations at the point of care, for earlier intervention and better outcomes. With OnX, clinicians can perform the exam and receive a resultant quantitative liver score at POC, giving them much needed insight for planning therapeutic interventions.

Competition and Diagnostics as Usual

Current preventive approaches to catch asymptomatic liver steatosis, fibrosis and inflammation early are complex and time consuming, with several appointments and specialists involved. The current approaches are expensive & minimally available, often involving high-end imaging such as MRI or even a highly invasive liver biopsy.

A common patient journey would be:

1. Clinician suspects liver disease and/or is screening for liver disease according to guidance and guideline documents like those from the American Association for the Study of Liver Disease (AASLD), the European Association for the Study of the Liver (EASL), the American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association (ADA).
2. Patient gets sent for blood tests; If suggestive of disease or equivocal, patient gets referred to a gastroenterologist (GI) or hepatologist.
3. Following a GI or hepatology visit; patients may get referred to radiology for imaging exams.
4. Following imaging, patients may get scheduled for a 3cm core liver biopsy.
5. Depending on the outcomes of up to 4+ different exams and 5+ clinical visits, patient is triaged for treatments and/or monitoring.

OnX facilitates early diagnosis of structural liver disease at point-of-care, which can - if caught early enough - be managed by the patients and their care teams outside of hospital settings and can even be reversed. There is currently no tool specifically designed and approved to screen for early-stage liver disease in a primary care setting.

Compared to available alternatives, OnX also offers the advantage of being fast, painless, non-invasive and with no radiation exposure. And this test, which can be completed and have data shared with the patient within the span of a single point-of-care clinical visit without the need for referrals or unnecessary second visits is a more clinically efficient solution for patients and their care teams alike.

Compared to Blood/Lab Tests

Standard liver function tests that measure the levels of certain enzymes and proteins in the blood are limited in their diagnosis of fibrosis, inflammation or cirrhosis. Other serum combination tests, while improved over standard liver enzyme tests for diagnosis of significant/advanced fibrosis and cirrhosis, have significant diagnostic limitations such as indeterminate values, low positive predictive values, and modest sensitivity and specificity.^{1 2}Liver blood tests have remained almost unchanged since they were developed in the 1950s, with the result being that many patients with liver disease are not identified until they have developed significant liver fibrosis.³Beyond not identifying significant disease, a separate population cohort study demonstrated that the majority of patients referred to hospital with abnormal liver tests do not have evidence of significant liver disease.⁴Compared to the current standard of care that is available in primary care or at point of care, OnX enhances the ability to detect structural liver disease at all stages and shows a significant improvement in accuracy over existing tools.

The OnX exam, which can be completed and have data shared with the patient within the span of a single clinical visit, offers several advantages even compared to the simplest blood or biomarker tests. For a blood panel, the patient needs to go to a blood draw lab or to a trained phlebotomist, wait for pathology to review and then the clinician to relay the findings (see Figure 1). Other types of specialty testing require even more steps, costs and friction for the patient, as well as clinical inefficiencies for the clinician. Patients benefit from being able to access an important diagnostic screening test at point of care, rather than being referred to a specialist or a centralized hospital system. This access and availability removes the friction of several appointments, traveling to referral centers, etc. for patients and decreases both direct and indirect costs (See Figure 1 below).

OnX Compared to Blood Tests for Liver Fibrosis
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Fibrosis Definition	OnX	NIS4⁵	FIB-4	NFS	ELF	BARD	APRI	FibroSURE
≥ F2/3/4	90 89.8	80	70⁶ 77-85⁷ 78⁸	66⁹	77¹⁰ 78-94¹¹ 80¹²	58¹³	74¹⁴ 71-80¹⁵ 86.6¹⁶ 79¹⁷	86¹⁸ 77¹⁹ 75-84²⁰ 72-90²¹
≥ F3/4	91 89.2	81	74²² 71²³ 80²⁴	68²⁵ 85²⁶	77²⁷ 90²⁸	62²⁹ 81³⁰	75³¹ 68³² 86.1³³	92³⁴ 81-88³⁵
≥ F4	94 89.3	NA	NA	NA	NA	NA	84.2³⁶	87³⁷ 94³⁸ 81-92³⁹ 75-92⁴⁰

Table 1: Area under the receiver operator curve (AUROC; in %) for classifying fibrosis as defined in the first column, comparing the OnX vs different blood tests.
AST = Aspartate Aminotransferase
ALT = Alanine Aminotransferase
NIS4 = Non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis
FIB-4 = Fibrosis 4
NFS = NAFLD Fibrosis Score
ELF = Enhanced Liver Fibrosis score
BARD = BMI, ALT, AST, Diabetes fibrosis score
APRI = AST to Platelet Ratio
Fibrotest/Fibrosure = biomarker test that uses the results of six blood serum tests to generate a score
NA = Not Available, as studies analyzed cohorts with advanced fibrosis (F3+F4) and not separately F4 alone.

Figure 1: The OnX improves the patient experience, makes tests more accessible, and establishes long-term clinical efficiencies by enabling front line physicians to easily perform tests in the clinic and/or at the bedside rather than needing to refer the patient elsewhere or transport to radiology.

Compared to FibroScan/Transient Elastography

In patients with known liver disease such as HBV/HCV or chronic alcoholism with outward signs of liver disease such as ascites or right upper quadrant (RUQ) pain, transient elastography is the most commonly applied technique to assess liver stiffness, an accepted correlate for fibrosis. Vibration controlled Transient Elastography (VCTE), available in some specialty hepatology clinics or hospital settings, is most commonly known as FibroScan in the U.S. FibroScan, made by Echosens, is a specialty blind ultrasound exam that uses pulse-echo sound wave acquisitions to measure liver stiffness in kilo-Pascals (kPa). This technique allows for a non-invasive assessment of liver stiffness, a physical parameter that has been correlated to fibrosis levels in bulk liver tissues. Stiffness is not only sensitive to fibrosis; it is also affected by various factors such as congestion, inflammation, and other factors.⁴¹Regardless, increased stiffness is abnormal and indicates liver disease that specially trained hepatologists and gastroenterologists can interpret based on other clinical indicators. FibroScan tests are most often ordered after a liver disease has been diagnosed via blood test or incidental finding, and the test is not yet approved by FDA or part of a standard of care for screening of patients and instead was cleared as a clinical decision support tool for patients with symptoms of liver disease.⁴²While this offers a widely accepted tool to aid in disease management, it is not standard of care to use this device for early-stage disease detection or screening and it is still uncommon to test for liver disease in patients with metabolic disorder, even though studies have demonstrated that widespread liver disease is often missed in patients with T2D.⁴³Furthermore, because it is limited to specialty care settings, it is typically reserved for patients who have most often progressed to symptomatic or later stage.

While prices vary depending on the model and the geographic area for the purchase, this large, cart-based system can cost over $300,000 USD in the US to purchase and requires bi-annual recalibration that costs >$10,000 USD. Due to these high costs, this is most often found in radiology departments in hospitals and at specialty hepatology clinics in hospital settings. Additionally, it is difficult, and often impossible to measure inflammation itself using this bulk measurement method.

Other types of ultrasound elastography solutions, such as shearwave elastography that be an add on to radiology grade ultrasound system and the newer hepatology versions of this including the Velacur by SonicIncytes, offer more of the same issues and concerns from a technological and clinical perspective. The Velacur does stand apart as it is designed as a hepatology tool and not for radiology or hospital systems, but this technically is elastography and is an expensive system, prone to the same issues and concerns and not poised at all to denote liver inflammation.

Compared to MRE

A Magnetic Imaging Resonance Elastography test can only be performed on suitably equipped MRI machines making these tests not widely available, accessible or affordable for patients and not appropriate for more moderate disease diagnoses. MRE does provide a more advanced diagnosis in patients suspected of disease and but is limited in the scope of providing surveillance of high-risk patient populations. While ongoing work is looking at MRE for evaluating liver disease at high-end centers such as the Mayo Clinic where MRE was first developed, this modality is not commonly available or utilized for early disease surveillance and the test is not yet approved by FDA for screening and it is not part of a standard of care for screening.⁴⁴

Compared to Biopsy

Liver biopsies are only centrally available and must be performed by a trained hepatologist or interventional radiologist. Biopsies are invasive and pose risks for patients. Minor complications include pain at the biopsy site or vasovagal episodes.⁴⁵The most commonly reported and concerning major complication is bleeding, occurring in 0.8-1.7% of liver biopsies.⁴⁶ Although death is rare, ranging from 0% to 0.14%⁴⁷ , higher rate (0.33%) was reported in one study.⁴⁸The complication risk is presumed to be higher in patients with advanced liver disease. Often several “core” samples are required and the exam can be lengthy. After the biopsy or biopsies are completed, patients need to be monitored for a few hours, and may also require a person to accompany them home. Biopsy is not an acceptable option for all patients, and because of its risks, is usually reserved fora relatively limited number of patients for diagnosis and assessment of liver disease severity. While this is considered the gold standard for liver diagnostics, it is not a practical early detection tool for use at point of care.

Market Need:

The general market need for liver diagnostics is considered a top priority by WHO and many global healthcare groups as liver disease is one of the fastest growing causes of morbidity and mortality worldwide. Screening for MASLD in patients with risk factors is now called for in industry guidance and guideline documents from the AASLD, AACE and ADA as well as EASL and other European and international health groups.

Standard of Care Significantly Delays Diagnosis

The current standard of care for detecting liver disease is to wait until outward symptoms appear either via elevated liver function tests (LFTs) or other physical exam findings that include jaundice, spider angioma, a nodular liver on palpation, splenomegaly, ascites, caput medusae, palmar erythema, gynecomastia, and asterixis.⁴⁹LFTs present a significant challenge since these tests can be normal even in patients with chronic hepatitis or cirrhosis.⁵⁰Outward physical exam findings are most often only present when liver disease and resultant disease has advanced to near end stage.⁸⁴

While the current standard of care results in diagnosis only when outward symptoms appear or an incidental finding reveals silent disease, structural liver disease detection and staging can be an early indication that a chronic liver disease (CLD) exists in asymptomatic patients.

Related to screening and diagnosis for liver inflammation, public health studies evaluating screening for liver fibrosis in selected populations with risk factors for MASLD and alcoholic liver disease have demonstrated significant findings of early fibrosis and later stage liver disease, indicating that significant amounts of disease are currently missed via the current standard of care. A large study of 1918 patients with type 2 diabetes - a serious risk factor for MASLD - using a transient elastography device, the FibroScan, and subsequent liver biopsy, showed the prevalence of fibrosis stage ≥F3 was 18% (based on liver stiffness >9.6 kPa, suggestive of stage ≥F3 in this patient set). Of the approximately one-third of patients who underwent a subsequent liver biopsy, 56% had steatohepatitis, 21% had advanced fibrosis, and 29% had cirrhosis. The researchers concluded that their data support screening for NAFLD/MASLD and/or advanced fibrosis in patients with Type 2 Diabetes (T2D).⁵¹ Other studies support this finding and the call for fibrosis screening in patients with T2D.⁵²

Another large-scale study from the UK seeking to assess high risk patients used transient elastography (TE) to screen for liver fibrosis in patients fulfilling one or more selected risk factors for developing chronic liver disease: (1) excessive alcohol use, (2) T2D or (3) persistently elevated alanine aminotransferase (ALT) liver function enzyme with negative serology. Of the 378 patients assessed by TE, 27% had increased liver stiffness (>8 kPa). Significantly, most patients (72.4%) with moderate-to-severe liver fibrosis or cirrhosis had normal liver enzymes, indicating that the diagnosis of chronic liver disease would have been missed if patients had been assessed only with the standard diagnostic tests used in primary care.⁵³

While these and other studies suggest benefit of screening for liver disease in high-risk populations, the only available tests for screening in primary care, include physical exams, blood tests, and less prevalent are new combination serum tests and biomarkers. As noted, physical symptoms are usually only present in advanced stages of cirrhosis. Blood tests and new blood based biomarkers have been shown to be somewhat useful in the exclusion of advanced fibrosis and cirrhosis, they do not detect early fibrosis nor are they ideal to differentiate between early to intermediate stages of fibrosis where treatment recommendations might be very different.⁵⁴ Nor do they differentiate between fibrosis stages, or correlate with either transient or persistent liver inflammation. A large University of Illinois retrospective observational study on 771 liver biopsies was conducted for evaluating common serum and blood tests and clearly showed that laboratory values correlate poorly with liver disease. These researchers concluded in 2018 that, “The health care burden from chronic liver disease (CLD) will likely continue to rise, unless clinicians are made aware that normal or near normal laboratory findings may be seen in asymptomatic patients. Earlier identification of asymptomatic patients will allow for treatment with new promising modalities and decrease morbidity and mortality from CLD.”⁵⁵As noted above, the OnX solution can provide up to 64% improvement over existing screening tools with respect to the AUC of detection of disease, particularly in earlier stages.

Effective Liver Screening Should Begin at Point of Care

Early diagnosis and non-invasive detection of significant stage liver disease are important for reducing further disease progression toward severe clinical consequences.⁵⁶In addition to the above cited studies, several guidelines and leading organizations have begun calling for regular screening for liver disease by PCPs especially in populations with prior or current diagnosed liver disease or the aforementioned known risk factors such as excessive alcohol use, obesity, metabolic disorder, and diabetes.⁵⁷

While patients with confirmed liver disease or suspected of having liver disease due to an abnormal blood test or incidental finding can be referred to specialists for additional diagnostics (i.e. FibroScan in Hepatology or MRI in Radiology), OnX would represent the first point-of-care diagnostic tool for primary care and other front line clinicians (i.e. endocrinologists) to accurately determine liver health and - if needed - refer their patients to specialists according to these findings.

Figure 2: Stage Shift in Liver Disease Detection

LIVER DISEASE IS OFTEN UNDIAGNOSED		MANY PATIENTS ARE DIAGNOSED TOO LATE WITH SYMPTOMS
A prospective screening study of T2D patients without any known liver disease, 7.1% had undiagnosed advanced fibrosis.⁵⁸		Cirrhosis was unrecognized until the development of HCC in 64% of patients with a clear indication for screening.⁶⁴
A large prospective study recruited 1118 patients in the primary setting with incidental abnormal LFTs and found undiagnosed advanced fibrosis in 7.6% of patients.⁵⁹		Only 1 in 3 people with cirrhosis know that they have it.⁶⁵
A meta-analysis of patients with T2D found that 35.54% had clinically significant fibrosis and 14.95% had advanced fibrosis.⁶⁰		In a US population-based study, MASLD/NAFLD was the most common underlying etiologic risk factor for HCC (59%), and increases with advances in liver disease.⁶⁶
A retrospective study showed that 63.9% of patients undergoing pancreaticoduodenectomy had undiagnosed liver fibrosis.⁶¹		Cirrhosis is the 12th leading cause of death in the United States.⁶⁷
Fibrosis is significantly underdiagnosed by diabetes specialists.⁶²
Widespread liver disease is missed in patients with T2D.⁶³

Table 2: Early stage disease is frequently undiagnosed, leading to stage shift and excess morbidity/mortality.

Early detection of liver disease in high-risk populations can serve as an indicator of overall liver health and underlying chronic liver disease progression.⁶⁸In order to minimize liver disease-related complications such as cirrhosis, cancer, transplant or death, increasing numbers of key-opinion leaders (KOL) have repeatedly called for early disease detection, screening and continuous monitoring outside of hepatology, within relevant subspecialties (i.e. endocrinology and cardiology) or in primary care.⁶⁹ As such, given the high prevalence and resulting mortality of cirrhosis, liver diseases should be detected, characterized and monitored in early stages in high-risk populations, when possible.

The OnX solution is a unique and novel solution that improves and expands liver disease detection to point-of-care/primary care, and this early detection has the potential to improve patient outcomes.

As noted above, the OnX has been widely introduced and has demonstrated product/market fit and market demand. Initial target markets include GI/hepatology practices in both private practices and large hospital networks, as the market needs non-invasive diagnostic tools to advance treatments for liver and GI conditions. There are ~16,000 GI/hepatologists in North America that could use this tool today in their practice. Further, due to the bidirectional relationship between diabetes and MASLD, we address endocrinology, metabolic and obesity clinics who need a liver metric for risk calculations since liver health is directly correlated to microvascular, macrovascular and cardiovascular outcomes. With over 600,000 primary care, ED, and hospitalists in North America that cater to people seeking routine and urgent medical attention, these are eventual end targets as these settings are the first line of defense for early detection and management of liver disease.

Oncoustics already has quotes, testimonials and endorsements from hepatologists, radiologists, endocrinologist and primary care physicians all supporting the need and desires to be able to perform point of care liver screening for their patients. By advancing this platform and expanding the usefulness of liver diagnostics to include liver inflammation, MASH/NASH and HCC, we would dramatically expand the interest and demand for these point of care tools.
‍

Clinical Testimonials and Support for Oncoustics:

A point of care liver dx solution that provides a rapid bedside exam and yields information on liver fibrosis, steatosis, inflammation and nodule formation, could hugely impact the field of hepatology. This could provide upstream liver surveillance to combat the growth of liver diseases such as fatty liver which is expected to result in serious morbidity and mortality due to cirrhosis and liver cancer, over the next two decades.

Samuel S. Lee, MD, FRCPC, FAASLD
Professor of Medicine (Hepatology)
University of Calgary, Canada

As a primary care physician, I have the tools to screen my patients with diabetes for high-risk end organ damage, including cardiovascular risk, retinopathy, nephropathy, and neuropathy. A tool to screen for NASH/NAFLD is equally important, and I love that the OnX would allow me to screen and counsel the patient within a single encounter.

Matthew Sakumoto, MD, CIMO
University of California SF, Sutter Health

“Nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and is recognized as the most prevalent chronic liver disease in the world. In the United States, NAFDL affects up to 30% of the population today. The team at Oncoustics are developing a reliable and portable screening and surveillance device for healthcare providers to optimize ‘Precision Medicine’ in a highly individualized approach.”

Aijaz Ahmed, MD
Hepatologist at Stanford Medicine

[Oncoustics’ technique] makes perfect sense to me as the raw data is much richer than that in current medical images…This technique is much easier to use and would benefit millions of at risk patients.

Dr. Chen Fong, MD
Prior Chair of Radiology, University of Calgary, Canada

“The Oncoustics’ technology broadens our options and could be performed in the clinic or in an outpatient center. As applications and strategies evolve, there is huge potential for enhanced, non-invasive tissue characterization, enhanced histopathology and the likelihood for optimization of clinical workflow along with advancing diagnostic accuracy of liver or prostate biopsies.”

Anand Patel, MD
University of California SF, Providence Healthcare, CA
Medical Director, RNDR Care

A large proportion of the patients cared for by endocrinologists and diabetologists have fatty liver disease. The biggest challenge we face is in identifying whom amongst those many patients have advanced fibrosis and are at risk for liver failure. If we had a simple tool to assist us in identifying that subgroup of patients we would know whom to refer to hepatology for specialty care and potentially for treatment with therapies currently being tested for the treatment of NAFLD. Point of care tools would be particularly useful in this respect.

Gary F. Lewis, MD, FRCP(C)
Banting and Best Diabetes Centre, University of Toronto, Canada

End Notes

¹ Karanjia RN, CrosseyMME, Cox IJ, et al. Hepatic steatosis and fibrosis: {Non}-invasive assessment. WorldJ Gastroenterol. 2016;22(45):9880-9897. doi:10.3748/wjg.v22.i45.9880

² Patel K, Sebastiani G.Limitations of non-invasive tests for assessment of liver fibrosis. JHEPreports Innov Hepatol. 2020;2(2):100067. doi:10.1016/j.jhepr.2020.100067

³ Williams R, Aspinall R,Bellis M, et al. Addressing liver disease in the UK: A blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis. Lancet.2014;384(9958):1953-1997. doi:10.1016/S0140-6736(14)61838-9

⁴ Donnan PT, McLernon D,Dillon JF, et al. Development of a decision support tool for primary care management of patients with abnormal liver function tests without clinically apparent liver disease: A record-linkage population cohort study and decision analysis (ALFIE). Health Technol Assess (Rockv). 2009;13(25).doi:10.3310/hta13250

⁵ Harrison SA, Ratziu V,Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol.2020;5(11):970-985. doi:10.1016/S2468-1253(20)30252-1

⁶Harrison SA, Ratziu V, Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol. 2020;5(11):970-985.doi:10.1016/S2468-1253(20)30252-1

⁷ Patel PJ, Connoley D,Rhodes F, Srivastava A, Rosenberg W. A review of the clinical utility of theEnhanced Liver Fibrosis test in multiple aetiologies of chronic liver disease. AnnClin Biochem. 2020;57(1):36-43. doi:10.1177/0004563219879962

⁸ Corporate MedicalPolicy Origination: Last CAP Review: Next CAP Review: Last Review. Published online 2021.

⁹Harrison SA, Ratziu V,Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol.2020;5(11):970-985. doi:10.1016/S2468-1253(20)30252-1

¹⁰Harrison SA, Ratziu V,Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol.2020;5(11):970-985. doi:10.1016/S2468-1253(20)30252-1

¹¹Patel PJ, Connoley D,Rhodes F, Srivastava A, Rosenberg W. A review of the clinical utility of theEnhanced Liver Fibrosis test in multiple aetiologies of chronic liver disease. Ann Clin Biochem. 2020;57(1):36-43. doi:10.1177/0004563219879962

¹²Corporate MedicalPolicy Origination: Last CAP Review: Next CAP Review: Last Review. Published online 2021.

¹³Harrison SA, Ratziu V,Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol.2020;5(11):970-985. doi:10.1016/S2468-1253(20)30252-1

¹⁴ Harrison SA, Ratziu V,Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol.2020;5(11):970-985. doi:10.1016/S2468-1253(20)30252-1

¹⁵ Patel PJ, Connoley D,Rhodes F, Srivastava A, Rosenberg W. A review of the clinical utility of the Enhanced Liver Fibrosis test in multiple aetiologies of chronic liver disease. Ann Clin Biochem. 2020;57(1):36-43. doi:10.1177/0004563219879962

¹⁶ Han MAT. Noninvasive tests (Nits) for hepatic fibrosis in fatty liver syndrome. Life.2020;10(9):1-16. doi:10.3390/life10090198

¹⁷Corporate MedicalPolicy Origination: Last CAP Review: Next CAP Review: Last Review. Published online 2021.

¹⁸Cheah MCC, McCullough AJ, Goh GBB. Current modalities of fibrosis assessment in non-alcoholic fatty liver disease. J Clin Transl Hepatol. 2017;5(3):261-271.doi:10.14218/JCTH.2017.00009

¹⁹Corporate MedicalPolicy Origination: Last CAP Review: Next CAP Review: Last Review. Publishedonline 2021.

²⁰ Lab ManagementGuidelines FibroTest/FibroSURE. Published online 2019. Accessed July 13, 2021.www.eviCore.com

²¹Lab ManagementGuidelines FibroTest/FibroSURE. Published online 2019. Accessed July 13, 2021. www.eviCore.com

²²Harrison SA, Ratziu V,Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol.2020;5(11):970-985. doi:10.1016/S2468-1253(20)30252-1

²³Schmoyer CJ, Kumar D,Gupta G, Sterling RK. Diagnostic Accuracy of Noninvasive Tests to DetectAdvanced Hepatic Fibrosis in Patients With Hepatitis C and End-Stage RenalDisease. Clin Gastroenterol Hepatol. 2020;18(10):2332-2339.e1.doi:10.1016/j.cgh.2020.02.019

²⁴ Cheah MCC, McCullough AJ, Goh GBB. Current modalities of fibrosis assessment in non-alcoholic fatty liver disease. J Clin Transl Hepatol. 2017;5(3):261-271.doi:10.14218/JCTH.2017.00009

²⁵ Harrison SA, Ratziu V,Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol.2020;5(11):970-985. doi:10.1016/S2468-1253(20)30252-1

²⁶Cheah MCC, McCullough AJ, Goh GBB. Current modalities of fibrosis assessment in non-alcoholic fatty liver disease. J Clin Transl Hepatol. 2017;5(3):261-271.doi:10.14218/JCTH.2017.00009

²⁷ Harrison SA, Ratziu V,Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospectivederivation and global validation study. Lancet Gastroenterol Hepatol.2020;5(11):970-985. doi:10.1016/S2468-1253(20)30252-1

²⁸Cheah MCC, McCulloughAJ, Goh GBB. Current modalities of fibrosis assessment in non-alcoholic fatty liver disease. J Clin Transl Hepatol. 2017;5(3):261-271.doi:10.14218/JCTH.2017.00009

²⁹Harrison SA, Ratziu V,Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol.2020;5(11):970-985. doi:10.1016/S2468-1253(20)30252-1

³⁰ Cheah MCC, McCullough AJ, Goh GBB. Current modalities of fibrosis assessment in non-alcoholic fatty liver disease. J Clin Transl Hepatol. 2017;5(3):261-271.doi:10.14218/JCTH.2017.00009

³¹ Harrison SA, Ratziu V,Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol.2020;5(11):970-985. doi:10.1016/S2468-1253(20)30252-1

³² Schmoyer CJ, Kumar D,Gupta G, Sterling RK. Diagnostic Accuracy of Noninvasive Tests to DetectAdvanced Hepatic Fibrosis in Patients With Hepatitis C and End-Stage Renal Disease. Clin Gastroenterol Hepatol. 2020;18(10):2332-2339.e1.doi:10.1016/j.cgh.2020.02.019

³³Han MAT. Noninvasivetests (Nits) for hepatic fibrosis in fatty liver syndrome. Life.2020;10(9):1-16. doi:10.3390/life10090198

³⁴ Cheah MCC, McCullough AJ, Goh GBB. Current modalities of fibrosis assessment in non-alcoholic fatty liver disease. J Clin Transl Hepatol. 2017;5(3):261-271.doi:10.14218/JCTH.2017.00009

³⁵ Han MAT. Noninvasivetests (Nits) for hepatic fibrosis in fatty liver syndrome. Life.2020;10(9):1-16. doi:10.3390/life10090198

³⁶Han MAT. Noninvasivetests (Nits) for hepatic fibrosis in fatty liver syndrome. Life.2020;10(9):1-16. doi:10.3390/life10090198

³⁷Salkic NN, Jovanovic P,Hauser G, Brcic M. Fibro test/fibrosure for significant liver fibrosis and cirrhosis in chronic hepatitis B: A meta-analysis. Am J Gastroenterol.2014;109(6):796-809. doi:10.1038/ajg.2014.21

³⁸ Han MAT. Noninvasive tests (Nits) for hepatic fibrosis in fatty liver syndrome. Life.2020;10(9):1-16. doi:10.3390/life10090198

³⁹Lab ManagementGuidelines FibroTest/FibroSURE. Published online 2019. Accessed July 13, 2021.www.eviCore.com

⁴⁰Lab ManagementGuidelines FibroTest/FibroSURE. Published online 2019. Accessed July 13, 2021.www.eviCore.com

⁴¹Shen F, Mi Y-Q, Xu L,et al. Moderate to severe hepatic steatosis leads to overestimation of liver stiffness measurement in chronic hepatitis {B} patients without significant fibrosis. Aliment Pharmacol \& Ther. 2019;50(1):93-102.doi:10.1111/apt.15298

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