Prevalence and severity of MASLD and fibrosis using transient elastography: A cross-sectional screening in Lower Mainland, British Columbia, Canada

Abstract

Background:

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a leading cause of liver disease worldwide. We aimed to assess the prevalence and severity of MASLD and fibrosis among asymptomatic individuals with no known history of liver disease in British Columbia (BC), Canada.

Methods:

We conducted a cross-sectional, population-based screening study of 2,782 individuals in the Lower Mainland of BC. Baseline demographics were collected, and transient elastography was performed. The prevalence and severity of MASLD and liver fibrosis were calculated.

Results:

MASLD affected 53.1% of participants, with 34.0% having severe hepatic steatosis, 6.5% moderate hepatic steatosis, and 12.6% mild hepatic steatosis. Factors associated with a higher MASLD incidence included non-lean BMI (OR 5.50, p <0.001), hypertension (OR 1.29, p = 0.014), diabetes (OR 1.33, p = 0.026), and South Asian ethnicity (OR 1.36, p = 0.014), while female gender was protective (OR 0.81, p = 0.015). Non-lean BMI (OR 5.71, p <0.001), hypertension (OR 1.33, p = 0.002), and diabetes (OR 1.34, p = 0.010) were associated with more severe steatosis. Fibrosis was present in 7.2% of participants, with 4.4% having moderate fibrosis, 1.9% having severe fibrosis, and 0.9% having cirrhosis. Diabetes (OR 1.93, p <0.001) and non-lean BMI (OR 2.37, p <0.001) were associated with a higher prevalence of fibrosis, while East Asian ethnicity was protective (OR 0.50, p <0.001). Non-lean BMI (OR 2.35, p <0.001) and diabetes (OR 1.96, p <0.001) were linked to higher fibrosis severity, while East Asian ethnicity remained protective against severe fibrosis (OR 0.50, p <0.001).

Conclusions:

There is a significant burden of liver steatosis and fibrosis in BC, Canada, which highlights the need for comprehensive MASLD screening guidelines.

Lay Summary

Determining the prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD) and identifying the associated risk factors is critical for public health planning and resource allocation. To date, no studies have assessed the burden or characteristics of MASLD in Canada. This study examines the prevalence and severity of MASLD and liver fibrosis in asymptomatic individuals in British Columbia, Canada, with no known history of liver disease, and identifies factors associated with liver steatosis and fibrosis.

A total of 2,782 participants were screened using transient elastography to measure liver fat and stiffness. Over half (53.1%) of the participants were found to have MASLD, with 34% having severe disease, 6.5% moderate, and 12.6% mild. People who were overweight or obese, had high blood pressure, diabetes, or were of South Asian ethnicity were more likely to have MASLD. Women were found to be less likely to develop the condition.

Additionally, 7.2% of participants had liver fibrosis, a condition in which scar tissue forms in the liver. This included 4.4% with moderate fibrosis, 1.9% with severe fibrosis, and 0.9% with cirrhosis (advanced scarring). Those with diabetes or who were overweight or obese were at a higher risk for fibrosis, while participants of East Asian descent had a lower risk of developing severe fibrosis.

This study highlights that MASLD and liver fibrosis are common in the population, especially among individuals with metabolic risk factors. The findings emphasize the need for improved screening to detect these liver conditions early and prevent further liver damage.

Introduction

Metabolic dysfunction–associated steatotic liver disease (MASLD) is one of the leading causes of chronic liver disease globally. The prevalence of MASLD is estimated to be over 32% worldwide, and projections indicate an alarming increase, reaching a prevalence of 55.7% by 2040 (1,2). This escalating disease burden is driven by the epidemic of metabolic diseases, especially diabetes and obesity. MASLD encompasses a spectrum of diseases, including simple steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. While the majority of individuals with MASLD are asymptomatic, up to 25% of individuals with MASLD develop metabolic dysfunction-associated steatohepatitis (MASH), and an additional 20% of people with MASH progress to significant fibrosis and cirrhosis (3,4). MASH is the second-leading indication for liver transplantation in North America. However, with recent therapeutic advances in both chronic hepatitis B and hepatitis C viruses, MASH is projected to become the leading indication for transplantation over the next 10 years (5). Hence, early recognition and management of liver steatosis in the general population are imperative for preventing disease progression.

Transient elastography (TE) is a validated non-invasive technique for measuring the shear wave speed of liver parenchyma and correlating it with the degree of liver fibrosis. The incorporation of the continuous attenuation parameter score with elastography allows for the measurement of ultrasound attenuation to determine the extent of hepatic steatosis. Most population screening studies of MASLD utilize ultrasonography, which likely underestimates the true prevalence of MASLD. TE demonstrates significantly greater sensitivity in detecting liver steatosis, with the ability to identify hepatic steatosis from as low as 10% fatty infiltration. In contrast, ultrasonography exhibits poor sensitivity, detecting steatosis with only 55% accuracy when hepatic fat content is less than 20% (6,7).

While liver biopsy remains the gold standard for assessing the severity of hepatic fibrosis, it is an invasive procedure prone to inter- and intra-reader variability and high sampling error due to the low sampling volumes. From a patient's perspective, there is a risk of significant discomfort, bleeding, and, rarely, biopsy-associated mortality. Magnetic resonance elastography is a newer diagnostic tool with excellent diagnostic accuracy in detecting liver fibrosis. However, its application is limited by the high cost and limited availability. TE, while limited by non-fasting states, the presence of liver inflammation, and elevated BMI, may overestimate the degree of fibrosis, but it offers the advantages of being accessible, portable, and easy to learn how to operate. Also, it provides immediate results, making it an ideal instrument for population screening.

Determining the prevalence of MASLD and identifying associated risk factors is critical for public health planning and resource allocation. To date, no previous studies have assessed the disease burden or characteristics of MASLD in Canada. To address this need, this study aimed to estimate the prevalence and severity of MASLD and fibrosis among the asymptomatic British Columbia (BC) population with no known history of liver disease and to identify characteristics associated with liver steatosis and fibrosis.

Methods

Study population

We conducted a cross-sectional, population-based screening study in the Lower Mainland, BC, Canada. Participants voluntarily enrolled between April 20, 2022, and August 27, 2023, through educational seminars, medical channels, and social media platforms facilitated by the Canadian Liver Foundation.

Interested participants underwent interviews with a study coordinator to determine eligibility. Volunteers were excluded from the study if they were <18 years of age (n = 1), had missing values (n = 4), or had a history of viral hepatitis (n = 63), chronic liver disease (hemochromatosis [n=1]), autoimmune hepatitis (n = 2), primary biliary cholangitis (PBC) (n = 1), or engaged in significant alcohol consumption (n = 97), defined as >30 g/day of alcohol for men and >20 g/day for women. Participants with missing TE (ie, FibroScan) (n = 292) or unreliable FibroScan results (n = 66), as defined below, were excluded.

Data collection

The study coordinators interviewed the participants to collect baseline demographics, including age, sex, ethnic background, and the name of their family physician if they had one. They also asked about comorbid conditions, including diabetes, hypertension, hyperlipidemia, and cardiac disease. A focused liver history was obtained, including underlying relevant symptomatology, underlying chronic liver disease, and patterns of alcohol intake. Each participant was assigned a unique study number, anonymized, and their data were encrypted and password-protected.

Assessment of liver steatosis and fibrosis

Due to the COVID-19 pandemic, mobile screening units were not feasible. Hence, TE assessments were performed in two designated community pharmacy locations with adequate safety protocols in place, as per the BC provincial guidelines. TE was performed by trained FibroScan technicians using the FibroScan Compact 530 (Echosens, Paris, France) according to standard protocol.

As previously reported, FibroScan evaluation was deemed unreliable if fewer than 10 valid examinations were obtained or when the interquartile range/median ratio was >0.30 (8). Controlled attenuation parameter (CAP) score >248 dB/m was considered as MASLD with values <248, 248–267, 268–279, and >280 dB/m considered as S0 (none), S1 (mild), S2 (moderate), and S3 (severe) steatosis, respectively (9). The presence of fibrosis was defined by TE measurement as >7.5 kPa. The fibrosis stage was characterized by <7.4, 7.5–10, 10–14, and >14 kPa for F0-1, F2, F3, and F4, respectively (10).

Statistical analysis

Categorical variables were presented as frequencies (%), while continuous variables were expressed as mean (SD) or median with interquartile range, as appropriate. BMI was categorized as lean for BMI <23 kg/m² for Asian participants and <25 kg/m² for non-Asian participants. Univariate analysis assessed associations between clinical characteristics with MASLD and fibrosis prevalence using independent sample t-tests or ANOVA. Ordinal regression was used to assess the severity of steatosis and fibrosis. Odds ratios (OR) with 95% CIs were calculated using multinomial logistic regression for prevalence, while multiordinal logistic regression was employed for the severity of MASLD and fibrosis. Significant characteristics from univariate analysis and clinically relevant covariates (age, sex, diabetes, hypertension, dyslipidemia, BMI) were included in regression models. A two-sided p value <0.05 was considered statistically significant. Analyses were performed using IBM SPSS version 29 (Armonk, New York), and figures were generated using GraphPad Prism version 9 (Boston, Massachusetts).

Results

Baseline characteristics

A total of 2,782 participants were enrolled in the study. Baseline characteristics are outlined in Table 1. The median age was 60 years (range, 19–91 years), with a female predominance (n = 1,582, 57%). The majority of participants self-identified as East Asian (n = 1,316, 47%), followed by white (n = 832, 30%), South Asian (n = 524, 19%), other (n = 73, 3%), native Hawaiian/Pacific islander (n = 24, 1%), Black/African heritage (n = 10, <1%), and Indigenous (n = 3, <1%). The mean BMI in the cohort was 26.0 (SD 5.2) kg/m². Comorbidities included diabetes in 369 (13%) participants, hypertension in 754 (27%) participants, hyperlipidemia in 820 (29%) participants, and cardiovascular disease in 218 (8%) participants.

Table 1:

Baseline clinical characteristics

Characteristic	No. (%)*; n = 2,782
Age, y, median (range)	60 (19–91)
Gender, male	1,200 (43)
Race
White	832 (30)
Asian	1,316 (47)
South Asian	524 (19)
Native Hawaiian / Pacific Islander	24 (1)
Black / African heritage	10 (<1)
Indigenous	3 (<1)
Other	73 (3)
BMI, kg/m2, mean (SD)	26.0 (5.2)
Diabetes	369 (13)
Hypertension	754 (27)
Hyperlipidemia	820 (29)
Cardiovascular disease	218 (8)

^*Unless otherwise specified

Prevalence and severity of liver steatosis

MASLD was present in 1,478 (53%) participants (Figure 1). In a comparative analysis, the prevalence of MASLD was not significantly associated with hyperlipidemia, cardiovascular disease, or having a family physician. However, participants from the South Asian community (63% versus 51%, OR 1.36, p = 0.014) or those with metabolic comorbidities including non-lean BMI (67% versus 27%, OR 5.50, p <0.001), hypertension (63% versus 50%, OR 1.29, p = 0.014), and diabetes (63% versus 52%, OR 1.33, p = 0.026) independently had a significantly higher prevalence of MASLD on multinomial analysis. In contrast, being a female was protective (51% versus 56%, OR 0.81, p = 0.015) (Figure 2 and Table 2).

Figure 1: The prevalence and severity of liver steatosis and fibrosis. A) prevalence of MASLD, B) prevalence of different severities of liver steatosis, and C) prevalence of different severities of liver fibrosis.

MASLD = Metabolic dysfunction-associated steatotic liver disease

*p < 0.001

Figure 2: Characteristics associated with the prevalence of liver steatosis. A) gender, B) South Asian ethnicity, C) BMI, D) presence of diabetes, and E) presence of hypertension.

*p < 0.05

†p < 0.001

Table 2:

Multinomial regression of independent predictors of steatosis and fibrosis prevalence

	Steatosis prevalence		Fibrosis prevalence
Characteristic	Odds ratio (95% CI)	p value	Odds ratio (95% CI)	p value
Age	1 (0.99–1.01)	0.89	1 (0.99–1.01)	0.85
Gender
Male	1	0.015	1	0.78
Female	0.81 (0.68–0.96)		0.96 (0.71–1.29)
Race
White	1		1
South Asian	1.36 (1.06–1.73)	0.014	0.86 (0.58–1.27)	0.44
East Asian	1.14 (0.94–1.38)	0.18	0.50 (0.35–0.71)	<0.001
Black/African	0.37 (0.09–1.63)	0.19	2.41 (0.48–12.08)	0.29
Indigenous	–	–	–	–
Native Hawaiian/Pacific Islander	1.38 (0.56–3.42)	0.48	1.63 (0.53–5.06)	0.40
Other	1.26 (0.74–2.14)	0.40	0.51 (0.18–1.46)	0.21
BMI
Lean	1	<0.001	1	<0.001
Non-lean	5.50 (4.57–6.61)		2.37 (1.59–3.52)
Hypertension
No	1	0.014	1	0.12
Yes	1.29 (1.05–1.57)		1.31 (0.93–1.84)
Diabetes
No	1	0.026	1	<0.001
Yes	1.33 (1.04–1.73)		1.93 (1.33–2.82)
Hyperlipidemia
No	1	0.30	1	0.54
Yes	1.10 (0.92–1.33)		1.11 (0.79–1.55)

Among those with MASLD, most had advanced steatosis, with 64% having severe steatosis, 12% moderate steatosis, and 24% mild steatosis (Figure 1). On multiordinal analysis, after adjusting for age, gender, race, and metabolic risk factors, non-lean BMI (OR 5.71, p <0.001), hypertension (OR 1.33, p = 0.002), and diabetes (OR 1.34, p = 0.010) remained significant risk factors associated with more severe liver steatosis (Table 3).

Table 3:

Multiordinal regression of independent predictors of steatosis and fibrosis severity

	Steatosis severity		Fibrosis severity
Characteristic	Odds ratio (95% CI)	p value	Odds ratio (95% CI)	p value
Age	1 (0.99–1.00)	0.59	1 (0.99–1.01)	0.8
Gender
Male	1	0.064	1	0.72
Female	1.15 (0.99–1.34)		0.95 (0.70–1.27)
Race
White	1		1
South Asian	1.24 (1.00–1.55)	0.050	0.86 (0.59–1.27)	0.460
East Asian	1.12 (0.94–1.33)	0.21	0.50 (0.35–0.70)	<0.001
Black/African	0.43 (0.11–1.69)	0.23	2.39 (0.48–11.80)	0.28
Indigenous	–	–	–	–
Native Hawaiian/Pacific Islander	1.56 (0.70–3.51)	0.28	–
Other	1.25 (0.78–2.00)	0.36	0.50 (0.17–1.44)	0.20
BMI
Lean	1	<0.001	1	<0.001
Non-lean	5.71 (4.78–6.82)		2.35 (1.58–3.50)
Hypertension
No	1	0.002	1	0.12
Yes	1.33 (1.11–1.59)		1.31 (0.93–1.84)
Diabetes
No	1	0.010	1	<0.001
Yes	1.34 (1.07–1.68)		1.96 (1.35–2.86)
Hyperlipidemia
No	1	0.60	1	0.49
Yes	1.05 (0.88–1.24)		0.89 (0.64–1.24)

Prevalence and severity of fibrosis

Fibrosis was present in 7.2% of participants; 4.4% had moderate fibrosis (F2), 1.9% had severe fibrosis (F3), and 0.9% had cirrhosis (F4). Diabetes (12.5% versus 6.4%, OR 1.93, p <0.001) and non-lean BMI (9.1% versus 3.5%, OR 2.37, p <0.001) significantly increased fibrosis prevalence. In contrast, members of the East Asian community had lower rates (4.8% versus 9.4%, OR 0.50, p <0.001) (Figure 3 and Table 2). Non-lean BMI and diabetes were also linked to higher fibrosis severity, with OR 2.35 (p <0.001) and 1.96 (p <0.001), respectively. East Asian ethnicity remained protective against fibrosis severity (OR 0.50, p <0.001) (Table 3).

Figure 3: Characteristics associated with the prevalence of liver fibrosis: A) East Asian ethnicity, B) BMI, and C) diabetes *p < 0.001.

Association between liver steatosis and fibrosis

The severity of liver steatosis was significantly associated with the prevalence of fibrosis. Among participants with S0, S1, S2, and S3 steatosis, 3.5%, 6.3%, 7.2%, and 12.8%, respectively, had fibrosis (p <0.001) (Figure 4). Similarly, participants with more advanced steatosis were more likely to have more advanced fibrosis. On multivariate analysis, after adjusting for classic metabolic risk factors, a higher steatosis score remained a significant and independent risk factor for the increased prevalence and severity of liver fibrosis (Table 4).

Figure 4: Association between liver steatosis and fibrosis: A) prevalence of liver fibrosis stratified by liver steatosis severity, and B) liver fibrosis severity stratified by liver steatosis severity.

Table 4:

Multiordinal regression of liver steatosis severity on fibrosis severity

	Fibrosis severity
Characteristic	Odds ratio (95% CI)	p value
Age	1 (0.99–1.01)	0.96
Gender
Male	1	0.59
Female	0.92 (0.68–1.24)
Race
White	1
South Asian	0.85 (0.57–1.25)	0.40
East Asian	0.49 (0.34–0.70)	<0.001
Black/African	3.12 (0.61–15.87)	0.17
Indigenous	–	–
Native Hawaiin/Pacific Islander	1.27 (0.39–4.12)	0.69
Other	0.47 (0.16–1.36)	0.16
BMI
Lean	1	0.094
Non-lean	1.44 (0.94–2.22)
Hypertension
No	1	0.24
Yes	1.23 (0.87–1.72)
Diabetes
No	1	0.002
Yes	1.81 (1.24–2.64)
Hyperlipidemia		0.43
No	1
Yes	0.87 (0.62–1.22)
Steatosis Score
S0	1
S1	1.63 (0.95–2.79)	0.076
S2	1.96 (1.02–3.77)	0.043
S3	3.31 (2.24–4.87)	<0.001

Discussion

To the best of the authors' knowledge, this study represents the first population-based screening to assess the prevalence and severity of MASLD and fibrosis in Canada and was one of the largest cross-sectional screening studies using TE. We identified an alarming proportion of people with liver disease, with 53% of asymptomatic individuals with an unknown history of liver disease found to have MASLD and 7.2% exhibiting fibrosis through TE.

The prevalence of MASLD in our study far exceeds the previously estimated 25% prevalence in Canada and the global prevalence of up to 32% (2,11). Several factors may contribute to this disparity. First, TE exhibits much greater sensitivity in detecting liver steatosis and is capable of identifying hepatic steatosis from as low as 10% fatty infiltration (7). In contrast, abdominal ultrasonography, the predominant modality used in population screening studies, demonstrates a poor sensitivity of only 55% for detecting steatosis when hepatic fat content is less than 20% (6). Consequently, the prevalence of MASLD is likely underreported when using abdominal ultrasonography. Screening studies utilizing elastography-based measurements, such as those by Kwak et al and Lee et al in South Korea (reporting 52% and 42.9%, respectively), and Zhang et al and Kim et al in the United States (reporting 56.7% and 47.8%, respectively), consistently report a higher MASLD prevalence (12–15). The elevated prevalence of MASLD in our study may indicate a genuine rise in disease occurrence, particularly considering the increasing prevalence of metabolic diseases in the population. Although there is a lack of data on the trends of metabolic syndrome in Canada, information from the United States reveals a surge in the prevalence of metabolic syndrome from 32.5% to 36.9% between 2011 and 2016 (16). Lastly, as participants in our study were self-volunteered, individuals with greater risk factors or concerns about their liver health may have been more inclined to participate. This could potentially result in self-selection bias, although the well-recognized epidemiologic phenomenon of “healthy user bias” would have been expected to mitigate our findings (17).

Among the participants with MASLD, the majority (64%) exhibited severe S3 steatosis. MASLD is often a silent disease, with no symptoms until advanced fibrosis or cirrhosis develops, making it challenging to detect without screening, unless it is discovered incidentally. Current guidelines do not recommend routine general population-based screening for MASLD. The most recent American Association for the Study of Liver Disease (AASLD) MASLD 2023 guidelines recommend that high-risk individuals, including those with diabetes, obesity, a family history of cirrhosis, or more than mild alcohol consumption, should be screened for advanced fibrosis using the FIB-4 score (18). However, indications for screening for MASLD are lacking. Furthermore, a Canadian survey of primary care physicians showed that 58% of respondents were only somewhat familiar or unfamiliar with MASLD (19). The inadequate understanding and awareness of MASLD among health care providers, coupled with the absence of clear screening recommendations, contribute to the oversight of MASLD, leading to untimely management and more severe steatosis. As demonstrated in our study, the increased severity of steatosis is an independent risk factor for the increased risk and severity of fibrosis; hence, more guidance on MASLD screening is required.

A non-lean BMI emerged as the strongest predictor in our study for both the prevalence and severity of liver fibrosis and steatosis. The contributory role of obesity in MASLD is well-studied and established. A meta-analysis of 21 cohort studies, involving a total of 381,655 participants, reported that obesity independently led to a 3.5-fold increased risk of developing MASLD (20), which is comparable to the OR of 5.5 found in our study. As a result, weight loss stands as one of the pillars of MASLD management, with studies demonstrating that a weight loss of 3%–5% can improve steatosis, while a more substantial reduction exceeding 10% may improve MASH and fibrosis (18).

Despite the established association between obesity and MASLD, the entity of lean MASLD has been increasingly recognized. The prevalence of lean MASLD is reported to range from 10%–20% among individuals with MASLD (21). It is not surprising that our study falls at the higher end of this spectrum, with 20% (251/1227) of participants with MASLD being lean, given the substantial proportion of Asians in our study. According to Statistics Canada, Asians accounted for over 45% of the Metro Vancouver population in 2021, and this figure is likely to have increased by the time of our study (22). Ethnic differences in MASLD prevalence are likely driven by genetic predisposition, such as the PNPLA3 polymorphism, which appears to play a crucial role in the development of MASLD in the lean population. The at-risk PNPLA3 I148M polymorphism is found in 13%–19% of the general population in Asian studies, compared with 4% in Caucasians, 2% in African Americans, and 25% in Hispanics (23,24). Another identified genetic risk factor is a point mutation in another gene, TM6SF2, which has also been found to be more frequent in East Asians (34%) compared to Europeans (26%), Hispanics/Latinos (10%), and Africans (6%) (25).

Our study has several limitations. First, there are no standardized cut-off values for CAP and elastography to assess liver steatosis and fibrosis scores, respectively. We utilized CAP cut-offs reported by Karlas et al, which were determined through a meta-analysis of 19 studies containing histology-verified CAP data for steatosis grading (9). Elastography values for fibrosis scores were adopted from the findings of Bonder et al (10). The use of different cut-off values in our study may limit comparisons with other studies. Second, as this was a screening study, we were unable to conduct liver biopsies to verify the elastography results histologically. TE, despite being a portable, convenient, and cost-effective screening modality, has limitations in accuracy, as indicated by the summary area under the receiver operator curve values of 0.83 for the diagnosis of significant fibrosis, 0.85 for advanced fibrosis, and 0.89 for cirrhosis (26). Without histology, we were also unable to determine the presence of MASH. Third, we did not have access to patients' medical records, and medical comorbidities were self-reported by the participants, which could potentially lead to inaccurate information that could affect the analysis. Finally, additional investigations, such as routine biochemistries, were not conducted, potentially overlooking not-yet-diagnosed risk factors, such as metabolic disorders, acute hepatitis, liver inflammation, or extra-hepatic cholestasis, which could lead to an overestimation of liver stiffness.

Conclusion

Our study highlights a significant burden of liver steatosis and fibrosis among asymptomatic individuals with an unknown history of liver disease in BC, Canada. High-risk populations for steatosis and fibrosis include males with non-lean BMI, hypertension, and diabetes. Early recognition and management of liver steatosis are imperative to prevent progression to fibrosis. There is a strong need for more comprehensive guidelines on MASLD risk-stratification and screening.

Funding Statement

This research was supported by the Canadian Liver Foundation. The steering committee was involved in the study design of the project.

Contributions:

Conceptualization, D Chahal, E Yoshida, P Kwan; Data curation, D Chahal, J Kim, E Yoshida, P Kwan; Investigation, K Zhu, H Bedi; Methodology, D Chahal, E Yoshida, P Kwan; Writing – Original Draft, K Zhu, H Bedi; Writing – Review & Editing, D Chahal, J Kim, E Yoshida, P Kwan.

Ethics Approval:

This study was conducted in accordance with the Declaration of Helsinki and approved by the University of British Columbia Clinical Research Ethics Board.

Informed Consent:

The participants provided witnessed written consent using a prepared subject information and informed consent form. The authors confirm that informed consent was secured from all study participants whose personal information is included in this article.

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

N/A

Data Accessibility:

The data underlying this article will be shared on reasonable request to the corresponding author.

Funding:

This research was supported by the Canadian Liver Foundation. The steering committee was involved in the study design of the project.

Disclosures:

The authors declare no competing interests.

Peer Review:

This article has been peer reviewed.

Animal Studies:

N/A