Barriers and facilitators to liver fibrosis screening: Perspectives and practices of Canadian primary care physicians

Abstract

Background:

Metabolic dysfunction–associated steatotic liver disease (MASLD) is highly prevalent, yet primary care physicians (PCPs) face barriers to identifying and referring high-risk individuals. We surveyed Canadian PCPs to identify barriers and facilitators to MASLD-related fibrosis screening.

Methods:

A multidisciplinary team developed a 38-item online survey with multiple-choice and Likert scale questions to assess PCPs’ MASLD knowledge and barriers and facilitators to screening. The survey was distributed anonymously in April–August 2024.

Results:

Seventy-one participants completed the survey. One in five rated their MASLD diagnostic knowledge as very or extremely familiar, whereas a quarter reported little to no knowledge. Although >90% correctly identified obesity, type 2 diabetes, and dyslipidemia as risk factors, only 54% screened these populations. Among those who screened, 55% used FIB-4 and 29% transient elastography, while the most common tools were ultrasound (74%) and alanine aminotransferase (71%). Overall, 96% reported at least one barrier, including time limitations, resource constraints, and limited access to tools. Barriers also varied by province; PCPs in Alberta reported fewer access issues with tools like FIB-4 than those in other provinces, including Ontario and Quebec. Encouragingly, over 80% expressed willingness to adopt integrated guidelines and automated risk tools into their practice.

Conclusions:

Despite awareness of MASLD risk factors among Canadian PCPs, substantial gaps remain in screening due to limited knowledge, inconsistent tool use, and systemic barriers. These findings highlight the need for a coordinated national strategy to support PCPs in the early identification and referral of patients at risk for MASLD-related fibrosis.

Lay Summary

Metabolic dysfunction–associated steatotic liver disease (MASLD), is now the most common chronic liver disease in the world. If it is not diagnosed early, it can lead to serious problems like liver scarring (fibrosis), liver failure, and even liver cancer. Family doctors, also known as primary care physicians (PCPs), play a big role in spotting early signs of MASLD and sending patients for further care. But we do not know what helps them screen their patients in everyday practice or what prevents them from doing so. To learn more, we surveyed family doctors across Canada between April and August 2024. We received 71 responses from seven provinces. Our results showed that while many doctors knew that people with obesity and type 2 diabetes are at higher risk for MASLD, only about half were screening these patients. Even when they did screen, they often used tools like ultrasound and standard blood tests, which are not very good at detecting liver scarring. Lack of knowledge was not the only issue. Almost all doctors said they faced other challenges, such as insufficient time or unclear screening guidelines. On a positive note, most were open to using new tools, such as automated systems to flag high-risk patients and easy-to-follow guidelines, to aid in screening. Our study found that Canadian family doctors face many challenges in screening for liver disease, but they're willing to use better tools and supports. To improve early detection and care, Canada needs a national plan that includes better guidelines, innovative tools in electronic records, and ongoing training for doctors and other health care professionals, such as nurses.

Introduction

Metabolic dysfunction–associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD) (1), is the most prevalent chronic liver disease worldwide (2). The natural history of MASLD is complex, marked by slow, often asymptomatic progression from steatosis to reversible metabolic dysfunction–associated steatohepatitis (MASH). But if left untreated, MASLD can advance to irreversible end-stage liver cirrhosis and hepatocellular carcinoma (HCC) (2,3).

One in three Canadian adults is estimated to have MASLD (4). A recent national estimate using the Canadian Health Measures Survey estimated that between a third to half of Canadian adults have hepatic steatosis, and between 195,000 and 406,200 are at high risk of advanced liver fibrosis (5). Notably, MASLD disproportionately affects people with type 2 diabetes mellitus (T2DM)—with a global prevalence between 60% and 86% (6)—where the synergistic relationship between the two metabolic diseases results in significantly faster progression toward advanced liver disease (7). Yet, despite MASLD being projected to cause 75% of all new cirrhosis diagnoses by 2040 and, subsequently, an estimated CAD $5 billion in health care costs by 2050, system barriers to screening persist across Canada (8–11).

The 2024 guidelines by the European Associations for the Study of the Liver, Obesity and Diabetes (EASL, EASO, EASD) (12), the American Diabetes Association's (ADA) 2025 guidelines (13,14), the 2025 ADA consensus report (15), and the 2023 American Association for the Study of Liver Diseases (AASLD) guidelines (16) all continue to recommend screening for fibrosis in high-risk populations. Starting in 2016, these international agencies began recommending the use of a simple, non-invasive risk score known as the Fibrosis-4 index (FIB-4) to implement first-line screening practices (8,12–16).

However, there are no Canadian national guidelines for liver fibrosis screening at the time of writing (17,18). Primary care physicians (PCPs) face an increasing number of patients at risk of liver fibrosis and are the gatekeepers to patient referrals to specialists. Previous studies have concluded that initial screening by PCPs is likely a cost-effective and convenient strategy (19–22). Evidence supports screening high-risk populations for advanced liver fibrosis using non-invasive tests, yet clinical practice remains substandard in Canada (8,23,24). To that end, the present study aims to examine the current MASLD-related fibrosis screening practices of PCPs across Canada and to identify barriers and facilitators that can enhance screening.

Methods

Survey design

We conducted a cross-sectional online survey of Canadian PCPs using Qualtrics (Seattle, Washington). The survey aimed to assess PCPs’ knowledge of MASLD/MASH and the screening pathways for MASLD-related fibrosis based on existing surveys (25–28). The survey consisted of 38 items across five domains: (1) demographic characteristics, (2) knowledge of MASLD, (3) clinical care pathway of MASLD-related fibrosis screening, (4) barriers to MASLD-related fibrosis screening, and (5) facilitators to MASLD-related fibrosis screening (Online Supplemental File #1). Items were multiple-choice questions or rated on a Likert scale, with either single- or multiple-select options.

A multidisciplinary team, including two hepatologists, one endocrinologist, two PCPs, one nurse, two epidemiologists, and one patient representative, discussed and finalized the survey questions, with particular focus on the barriers and facilitators so that real-world challenges and practical supports were reflected. The team piloted and iteratively revised the survey to ensure the questions were well understood and the survey logic was functional before distribution.

Recruitment

Eligible participants were PCPs practising in Canada. Survey invitations were distributed via email to PCPs who were Canadian members of MDBriefCase. MDBriefCase provides accredited, online continuing professional development free of charge to more than 280,000 members in Canada, Australia, Africa, and the Middle East. Specifically, all Canadian members are vetted to ensure they are licensed Canadian physicians, and lists are actively monitored to ensure accuracy. Approximately 26,000 Canadian PCPs who opted in to receive communications were sent an email to participate. Additional recruitment occurred via social media platforms (Facebook and X, formerly Twitter) associated with the Fatty Liver Alliance, MDBriefCase, and the principal investigators. All responses were anonymous. No direct incentives were offered for participation. Survey responses were collected from April 23 to August 31, 2024. The study was approved by the Queen's University Research Ethics Board, Canada (#6041010, 2024).

Data analysis

Descriptive statistics were used to report response frequencies; χ² tests were used to assess differences in the proportion of PCPs experiencing barriers to each screening tool by province or territory. Statistical analyses were conducted using IBM SPSS Statistics (Version 29.0.2.0).

Results

Sample characteristics

A total of 71 PCPs completed the survey, with a median completion time of 6 minutes and 42 seconds. Demographic characteristics of the surveyed PCPs are summarized in Table 1. Respondents were evenly split by gender. A majority of participants were aged 46 years or older (80.2%), with 73.2% having been in practice for over 20 years. Responses were collected across seven provinces and territories, mainly Ontario (47.9%), Alberta (22.5%), and Quebec (12.7%). More than half of respondents practised in community clinics (54.9%), and most served large urban areas with populations over 500,000 people (54.9%); 78.9% reported working within a multidisciplinary team, commonly with other PCPs, nurses, dietitians, social workers, and pharmacists. Academic institution affiliation was reported by 49.3% of respondents. Physicians estimated that the proportion of their patients with known or suspected MASLD was lower than national prevalence estimates: 83.1% estimated that MASLD affected ≤30% of their practice population.

Table 1:

Demographic characteristics of surveyed primary care physicians (n = 71)

Characteristics	No. (%)
Gender
Male	35 (49.3)
Female	35 (49.3)
Prefer not to say	1 (1.4)
Age
<35	4 (5.6)
36–45	10 (14.1)
46–55	17 (23.9)
56–65	17 (23.9)
66–75	20 (28.2)
>75	3 (4.2)
Years of practice
<5	2 (2.8)
5–10	10 (14.1)
10–20	7 (9.9)
>20	52 (73.2)
Province/territory of primary practice
Ontario	34 (47.9)
Alberta	16 (22.5)
Quebec	9 (12.7)
British Columbia	7 (9.9)
Manitoba	3 (4.2)
Saskatchewan	1 (1.4)
Northwest Territories	1 (1.4)
Practice location
Community clinic	39 (54.9)
Private clinic	32 (45.1)
Practice setting
Rural area	4 (5.6)
Mix rural/small urban (pop. 10,000–100,000)	8 (11.3)
Small urban area (pop. 100,001–200,000)	11 (15.5)
Medium urban area (pop. 200,001–500,000)	9 (12.7)
Large urban area (pop. >500,000)	39 (54.9)
Presence of multidisciplinary team in clinic
No	15 (21.1)
Yes, with …	56 (78.9)
Other primary care practitioner(s)	48 (67.6)
Nurse(s)	39 (54.9)
Dietitian(s)/nutritionist(s)	23 (32.4)
Social worker(s)	22 (31.0)
Pharmacist(s)	20 (28.2)
Counsellor(s)/therapists(s)	18 (25.4)
Specialist(s)	17 (23.9)
Physiotherapist(s)	9 (12.7)
Case manager(s)	3 (4.2)
Personal affiliation with academic institution
No	36 (50.7)
Yes	35 (49.3)

PCP knowledge of MASLD

Among those surveyed, 18.3% self-rated their knowledge of MASLD/MASH diagnosis as “very” or “extremely” familiar, 46.5% “moderately” familiar, while 35.2% indicated little to no familiarity; 59.2% indicated that they were aware of the updated nomenclature for NAFLD/NASH to MASLD/MASH. However, only 22.5% reported they were aware that having MASLD and increased alcohol intake is defined as metabolic and alcohol–associated liver disease (MetALD). The most commonly recognized high-risk groups for MASLD were patients with obesity (100%), T2DM (97.2%), and dyslipidemia (91.5%), whereas hypertension (43.7%) remained under-identified (Figure 1A).

Figure 1: A) Proportion of Canadian primary care physicians who classify each condition as high-risk for MASLD-related fibrosis (n = 71); B), among those who actively screen for MASLD-related fibrosis (n = 38), the proportion who report screening the high-risk population group.

MASLD = Metabolic dysfunction–associated steatotic liver disease

MASLD-related fibrosis screening practices

Of the 71 surveyed PCPs, only 53.5% screened for MASLD-related liver fibrosis in their practice. Among PCPs who screened for MASLD-related liver fibrosis (n = 38), screening was most frequently targeted at patients with obesity (97.4%) and T2DM (94.7%) (Figure 1B). Use of guideline-recommended, non-invasive fibrosis screening tests, such as FIB-4 (55.3%), transient elastography (FibroScan) (28.9%), and FibroTest (15.8%), remained relatively uncommon (Figure 2). Instead, most PCPs relied on alanine aminotransferase (ALT) (71.1%) and ultrasound (76.3%) as first-line screening tools.

Figure 2: Proportion of Canadian primary care physicians who reported using specific first-line biomarkers and liver assessment tools to screen for MASLD-related liver fibrosis (n = 38).

ALT = Alanine aminotransferase; APRI = AST to platelet ratio index; AST = Aspartate aminotransferase; ELF score = Enhanced liver fibrosis score; FIB-4 = Fibrosis-4 score; MASLD = Metabolic dysfunction–associated steatotic liver disease; MRE = Magnetic resonance elastography; NFS = Non-alcoholic fatty liver disease (NAFLD) fibrosis score; pSWE = Point shear wave elastography

Knowledge of MASLD/MASH guidelines

Among surveyed PCPs, 87.3% reported that MASLD/MASH guideline updates were typically learned through scientific venues (eg, conferences, continuing medical education, or academic papers); 50.7% cited professional emails or websites (eg, Diabetes Canada), 40.8% point-of-care resources (ie, UpToDate), and 33.8% word of mouth. Only 36.6% knew that MASLD/MASH clinical pathways existed, and only 23.9% (17) followed a formal care pathway in their clinical work. Of those who followed a clinical care pathway for MASLD/MASH (17), 47.1% followed the Calgary/Alberta pathway, 17.6% American Association of Clinical Endocrinology's (AACE's) guidelines, 17.6% ADA guidelines, 17.6% an internal guideline, and 11.8% American Gastroenterological Association (AGA) NAFLD clinical care pathway.

Barriers to MASLD-related fibrosis screening

PCPs reported several barriers to screening for MASLD-related liver fibrosis (Figure 3). Overall, 95.8% identified at least one barrier to fibrosis screening and 83.1% marked two or more. The most cited challenges included limited time and resources to screen (49.3%), limited treatment options (43.7%), and lack of available screening tools (40.8%).

Figure 3: Proportion of primary care physicians that reported specific barriers to MASLD-related liver fibrosis screening in primary care (n = 71).

MASLD = Metabolic dysfunction–associated steatotic liver disease

Physicians also described encountering barriers to using specific screening tools. Barriers to commercial tests were most frequently cited for FibroTest (59.2%), FibroMeter (54.9%), and the ELF (enhanced liver fibrosis) score (53.5%), followed by FIB-4 (47.9%; 34), and aspartate aminotransferase (AST) (33.8%). For imaging tests, barriers to accessing transient elastography (66.2%), point shear wave elastography (pSWE) (59.2%), and magnetic resonance elastography (MRE) (54.9%) were most frequently reported. Notably, barriers to specific screening tools varied by province/territory and practice setting. Physicians in Ontario and British Columbia reported the most barriers, while PCPs from Alberta reported significantly fewer barriers to accessing FIB-4, FibroTest, ELF, FibroMeter, FibroScan, pSWE, and MRE compared to other regions (Online Supplemental File #2, Tables 1 and 2). Furthermore, PCPs in non-large urban areas (population of <500,000) reported significantly more barriers to accessing ALT, FibroTest, ELF, FibroMeter, FibroScan, pSWE, and MRE, compared to those in large urban areas (Online Supplemental File #2, Tables 3 and 4).

Reasons for these barriers (Table 2) include limited availability of advanced biomarker and imaging tests, such as FibroTest (25.4%), FibroMeter (19.7%), ELF (15.5%), transient elastography (32.4%), pSWE (19.7%), and MRE (21.1%). Additionally, lack of reimbursement or the requirement for patients to pay out of pocket for specific tests were also reported, particularly for AST (18.3%), FibroTest (8.5%), and transient elastography (9.9%).

Table 2:

Reported barriers to specific MASLD-related liver fibrosis screening tools in primary care (n = 71)

		No. (%) of patients
Screening tool	Recommended for MASLD-related liver fibrosis screening?	Not reimbursed (patients pay out of pocket)	Not readily available to me	Unsatisfactory accuracy	Unaware of this screening tool	Unsure how to interpret results	Long wait time
FIB-4	Yes	4 (5.6)	12 (16.9)	0 (0.0)	12 (16.9)	10 (14.1)	1 (1.4)
FibroTest	Yes	6 (8.5)	18 (25.4)	0 (0.0)	17 (23.9)	11 (15.5)	2 (2.8)
ELF score	Yes	0 (0.0)	11 (15.5)	0 (0.0)	24 (33.8)	7 (9.9)	0 (0.0)
FibroMeter	Yes	0 (0.0)	14 (19.7)	0 (0.0)	23 (32.4)	7 (9.9)	0 (0.0)
ALT	No	3 (4.2)	0 (0.0)	1 (1.4)	2 (2.8)	2 (2.8)	0 (0.0)
AST	No	13 (18.3)	2 (2.8)	1 (1.4)	3 (4.2)	2 (2.8)	0 (0.0)
Transient elastography (FibroScan)	Yes	7 (9.9)	23 (32.4)	0 (0.0)	7 (9.9)	7 (9.9)	5 (7.0)
pSWE	Yes	1 (1.4)	14 (19.7)	0 (0.0)	24 (33.8)	7 (9.9)	1 (1.4)
MRE	Yes	1 (1.4)	15 (21.1)	0 (0.0)	23 (32.4)	6 (8.5)	1 (1.4)
Ultrasound	No	0 (0.0)	0 (0.0)	1 (1.4)	2 (2.8)	1 (1.4)	8 (11.3)

MASLD = Metabolic dysfunction–associated steatotic liver disease; FIB-4 = Fibrosis-4 score; ELF score = Enhanced Liver Fibrosis Score; ALT = Alanine aminotransferase; AST = Aspartate aminotransferase; pSWE = Point shear wave elastography; MRE = Magnetic resonance elastography

Facilitators of MASLD/MASH screening

A minority of respondents reported having practical supports for MASLD/MASH screening in their practice (Figure 4): 38.0% reported collaboration with hepatology/gastroenterology (GI), 32.4% collaboration with endocrinology, 29.6% collaboration with obesity specialists, 26.8% integrated clinical care pathways through the electronic medical records (EMR), and 25.4% automated FIB-4 calculation followed by risk stratification. Among those without the aforementioned facilitators in their practice, a majority stated willingness to adopt these supports: 80.8% for integrated clinical care pathways via EMR, 84.9% automated FIB-4 calculation, 88.6% collaboration with hepatology/GI, 89.6% endocrinology, and 90.0% obesity specialists.

Figure 4: Presence and acceptability of facilitators to MASLD-related liver fibrosis screening in primary care practices (n = 71).

MASLD = Metabolic dysfunction–associated steatotic liver disease; EMR = Electronic medical record; FIB-4 = Fibrosis-4 score

Discussion

The present national survey assessed barriers and facilitators to MASLD-related liver fibrosis screening among Canadian PCPs following the transition to new nomenclature and diagnostic criteria (1). Our results suggest that many PCPs experience clinical- and system-level barriers that may hinder timely and effective referrals.

Despite recent nomenclature and diagnostic criteria transitions, our findings suggest improved knowledge of MASLD risk factors among PCPs compared to previous surveys in the United States and Canada (27,29,30). In a recent survey of four major cities in the United States, only 54.7% of primary care providers (physicians, physician assistants, and nurse practitioners) were aware of MASLD (30). Additionally, a 2021 national survey of Canadian physicians revealed that only 58% of PCPs were somewhat familiar or not familiar with/unaware of MASLD, but fewer than half identified T2DM and hypertension as high-risk conditions associated with MASLD-associated liver fibrosis (27). T2DM and obesity have been identified as being strongly related to MASLD-related advanced fibrosis progression (12,31–33). Nonetheless, our survey highlights limited clinical awareness of MetALD and its definition. Misclassification is problematic as MetALD represents a distinct disease entity and treatment protocols—MetALD has been associated with higher risks of all-cause mortality (34,35). These knowledge gaps suggest a persistent need for continuing medical education tools to broaden awareness of steatotic liver disease among PCPs.

Interestingly, while a majority of participants correctly identified high-risk conditions, our study revealed inadequate screening for MASLD-related fibrosis in primary care. Approximately half of surveyed PCPs reported screening their patients for MASLD-related fibrosis, a majority of whom relied primarily on ALT and ultrasound as first-line screening tools, which are tests with insufficient sensitivity to detect fibrosis (36–38). While current international guidelines recommend FIB-4 for first-line risk stratification among high-risk populations (8,12,16), our results indicated that only half of those who screened for liver fibrosis used FIB-4. Comparable gaps have been documented elsewhere: in a cross-sectional study of primary care providers in the United States, only 15% used FIB-4 in practice (25). Interestingly, the use of FIB-4 remains suboptimal among specialists. An international survey of hepatologists, gastroenterologists, and other physicians (PCPs, endocrinologists, and medical weight loss specialists) also reported that only 57% of respondents used FIB-4 as the initial non-invasive test for ruling out significant fibrosis (39).

The observed clinical knowledge and implementation gaps have roots in broader, system-level constraints. Almost all respondents reported at least one barrier to MASLD-related fibrosis screening in their practice, particularly system-level barriers including limited time, resources, and screening tools available. These constraints on chronic disease screening programs in Canadian primary care, where competing clinical priorities and limited resources continue to hinder program or guideline implementation (40–42). While FIB-4 is the most recommended non-invasive screening tool due to its ease and diagnostic accuracy, AST, a component of the calculation, is a blood test not currently universally available to PCPs. In 2013, the Ontario Health Technology Advisory Committee recommended that aspartate aminotransferase (AST) testing be restricted to ordering by or on the advice of physicians with experience treating liver disorders. When ordered outside of eligibility, patients may have to pay out of pocket for the test, as set by the private laboratories that they visit for specimen collection (43). In Quebec, hospital and clinical laboratory reflex testing protocols for liver enzymes may automatically cancel AST orders when accompanying ALT is within normal limits, effectively preventing PCPs from calculating FIB-4. Furthermore, transient elastography (FibroScan) is not widely available or reimbursed by provincial health plans across Canada (44), and most are in major cities within specialized liver clinics (45).

The lack of a national guideline for liver fibrosis screening in Canada may also contribute to inconsistent practices in primary care. In our sample, only a small proportion of PCPs were aware of any MASLD/MASH clinical care pathways and actively followed one. Internationally, limited country-specific guidelines have likewise generated confusion regarding liver fibrosis screening and monitoring (46–48). Focus groups conducted in Australia have revealed that risk stratification uncertainty stemmed from a lack of accessible MASLD guidelines for PCPs (47). A cross-sectional survey among physicians across five European countries indicated that 35% of respondents could not identify any MASH-specific clinical guidelines, with some urging specific pathways for addressing common comorbidities (48). Our interprovincial analyses further underscore the role of health systems in shaping primary care practices. Respondents from Alberta—where a provincial MASLD primary care pathway was released in 2023 and a single FIB-4 test panel became orderable in early 2024, eliminating the need for manual calculations by PCPs (49)—reported fewer barriers to accessing FIB-4 and other advanced biomarker panels compared with other regions. Lessons can be learned from Alberta's strategy and applied elsewhere across Canada.

Encouragingly, the respondents reported high enthusiasm for several facilitators for liver fibrosis screening in primary care practices. Among PCPs who did not already have support in their practice, a majority were willing to adopt an integrated EMR clinical care pathway and an automated FIB-4 calculator to flag high-risk cases. Once available, these strategies are unlikely to pose a significant time or resource strain, which was a common concern among PCPs surveyed. Evidence from other settings suggests that automated FIB-4 calculation and EMR-integrated clinical care pathways may help reduce unnecessary referrals and improve the detection of advanced fibrosis (50–53). One important innovation is automated reflex testing for liver disease based on elevated liver enzymes. In a Scottish study of 26,000 participants, this was shown to reduce PCP workload burden, increase cost-efficiency, and detect more people with liver disease (54). Canadian PCPs’ receptiveness to these facilitators suggests that widespread implementation could be a promising avenue to improve fibrosis screening in primary care.

This study has several strengths. To our knowledge, this is the first Canadian study to specifically assess the barriers and facilitators to MASLD-related liver fibrosis screening among primary care physicians. The survey was developed by a multidisciplinary team, ensuring relevance and reflective of real-world primary care practices. Nonetheless, the present study should be interpreted within the context of several limitations. Firstly, our study had a low response rate and may be influenced by non-response bias. Second, our sample skews older and more experienced than the national PCP workforce. While the average age of Canadian PCPs is 49 years (55), non-responders and early career physicians may hold diverging views or practices regarding liver fibrosis screening. Additionally, our study primarily included PCPs from Ontario, Alberta, and Quebec, limiting our findings’ generalizability to other provinces and territories with different guidelines and health care access. Other non-physician primary care providers, such as nurse practitioners, who autonomously practise and manage their own chronic disease rosters in many provinces and territories, were not captured in the present study. As such, a larger national study that also surveys non-physician primary care providers is warranted to capture provincial/territorial and provider-type nuances. Qualitative studies among providers and patients could further contextualize barriers and facilitators to fibrosis screening, particularly regarding test accessibility.

Conclusion

MASLD is a silent condition with a high and growing prevalence. Canadian PCPs play a pivotal role in identifying patients who are at high risk of MASLD-related liver fibrosis. However, the present national survey highlights suboptimal knowledge and implementation of screening tools directed by international guidelines such as FIB-4. These findings support the need for a national MASLD primary care pathway that is readily accessible to PCPs, reducing confusion regarding whom to screen, what specific tools to use for risk stratification, when to refer to specialists, and how to monitor patients.

Funding Statement

This study was supported by the Fatty Liver Alliance through an unrestricted grant from Novo Nordisk.

Contributions:

Conceptualization, DA Dinh, M Betel, M Swain, JV Lazarus, S Joshi, K Cusi, J Kim, M Jung, C Dale, J Burnside, G Sebastiani, S Saeed; Methodology, DA Dinh, G Sebastiani, S Saeed; Formal Analysis, DA Dinh, S Saeed; Investigation, DA Dinh, S Saeed; Resources, M Betel; Data Curation, DA Dinh, S Saeed; Writing – Original Draft, DA Dinh, G Sebastiani, S Saeed; Writing – Review & Editing, DA Dinh, M Betel, M Swain, JV Lazarus, S Joshi, K Cusi, J Kim, M Jung, C Dale, J Burnside, G Sebastiani, S Saeed; Visualization, DA Dinh, S Saeed; Supervision, S Saeed; Project Administration, S Saeed; Funding Acquisition, M Betel.

Ethics Approval:

This study was approved by the Queen's University Research Ethics Board, Canada (#6041010, 2024).

Informed Consent:

N/A

Registry and the Registration No. of the Study/Trial:

N/A

Data Accessibility:

The data to support these findings will be shared upon reasonable request to the corresponding author.

Funding:

This study was supported by the Fatty Liver Alliance through an unrestricted grant from Novo Nordisk.

Disclosures:

M Betel acknowledges grants to the Fatty Liver Alliance from Madrigal Pharmaceuticals, Echosens, Mindray, Perspectum, Google, Sonic Incytes, Inventiva, Regeneron, the Global Liver Institute, Siemens Healthineers, Aegle Medical, Pfizer, the Canadian Liver Foundation, Medscape Education, Sentrex Health Solutions, Novo Nordisk, Intercept Pharmaceuticals, and the Canadian Institute of Health Research; has received consulting fees from Boehringer, Hoffmann-La Roche, Worldwide Clinical Studies, Madrigal Pharmaceuticals, the Global Liver Institute, and Novo Nordisk; has received payment or honoraria from the Translational Medicine Academy, Boehringer, Medscape Education, WebMD, PPD, Sonic Incytes, Inventiva, and MCI (grant to the Fatty Liver Alliance); and has received support for attending meetings and/or travel from the Translational Medicine Academy Boehringer, Regeneron, Madrigal Pharmaceuticals, Arizona Liver Health, and the Liver Forum, outside of the submitted work. M Swain has served in an advisory role for Gilead, Ipsen, Novo Nordisk, Advanz, Abbott, GSK, Mirum, and Boehringer Ingelheim; has served as a speaker for Ipsen and Gilead; and has received clinical trial or research support from Gilead, BMS, GSK, Cymabay, Intercept, Kowa, Novo Nordisk, Pfizer, Ancella, Merck, Galectin, Calliditas, Ipsen, Madrigal, Roche, Altimmune, 89Bio, Inventiva, and Boehringer Ingelheim. JV Lazarus acknowledges grants to ISGlobal from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Madrigal, MSD, Novo Nordisk, Pfizer, and Roche Diagnostics; has received consulting fees from Echosens, the Global NASH Council, NovoVax, GSK, Novo Nordisk, Prosciento, and Pfizer; and has received payment or honoraria for lectures from AbbVie, Echosens, Gilead Sciences, Janssen, Moderna, MSD, Novo Nordisk, and Pfizer, outside of the submitted work. S Joshi has received speaking and advisory board consulting fees from Abbvie Sciences, Gilead Sciences, Novo Nordisk, and Ipsen Pharmaceuticals. K Cusi has received research support (to institution) from Boehringer Ingelheim, Echosens, Inventiva, Labcorp, and Perspectum; has served as a consultant for Aligos Therapeutics, Arrowhead, AstraZeneca, 89bio, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Novo Nordisk, ProSciento, Sagimet Biosciences, Siemens USA, Zealand Pharma, and Terns Pharmaceuticals. JW Kim has acted as speaker for and served an advisory board member for Abbott, AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, embecta, Eisai, Eli Lilly, Novo Nordisk, Otsuka, Searchlight, Takeda, Teva and Sanofi; received consultancy honoraria from Abbott, ALK, AstraZeneca, Bayer, Boerhinger-Ingelheim, Eli Lilly, GSK, Idorsia, Linpharma, MiravoPharm, Novo Nordisk, Pfizer, Sanofi, Searchlight, Takeda, Teva, and Valeo; is part of the study team for Idorsia and Novo Nordisk clinical trial; and has received research fundings from Bayer and Eisai. H-M Jung has received clinical consulting fees from Roche; and has received speaker fees from Gillead, Abbvie, and the Primary Care MASLD/MASH Meetings. C Dale has acted as a speaker, consultant, or advisory board member for Gilead and AbbVie. G Sebastiani has acted as speaker for Merck, Gilead, Abbvie, Novo Nordisk, and Pfizer; served as an advisory board member for Pfizer, Merck, Novo Nordisk, and Gilead; and has received unrestricted research funding from Theratechnologies Inc. S Saeed has served as an advisory board member for Novo Nordisk. DA Dinh and J Burnside have nothing to disclose.

Peer Review:

This article has been peer reviewed.

Animal Studies:

N/A