Abstract
Background
Endoscopic retrograde cholangiopancreatography (ERCP) is valuable in management of primary sclerosing cholangitis (PSC). Herein, we characterize individuals with PSC who underwent ERCP on-demand at a high-volume quaternary centre, with evaluation of pathology results and short-term postprocedural outcomes.
Methods
This retrospective cohort study evaluated patients with PSC who underwent ERCP at St Michael’s Hospital between April 2011 and July 2021. Chart review was conducted to collect clinical, procedural, and pathology data, and reported post-ERCP complications within 90 days. Logistic regression analyses were conducted to evaluate factors associated with post-ERCP complications and placement of a biliary stent.
Results
One hundred and sixty-seven patients with PSC underwent 464 ERCPs (69% males, median age 45 years). The median duration of PSC diagnosis prior to ERCP was 6.7 years and 42% of procedures were in patients with cirrhosis. Symptoms pre-ERCP included jaundice, abdominal pain, subjective fevers, and pruritus. Stent insertion at procedure was associated with presentations with jaundice or elevated bilirubin, prior stent insertion, and/or concern for malignancy. Stent insertion was also associated with post-ERCP complications within 90 days. Neoplastic pathology was identified in 20% of cytology samples and 27% of biliary biopsies. There were no significant differences in symptomology at presentation between patients with and without neoplastic pathology.
Conclusion
Primary sclerosing cholangitis patients undergoing ERCP have high symptom burden and rates of neoplastic pathology, with high rates of recurrent obstruction post-ERCP. Stent insertion is associated with a sicker PSC phenotype and higher risk of post-ERCP complications. Future studies are needed to further explore the role of ERCP in management of PSC.
Keywords: PSC, ERCP, stent, pancreatitis, cholangiocarcinoma
Introduction
Primary sclerosing cholangitis (PSC) is a rare, immune-mediated liver disease characterized by inflammation and stricturing of the intra- and/or extrahepatic biliary ducts with resultant cholestasis and fibrosis.1 While the disease course is variable, it is chronic and progressive with complications including biliary obstruction, recurrent cholangitis, and cholangiocarcinoma.2 Endoscopic retrograde cholangiopancreatography (ERCP) is a valuable diagnostic and therapeutic tool to relieve obstruction, obtain source control, and obtain tissue samples for pathology review.3,4
Management of PSC can be challenging in clinical practice, especially when considering ERCP in individuals with PSC (PSC-ERCP) given the increased risk of complications, such as pancreatitis or cholangitis, reported.5-7 Results vary across studies, likely due to differences in disease variability, patient profiles, and endoscopist expertise. Furthermore, clinical practice involving the role of PSC-ERCP varies globally, including scheduled evaluation with or without dilation of dominant biliary strictures instead of ERCP on-demand.8,9 The benefit of ERCP in PSC remains debated, with symptom and biochemistry improvements reported in some studied, but the impact on transplant-free survival remains unclear.10
Guidelines recommend PSC-ERCP to be performed in a high-volume centre with advanced operator expertise, given the potential technical challenges and complexity of PSC care. In this study, we aim to characterize the clinical, procedural, and pathology characteristics of individuals with PSC undergoing ERCP on-demand at a high-volume quaternary referral centre designated as a centre of excellence for therapeutic endoscopy, along with evaluation of complications postprocedure and associated risk factors in this population.
Methods
Cohort derivation
This was a retrospective study conducted at St Michael’s Hospital, a high-volume, quaternary care therapeutic endoscopy centre in Toronto, Ontario, Canada. The cohort was derived by evaluating all inpatient and outpatient individuals who underwent ERCP at the centre from April 1, 2011 to July 31, 2021 inclusive using the Canadian Classification of Health Interventions ERCP procedural code, followed by chart review to confirm whether an ERCP was indeed performed, and evaluation of whether the individual had an established diagnosis of PSC in keeping with guideline-established criteria.11-13 Those who were post-liver transplant were excluded (Figure 1). A comprehensive chart review was then conducted for all eligible patients via their electronic medical records and/or physician office charts available at the hospital, when applicable.
Figure 1.
Study flowchart.
Descriptives and definitions
The primary aim of the study was to describe the characteristics of patients with PSC undergoing ERCP. Patient demographics comprised age, sex, race, weight, height, body mass index, smoking status, and alcohol use. Clinical profile descriptives included duration of PSC diagnosis, concurrent inflammatory bowel disease (IBD) diagnosis and IBD type, presence/absence of cirrhosis, liver transplantation listing status, and concurrent medical comorbidities. Pre-ERCP symptoms, procedural indications, and previous endoscopic treatment were abstracted. Radiological disease characteristics were documented, including biliary disease involvement, presence/absence of dominant stricture, and location of target lesion.
Detailed ERCP procedural details were extracted including brushings, stent insertion/removal, balloon dilatation, sphincterotomy, stone/sludge removal, and reported technical success at end of procedure (ie, relief of biliary tree obstruction). Documentation of a dominant stricture (as per ERCP definition of a diameter of ≤1.5 mm of the common bile duct [CBD] or of ≤1 mm of the hepatic duct) or relevant stricture (clinical definition of any biliary stricture of the CBD or hepatic ducts associated with signs/symptoms of obstructive cholestasis and/or bacterial cholangitis) was abstracted from procedural documentation; post hoc review of ERCP imaging for these definitions was not performed.
Bloodwork pre-ERCP and post-ERCP (up to 90 days) were recorded. Where available, pathology details from sampled target lesions were abstracted and categorized into reactive/inflammatory versus suspicious for dysplasia/malignancy.
A secondary aim of the study was to evaluate incidence and risk factors for centre documented post-ERCP complications, which included recurrent biliary blockage, pancreatitis, cholangitis, gastrointestinal bleeding, stent failure, cholecystitis, luminal perforation/leak, cardiovascular/respiratory complications, and death within 90 days of the procedure. Where available, hospital readmissions and ERCP reintervention within 90 days of the procedure were also evaluated.
Statistical analyses
Descriptive categorical variables were presented as percentages, and continuous variables as medians with interquartile range (IQR). Continuous variables were compared with Wilcoxon rank-sum test, with categorical variables compared with Chi-square or Fisher’s exact testing.
Variables associated with stent insertion were assessed with univariate logistic regression. Changes in alkaline phosphatase (ALP) and total bilirubin pre- and post-ERCP were evaluated using generalized estimating equations with correlation structures accounting for time lag, stratified by stent insertion, balloon dilatation, and cirrhosis status. To evaluate risk factors for post-ERCP complications, univariate logistic regression analyses were performed, followed by using a threshold of a P-value of <.25 and clinical judgement to select variables for multivariable regression using a generalized linear mixed model to account for clustering by individual. A P-value of <.05 was considered statistically significant.
This retrospective study was approved by the Unity Health Toronto Research Ethics Board.
Results
Patient characteristics
Of 21,467 coded ERCPs done in 9528 individuals, 464 ERCPs were done in 167 individuals with PSC (Figure 1), with PSC-ERCPs constituting 1.7% of all ERCPs. On average, each PSC patient had 2.8 procedures, compared to 2.3 procedures/person for the overall population. At first ERCP at St Michael’s hospital, the median age was 46 years old (IQR 34-58), 69% were male, 52% had at least 1 prior ERCP at an alternate peripheral hospital, and 23% had a prior biliary stent. Ethnicity was reported in 75 individuals (45%), with the majority identifying as Caucasian (56%), followed by Asian (24%). Concurrent IBD diagnosis was reported in 66% of patients, of whom 74% had ulcerative colitis and 18.5% had Crohn’s disease. Alcohol use history was obtained in 99 individuals, of which 29% did not drink any alcohol, 49% drank <10 g/day for females and <20 g/day for males, while 21% drank >10 g/day for females >20 g/day for males. Due to the significant proportion of missing data (n = 68), alcohol use was not evaluated as a risk factor in subsequent analyses.
When evaluating patient characteristics pre-ERCP, the median duration of PSC diagnosis was 6.7 years (IQR 2.2-11.0) with median age at procedure of 45 years (IQR 31-59) (Table 1); 169 procedures (42%) were performed in patients with cirrhosis, 207 (47%) in patients taking ursodeoxycholic acid (UDCA), and 95% were in patients not listed for transplant at time of ERCP. Due to data missingness, MELD and MELD-Na scores were not available for most patients. Co-morbidities at time of ERCP included cardiovascular disease in 12%, respiratory in 2.6% and renal in 2.6%. Common symptoms reported pre-ERCP were jaundice/scleral icterus (56%), abdominal pain (43%), subjective fevers (30%), and pruritus (25%). The most common indications for ERCP were biliary obstruction (82%), cholangitis (31%), and assessment for malignancy (22%). Bloodwork pre-ERCP demonstrated median ALP 362 U/L (IQR 231-552) and median total bilirubin 76 µmol/L (IQR 29-141).
Table 1.
Patient and clinical characteristics at procedure.
| Study variable | n (%) of ERCPs with details |
|---|---|
| Patient characteristics pre-ERCP | |
| Age at ERCP (median, IQR) | 45 (31-59) |
| Duration of known PSC diagnosis (years, median, IQR) | 6.7 (2.2-11.0) |
| Male sex (n, %) | 328 (71) |
| On ursodeoxycholic acid (n, %) | 207 (47) |
| Cirrhosis (n, %) | 169 (42) |
| Not listed for transplant (n, %) | 432 (95) |
| Endoscopically active IBD at time of ERCP | 57 (19) |
| Symptoms pre-ERCP | |
| Pruritus (n, %) | 106 (25) |
| Chills (n, %) | 59 (14) |
| Rigors (n, %) | 19 (4.4) |
| Subjective fevers (n, %) | 131 (30) |
| Abdominal pain (n, %) | 190 (43) |
| Jaundice (n, %) | 247 (56) |
| Confusion/impaired consciousness (n, %) | 5 (1.2) |
| Bleeding (n, %) | 4 (0.9) |
| Ascites development (n, %) | 16 (3.7) |
| Hypotension (n, %) | 7 (1.6) |
| Weight loss (n, %) | 44 (10) |
| ERCP indication | |
| Cholangitis (n, %) | 141 (31) |
| Biliary obstruction (n, %) | 371 (82) |
| Concern for malignancy (n, %) | 99 (22) |
| Other (n, %) | 64 (14) |
| Bloodwork parameters (median 4 days pre-ERCP, IQR 0-16) | |
| AST (U/L) (median, IQR) | 89 (54-136) |
| ALT (U/L) (median, IQR) | 94 (55-156) |
| ALP (U/L) (median, IQR) | 362 (231-552) |
| Total bilirubin (µmol/L) (median, IQR) | 76 (29-141) |
| INR (median, IQR) | 1.16 (1.04-1.32) |
| Albumin (g/L) (median, IQR) | 34 (30-39) |
ERCP procedural characteristics
Figure 2 provides an overview of procedural characteristics of the 464 ERCPs performed in individuals with PSC. Sphincterotomy was performed in 88 (20%) procedures, while 346 (77%) had evidence of previous sphincterotomy. Balloon dilatation was done in two-thirds of procedures, while stent insertion and removal were done in approximately one-third. Stone and sludge removal was performed in approximately a quarter of the procedures (23% and 26%, respectively). Peroral cholangioscopy was performed in 33 (7.3%). Technical success with good biliary drainage/flow postintervention was reported in 89% of cases. A dominant stricture was reported in 41% of cases, while a relevant stricture was reported in 82% of cases. Target biliary lesion location on ERCP was noted to be in the CBD in 36%, hilar area (CHD, right hepatic, and/or left hepatic) in 34%, and intrahepatic ducts in 3.7%; 26% of cases did not have a specific target area identified.
Figure 2.
Endoscopic retrograde cholangiopancreatography (ERCP) procedural details in patients with primary sclerosing cholangitis (PSC).
Factors associated with stent insertion
Stent insertion was associated with increasing age, high total bilirubin or creatinine, jaundice, concern for malignancy, and/or previous stent insertion (Figure 3). Stent insertion was inversely associated with being on UDCA (OR 0.64, CI 0.43-0.97).
Figure 3.
Univariate analysis of factors associated with stent insertion.
Biochemical changes peri-procedure
There was a trend towards decreasing total bilirubin post-ERCP after stent insertion or balloon dilatation, although this was not significant (P = .31 and P = .074, respectively) (Figure S1). Similarly, there was no significant change in ALP with stent insertion (P = .13), nor with balloon dilatation (P = .74). Although there was a trend towards total bilirubin decline and stabilization of ALP post-ERCP in those without cirrhosis, this was not statistically significant (P = .98 and P = .22 for total bilirubin and ALP, respectively).
Pathology results
Biliary brushings, aspirate, and bile duct biopsies were collected from 163 (36%), 37 (8.1%), and 46 (10%) of ERCPs, respectively. Of all satisfactory cytology samples (n = 167), 86% had reactive/inflammatory cells, while 20% were suspicious for neoplasm with dysplastic/malignant cells detected. Of all satisfactory biopsies (n = 45), 76% revealed reactive/inflammatory cells, while 27% were suspicious for neoplasm with dysplastic/malignant cells detected. Upon review of the clinical and procedural characteristics relating to procedures that yielded neoplastic (n = 40 ERCPs from 32 patients) versus nonneoplastic pathology (n = 148 ERCPs from 89 patients), there were no significant differences found in terms of age at ERCP, duration of known PSC diagnosis, sex, or concurrent IBD (Table S1). There were also no significant associations between report of a dominant or relevant stricture and finding neoplastic pathology. Use of UDCA and clinical cirrhosis diagnosed was less in those with neoplastic pathology (25% vs 51%, P = .005; 27% vs 48%, P = .036, respectively). Concern for malignancy was noted to be a more common ERCP indication in cases that ultimately had neoplastic pathology (65% vs 30%, P < .001); however, there were no distinct differences in symptomatology prior to procedure associated with neoplastic versus nonneoplastic pathology. There was increased stent insertion in cases associated with neoplastic pathology (57% vs 30%, P = .002) and less balloon dilatation (52% vs 89%, P < .001). While there was a trend toward more hilar target biliary lesions at ERCP noted with neoplastic pathology (58%), this was not statistically significantly different from the distribution of target lesion locations associated with nonneoplastic pathology.
Post-ERCP complications
There were 423 ERCP procedures with data retrieved regarding postprocedural complications within 90 days. Development of any post-ERCP complication was described in 127 procedures (30%). The most common complications were biliary obstruction/blockage (22%), post-ERCP cholangitis (15%), stent failure (8.9%), and post-ERCP pancreatitis (3.3%). Cholecystitis occurred in 4 individuals, 2 had perforation or leak, 1 developed respiratory complications, and there were 5 reported deaths within 90 days of procedure. One-third (34%) of procedures were followed by a repeat ERCP (performed at the same or a different therapeutic endoscopy centre) within 90 days. Notably, stent failure was significantly higher in those with neoplastic pathology (24%) compared to those without neoplastic pathology (6.1%) (P = .005). No other post-ERCP complication was significantly different between procedures with neoplastic versus nonneoplastic pathology.
With univariate analysis, developing any ERCP complication was associated with preprocedural symptoms of subjective fevers, abdominal pain, jaundice, as well as endoscopically active IBD at the time of ERCP (Table 2). Procedural factors associated with complications included presence of a relevant stricture, having a target lesion location, stent insertion, or stones removed. Pruritus, use of UDCA, presence of cirrhosis, presence of a dominant stricture, duration of PSC, age at ERCP, stent removal, balloon dilatation, sludge removal, or technical success at end of procedure were not associated with complications. The association between stent insertion and 90-day complications remained statistically significant on multivariable analyses with at least a 3-fold increased risk (Table 2).
Table 2.
Univariate and multivariable analysis of risk factors associated with 90-day postprocedural complications.
| Variable | Univariate analysis | Multivariable analysis |
||
|---|---|---|---|---|
| OR (95% CI) | aOR (95% CI) | aOR (95% CI) | aOR (95% CI) | |
| Male sex | 1.45 (0.90-2.37) | 1.82 (0.62-5.40) | 1.44 (0.47-4.40) | 1.09 (0.45-2.61) |
| Age at ERCP | 0.99 (0.98-1.01) | 1.00 (0.97-1.04) | 1.00 (0.97-1.04) | 1.00 (0.97-1.02) |
| IBD endoscopically active at ERCP | 2.21 (1.19-4.09) | 3.82 (1.12-13.0) | 3.17 (0.90-11.1) | - |
| Subjective fever | 1.62 (1.03-2.53) | 1.04 (0.47-2.28) | 1.28 (0.57-2.90) | 1.34 (0.68-2.65) |
| Abdominal pain | 2.16 (1.41-3.33) | 1.64 (0.72-3.72) | 1.76 (0.74-4.22) | 1.37 (0.66-2.85) |
| Jaundice | 1.72 (1.12-2.69) | 1.60 (0.74-3.42) | - | - |
| Log (total bilirubin) | - | - | 1.07 (0.72-1.59) | 0.96 (0.69-1.33) |
| Relevant stricture present | 2.30 (1.24-4.58) | 1.59 (0.65-8.91) | 1.23 (0.21-7.31) | 2.18 (0.59-8.01) |
Target location (vs none)
|
|
|
|
|
| Stent insertion | 2.35 (1.52-3.62) | 4.06 (1.73-9.51) | 3.10 (1.22-7.81) | 3.02 (1.47-6.23) |
| Stone removal | 1.66 (1.03-2.65) | 1.51 (0.64-3.56) | 1.05 (0.42-2.60) | 1.22 (0.55-2.71) |
Discussion
In this retrospective study, we analyze the clinical, procedural, and pathological features of PSC patients undergoing ERCP at a high-volume centre. Key findings include the characteristics of patients referred for ERCP, intraprocedural interventions, technical success rates in PSC-ERCP, rates of neoplastic pathology, and post-ERCP complications.
Individuals with PSC undergoing ERCP tend to have high disease burden, as confirmed by our study where the majority presented with evidence of biliary obstruction (high total bilirubin and/or ALP). Most studies relating to PSC-ERCP focus on endoscopic management of dominant strictures, which recognizably can be major sources of obstruction, infection, and cholangioncarcinoma.14 Studies quote significant improvement of jaundice, pruritus, and short-term transplant-free survival postendoscopic management of such lesions.15,16 Nevertheless, the benefit of ERCP in PSC remains unclear. For instance, in our study, there was a decrease in total bilirubin after stent insertion or balloon dilatation, yet this was not statistically significant. Furthermore, total bilirubin tended to decline in those without cirrhosis but remained stable despite endoscopic intervention in those with cirrhosis, suggesting that ERCP may have limited role in those with advanced biliary disease and/or liver dysfunction. In addition, it remains challenging to interpret literature data due to varying definitions of “dominant stricture” and the biased nature of small cohort studies. This can be noted by varying proportions of cohorts with dominant strictures, with 41% of ERCPs in our cohort compared to 63% of patients in another large retrospective cohort of PSC-ERCP.8 The definition lacks accounting for biochemical or clinical characteristics associated with the stricture. Furthermore, the mean survival of PSC individuals with dominant strictures is significantly lower than those without (13.7 years vs 23 years in 1 study), with the difference due primarily to development of cholangiocarcinoma being higher in those with dominant strictures.
In our study cohort, one-fifth of PSC-ERCPs with satisfactory pathology demonstrated concerns for neoplasm (dysplasia and/or malignancy). Given the significantly elevated risk of cholangiocarcinoma in PSC, it is vital that intraductal sampling be done to evaluate for possible malignancy. Brush cytology has been a longstanding method of evaluation, although has poor sensitivity in diagnosing biliary malignancy, particularly in the absence of cellularity and fibrosis.17 Addition of intraductal biopsies may improve sensitivity to 59%, while technologies such as fluorescence in situ hybridization or next-generation sequencing can improve sensitivity for diagnosing biliary high-risk neoplasia and malignancy to 76%-85% without compromising specificity (90%).18 In the future, use of cholangioscopy may add clinical utility to diagnosing malignant versus benign strictures.19 Currently, these modalities are not widespread, however, continue to be expanded in terms of use and may add to diagnostic utility of ERCP in PSC. Known risk factors for cholangiocarcinoma amongst those with PSC include duration of IBD prior20 and presence of a dominant stricture.14 Concerningly, our results concluded that symptomatology was not significantly different between those with neoplastic and nonneoplastic pathology. Furthermore, while suspicion for malignancy was a common indication for procedures with neoplastic pathology, one-third of procedures with such an indication were nonneoplastic, and one-third of procedures without suspicion for malignancy demonstrated neoplastic pathology. Moreover, neoplastic pathology was not positively correlated with a clinical diagnosis of cirrhosis. These results exemplify the huge unmet need for accessible, noninvasive cholangiocarcinoma screening mechanisms amongst PSC individuals. While no universal screening recommendations have been made, scheduled imaging has been associated with improved survival in PSC individuals through earlier tumour detection and evaluation of biliary strictures.9 Notably, in our practice, ERCP and intraprocedural pathology is done on-demand in response to clinical symptoms, rather than regularly scheduled endoscopic dilatation of high-grade biliary strictures as seen in another retrospective cohort study conducted in Germany. Notably, this study reported transplant-free survival benefit only in those with initial or later development of a dominant stricture.8 Interestingly, neoplastic pathology was also detected in those without a target lesion or dominant stricture in our cohort. Whether there is added benefit from regular ERCP with intraductal sampling as part of a biliary malignancy screening paradigm remains to be evaluated in future studies. Lastly, the role of CA19-9 levels also remains inconclusive.
In comparison to previous studies, post-ERCP cholangitis rates were comparable to the general population at 15%, reflecting similar reported rates at high-volume endoscopy centres.6,21 Similarly, post-ERCP pancreatitis rates (3.4%) were congruent with rates seen in non-PSC patients.6,7 Notably, stent insertion was associated with higher risk of complications within 90 days even with adjusting for other clinical features, reflecting the literature.22-24 A previous trial has also suggested no superiority of short-term stenting compared to balloon dilatation in terms of recurrence-free rate of the primary dominant stricture, although stenting tended to be associated with treatment-related adverse events, including pancreatitis and cholangitis.24 Of note, our population had significant differences from this study, such as including those with prior stenting or ERCP in the months prior, bacterial cholangitis, and/or suspicion for malignancy. Furthermore, real-world practice in our centre involves clinical judgement in the decision to stent a biliary lesion, as demonstrated by our results associating stent insertion with a sicker PSC phenotype and suspicion for malignancy. Stent failure was also associated with neoplastic pathology. It is unclear if stent insertion has a direct (causative) effect or an associative relationship with post-ERCP complication risk. In other studies, performing biliary sphincterotomy and passage of a guidewire into the pancreatic duct was associated with post-ERCP complications, although this finding was not replicated in our cohort. Centralization of PSC-ERCP at specialized centres may help with reducing complication rates, as PSC-ERCP is associated with an additive risk of adverse events on top of usual ERCP risk.6
This study is limited due to its single-centre retrospective nature and referral bias given the centre’s quaternary referral basis. Furthermore, there is data missingness with regard to biochemistry, ERCPs done at other institutions, and postprocedural outcomes. Due to the multicentre healthcare utilization of individuals with PSC in our region, such knowledge gaps may be addressed in future studies on a larger multicentre scale by leveraging provincial healthcare administrative data. Lastly, only 5% of procedures were performed in patients listed for liver transplant in this study, and thus results may have limited applicability to individuals with advanced or decompensated liver disease. Future studies are required to detail the disease trajectory and circumstances under which PSC patients will derive the most benefit from ERCP with the lowest risk of complications.
In summary, PSC patients undergoing ERCP have high symptom burden and rates of neoplastic pathology. They may have high rates of post-ERCP biliary obstruction but comparable rates of cholangitis and pancreatitis to the general population undergoing ERCP. Stent insertion at ERCP was associated with a sicker PSC phenotype with more biliary obstruction and malignancy concern, which may explain why stent insertion is associated with a 3-fold risk of post-ERCP complications within 90 days. Future studies involving multicentre data may address knowledge gaps regarding the role of ERCP in altering PSC disease trajectory.
Supplementary Material
Contributor Information
Kristel K Leung, The Autoimmune and Rare Liver Disease Programme, Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, Ontario, M5G 2C4, Canada; Division of Gastroenterology, Department of Medicine, Queen’s University, Kingston, Ontario, K7L 3N6, Canada.
Michael Youssef, The Autoimmune and Rare Liver Disease Programme, Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, Ontario, M5G 2C4, Canada.
Yasi Xiao, Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, 19107, United States.
Catherine Streutker, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A1, Canada; Division of Gastroenterology and Hepatology, St. Michael’s Hospital, Toronto, Ontario, M5B 1W8, Canada.
Aliya Gulamhusein, The Autoimmune and Rare Liver Disease Programme, Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, Ontario, M5G 2C4, Canada.
Bettina Hansen, Erasmus Medical Centre, Rotterdam, 3015 GD, Netherlands; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, M5S 1A1, Canada.
Natalia Calo, Division of Gastroenterology and Hepatology, St. Michael’s Hospital, Toronto, Ontario, M5B 1W8, Canada.
Gary May, Division of Gastroenterology and Hepatology, St. Michael’s Hospital, Toronto, Ontario, M5B 1W8, Canada.
Jeffrey Mosko, Division of Gastroenterology and Hepatology, St. Michael’s Hospital, Toronto, Ontario, M5B 1W8, Canada.
Gideon M Hirschfield, The Autoimmune and Rare Liver Disease Programme, Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, Ontario, M5G 2C4, Canada.
Author contributions
All authors contributed to study conception, design, and/or data collection. Kristel K. Leung, Michael Youssef, and Yasi Xiao conducted chart review and abstracted relevant data. Kristel K. Leung and Bettina Hansen conducted statistical analyses. Kristel K. Leung and Michael Youssef drafted the manuscript. All authors provided critical appraisal, reviewed and approved the final version of the manuscript.
Supplementary material
Supplementary material is available at Journal of the Canadian Association of Gastroenterology online.
Funding
None declared.
Conflicts of interest
Conflict of interest disclosure forms (ICMJE) have been collected for all co-authors and can be accessed as supplementary material here.
Data availability
Data supporting the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data supporting the findings of this study are available from the corresponding author upon reasonable request.