In individuals undergoing total pancreatectomy, an additional islet autotransplantation (total pancreatectomy with islet autotransplantation [TPIAT]) can be performed. We investigated the degree to which islet secretory function is preserved after TPIAT and assessed the relation to glycaemic control using continuous glucose monitoring. Eligibility for TPIAT was assessed by a multidisciplinary team. The cohort consisted of all individuals undergoing TPIAT from 2014 to 2024. To assess islet secretory function, participants were subjected to a 2 h liquid meal stimulation test prior to TPIAT, at 3 months and annually post TPIAT. Glycaemic control was assessed using continuous glucose monitoring and HbA1c. Twenty-six individuals were included, of whom 88.5
BACKGROUND:Although ursodeoxycholic acid (UDCA) is commonly prescribed for primary sclerosing cholangitis (PSC), a beneficial long-term effect on solid clinical endpoints has not yet been established. This study evaluated the efficacy of UDCA on long-term transplant-free survival in a longitudinal population-based cohort. METHODS:We conducted a retro/prospective study between January 2008 and August 2020, using data from the Dutch population-based EpiPSC2 cohort. Medication use was collected through medical chart review, periodic questionnaires, and the national pharmacy prescription database. The effect of UDCA use was assessed as time-dependent variable using a Cox proportional hazards model. Sex, age at diagnosis, PSC type, IBD status, transplant center inclusion, and PSC diagnosis year were considered as covariates. RESULTS:Medication data were available for 739 cases. Individuals with uncertain use of UDCA were excluded, resulting in a study population of 527. No discernable effect of UDCA use was observed on the endpoints liver transplantation (LT)/all-cause mortality [adjusted HR 1.13 (95%CI 0.76-1.67)] nor LT/PSC-related death/occurrence of hepatobiliary malignancy [adjusted HR 1.07 (95%CI 0.71-1.60)]. The HR of UDCA use was numerically reduced for hepatobiliary malignancy [0.68 (95%CI 0.34-1.37)]. CONCLUSION:Our study failed to demonstrate that UDCA use impacts long-term outcomes in patients with PSC.
BACKGROUND:There is a paucity of data on the cost-utility of endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) compared with surgical gastrojejunostomy (SGJ) as palliative treatment of malignant gastric outlet obstruction. METHODS:In the ENDURO trial, 98 patients with malignant gastric outlet obstruction from 12 Dutch hospitals were randomized between EUS-GE (N = 48) and SGJ (N = 50). Cost utility was evaluated from a healthcare perspective with a time horizon of 1 month. A bottom-up approach was used to calculate the costs of each intervention, including the per-minute price of the endoscopy and operating room (OR), considering personnel, construction, inventory and overhead costs. Other in-hospital costs were calculated using insurance claim data. Effectiveness was displayed as quality-adjusted life years (QALY). Bootstrapping was performed to estimate uncertainty. RESULTS:The calculated per-minute price for the endoscopy room was €8.64 (US $9.34). The per-minute price for an OR was €11.78 (US $12.74). The mean intervention costs were estimated at €4405.40 (US $4762.68) for EUS-GE and €3393.71 (US $3668.93) for SGJ. Mean total in-hospital costs were lower following EUS-GE (€5172 [US $5591]) than after SGJ (€10,458 [US $11,306]), mainly due to a shorter length of hospital stay following EUS-GE. Bootstrapping showed that 99.9% of iterations resulted in lower costs for EUS-GE. Mean difference in 1-month QALY contribution was 0.004 in favor of EUS-GE. Most iterations fall within the bottom right quadrant (95.6%) of the cost-effectiveness plane, indicating lower costs and improved QALY contribution for EUS-GE. DISCUSSION:In this study, EUS-GE was more cost effective than SGJ. The additional intervention costs were clearly outweighed by a decrease in in-hospital costs after the procedure.
Acute cholangitis is an infection of the biliary tract that is managed with adequate biliary drainage combined with antibiotic treatment. The international Tokyo Guidelines 2018 recommend 4 to 7 days of antibiotic treatment after adequate biliary drainage, but observational data suggest shorter treatment may be sufficient. We assessed whether 1 day of antibiotic treatment is non-inferior to 4–7 days of antibiotic treatment for acute cholangitis after adequate biliary drainage. The COBRA-trial is a multicentre, open-label, parallel group randomized controlled non-inferiority trial with blinded outcome assessment. A total of 416 patients with acute cholangitis will be randomly assigned in a 1:1 ratio to the intervention group (1 day of antibiotic treatment after adequate biliary drainage) or to the control group (4–7 days of antibiotic treatment after adequate biliary drainage). Patients with acute cholangitis due to common bile duct stones, benign or malignant distal biliary obstruction, or distal biliary stent dysfunction are eligible. Randomization will take place once adequate biliary drainage is achieved by ERCP. Main exclusion criteria are concomitant pancreatitis, liver abscess, cholecystitis, and another infectious diagnosis at the time of randomization, use of systemic maintenance antibiotics, and specific immunosuppressants. Patients will be stratified for blood culture results at the time of randomization and aetiology of cholangitis. The primary endpoint is clinical cure, defined as the patient being symptom-free by day 14, with no relapse or death occurring by day 30. Secondary endpoints include 30-day and 90-day all-cause mortality, relapse of cholangitis by day 90, time from ERCP to first relapse, any other subsequent infection requiring antibiotic treatment within 90 days, duration of initial hospital stay, number of days treated with antibiotics by day 30, subsequent infections with multidrug resistant (MDR) bacteria, quality of life, and cost-effectiveness. This trial assesses whether a short course of antibiotic treatment for acute cholangitis is as safe and effective compared to a longer course of antibiotic treatment. If confirmed, the results could substantially reduce antibiotic exposure and healthcare resource utilization, thereby contributing to global efforts to minimize unnecessary antibiotic treatment. ClinicalTrials.gov NCT05750966, registered on March 2nd, 2023.
Background Endoscopic ultrasound-guided hepatico-gastrostomy (EUS-HGS) enables internal biliary drainage via the stomach in patients with altered anatomy, inadequate left hepatic duct drainage, or duodenal obstruction. The technically demanding procedure is only performed at expert centers in the Netherlands. Most available evidence originates from selected cohorts, overestimating real-world outcomes. We evaluated outcomes of EUS-HGS in a nationwide cohort. Methods This nationwide retrospective cohort study included all patients in the Netherlands who underwent EUS-HGS attempts between 2009 and 2025, outside of prospective studies. The primary outcome was technical success. Secondary outcomes included clinical success, complications, time to recurrent biliary obstruction (RBO), and overall survival. Results A total of 107 procedures in 105 patients were analyzed (median age: 68 years [IQR: 59-76]; 55%: male). Technical success was achieved in 77% (81/105). Failures were due to absence of a safe puncture tract (n = 7), unsuccessful bile duct puncture (n = 3), inability to achieve deep guidewire insertion (n = 3), failed fistula formation (n = 3), or unsuccessful or non-attempted stent placement (n = 7). Clinical success occurred in 78% of technically successful cases (63/81), corresponding to 60% in intention-to-treat analysis (63/105). Procedural complications occurred in 16/107 (15%), and postprocedural complications in 17/107 (16%). One procedure-related death occurred. RBO occurred in 28% (23/81) during a median follow-up of 61 days [IQR: 23-131]. Median overall survival was 91 days [IQR: 66-155]. Conclusion In this nationwide real-world cohort, technical and clinical success rates of EUS-HGS were modest compared with selected expert series, underscoring the need for prospective studies to improve patient selection, stent strategies, and procedural safety.
Background and study aims It is currently unclear whether obstruction location affects clinical and procedure outcomes after endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) with a lumen-apposing metal stent (LAMS) in patients with malignant gastric outlet obstruction (GOO). Therefore, we compared clinical outcomes of EUS-GE for malignant GOO located in the stomach with obstruction located in the duodenum. Patients and methods In this nationwide, multicenter, retrospective study, we included consecutive patients who underwent EUS-GE as palliative treatment for malignant GOO. Main outcomes were clinical success, serious adverse events (SAEs) recurrence of obstructive symptoms, and LAMS dysfunction. Results Between 2018 and 2023, 298 patients underwent EUS-GE. Clinical success was achieved in 73 of 82 patients with a gastric obstruction (94%) and in 174 of 216 patients with a duodenal obstruction (87%). No association was found between location of obstruction and clinical success (odds ratio [OR] 2.62, 95% confidence interval [CI] 0.91 to 7.52, P = 0.073) or SAEs (OR 0.26, 95% CI 0.06 to 1.20, P = 0.083). Recurrent obstructive symptoms occurred more frequently in patients with a gastric obstruction (hazard ratio 1.74, 95% CI 1.09 to 2.77, P = 0.020). LAMS dysfunction did not differ between the groups (7 patients [9%] with a gastric obstruction and 11 patients [5%] with a duodenal obstruction). Conclusions In this study, EUS-GE in patients with a gastric obstruction had comparable technical and clinical efficacy and a similar safety profile to EUS-GE for duodenal obstruction. However, gastric obstruction was associated with recurrent symptoms of obstruction unrelated to LAMS dysfunction.
Background Preoperative endoscopic biliary drainage may lead to complications (16%-24%), potentially hampering surgical exploration. Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) may reduce drainage-related complications, however it is unknown whether EUS-CDS could in itself hamper surgical exploration as series with surgeon reported outcomes are lacking. Aim is to assess the impact of preoperative EUS-CDS on pancreatoduodenectomy. Method Consecutive patients who underwent pancreatoduodenectomy after preoperative biliary drainage were included in all eight centers that performed EUS-CDS in the mandatory Dutch Pancreatic Cancer Audit (Jan 2020-Dec 2022). Primary outcome was major postoperative complications. Secondary outcomes included bile leak grade B/C, postoperative pancreatic fistula (POPF) grade B/C, and overall postoperative complications. A propensity score matching (1:3) analysis was performed. Surgeons who performed a pancreatoduodenectomy after EUS-CDS were asked to complete a survey. Results Overall, 937 patients with pancreatoduodenectomy after preoperative biliary drainage were included (42 EUS-CDS, 895 ERCP). Major postoperative complications occurred in eight patients (19%) in the EUS-CDS group and 292 patients (33%) in the ERCP group (RR 0.50; 95%CI, 0.23-1.07). No significant differences were observed in overall complications (RR 0.95; 95%CI, 0.51-1.76), bile leak (RR 1.25; 95%CI, 0.31-4.98) or POPF (RR 0.62; 95%CI, 0.25-1.56). Results were similar after matching. The survey was completed for 29 pancreatoduodenectomies; surgery was not (n=13, 45%), ‘slightly’ (n=8, 28%), ‘clearly’ (n=5, 17%) or ‘severely’ (n=2, 7%) more complex because of the EUS-CDS. Conclusion This early experience suggests that preoperative biliary drainage with EUS-CDS does not increase the rate of complications after pancreatoduodenectomy and only infrequently hampers surgical exploration.
BACKGROUND AND AIM:Direct cholangioscopy and pancreatoscopy have become widely implemented techniques in the diagnostic and therapeutic algorithms of several pancreaticobiliary disorders. This study aimed to generate general and indication-specific European consensus recommendations on cholangioscopy and pancreatoscopy. METHODS:Supported by the available literature, statements were formulated and grouped into the following categories: (1) pre-procedural considerations, (2) general technical aspects, (3) biliopancreatic stones, (4) biliary strictures, and (5) other indications. The evidence level of each statement was determined using the GRADE methodology. Cholangioscopy experts were invited to participate in a modified Delphi process. When 80% consensus was not reached, the statement was modified based on expert feedback and subjected to an additional Delphi round. Statements were rejected if they failed to reach consensus after three Delphi rounds. RESULTS:Thirty cholangioscopy experts completed the Delphi process. Forty-two (97.6%) generated statements were accepted, of which 39 (92.9%) in the first Delphi round. 12 statements on preprocedural and periprocedural settings, 8 statements on biliopancreatic stones, 13 statements on biliary strictures, and 9 statements on other indications were accepted. CONCLUSION:Using a modified Delphi process, we developed general and indication-specific consensus recommendations for cholangioscopy to guide clinical practice.
BACKGROUND:In patients with malignant gastric outlet obstruction, endoscopic ultrasonography-guided gastroenterostomy might be superior to surgical gastroenterostomy, but randomised trials are scarce. We aimed to assess time to resumption of oral intake and the rate of persistent or recurrent obstructive symptoms requiring re-intervention following endoscopic ultrasonography-guided gastroenterostomy compared with surgical gastroenterostomy. METHODS:ENDURO was a multicentre, randomised controlled trial conducted at 12 Dutch academic and teaching hospitals. Hospitals with experience in at least 20 LAMS placements of any indication, at least ten endoscopic gastroenterostomies, and approved competence were eligible to perform endoscopic gastroenterostomy independently within the trial. Adults aged 18 years and older with symptomatic, malignant gastric outlet obstruction in a palliative setting were randomly assigned (1:1) to endoscopic or surgical gastroenterostomy. Randomisation was performed with an electronic data capture system using randomly generated permuted blocks of 2 and 4 and stratified by WHO performance status (0-1 and 2-3). The first coprimary outcome was time to resumption of solid oral intake (Gastric Outlet Obstruction Scoring System score ≥2). The second coprimary outcome was non-inferiority for persistent or recurrent obstructive symptoms requiring re-intervention. The predefined non-inferiority margin of the risk difference was 20%. All outcomes were analysed in all randomly assigned participants. This trial was registered in the International Clinical Trials Registry Platform, NL9592, and is completed. FINDINGS:Between Feb 18, 2022, and Feb 26, 2024, 250 patients were screened, 98 of whom were randomly assigned to endoscopic gastroenterostomy (n=48) or surgical gastroenterostomy (n=50). 43 (44%) patients were female and 55 (56%) were male. Endoscopic gastroenterostomy had a shorter time to solid oral intake than surgical gastroenterostomy (median 1 day [IQR 1-3] vs 3 days [1-6], hazard ratio 2·21 [95% CI 1·43-3·42]; p=0·0003). Endoscopic gastroenterostomy was non-inferior to surgical gastroenterostomy for persistent or recurrent obstructive symptoms requiring re-intervention (five [10%] vs six [12%], risk difference 1·6% [upper limit of 90% CI 8·9]). Overall adverse events were reported in 28 (58%) patients in the endoscopic gastroenterostomy group and 32 (64%) in the surgical gastroenterostomy group (relative risk 0·91 [95% CI 0·66-1·25]). One fatal event occurred in the endoscopic gastroenterostomy group and three fatal events occurred in the surgical gastroenterostomy group. INTERPRETATION:In patients with malignant gastric outlet obstruction, palliative treatment with endoscopic gastroenterostomy was superior to surgical gastroenterostomy for time to resumption of solid oral intake and was non-inferior for the rate of persistent or recurrent obstructive symptoms requiring re-intervention. Based on these results, endoscopic gastroenterostomy should be the preferred palliative treatment for patients with malignant gastric outlet obstruction. FUNDING:KWF Dutch Cancer Society.
OBJECTIVES:Endoscopic retrograde cholangiopancreatography (ERCP) is frequently indicated in patients who underwent Roux-en-Y gastric bypass (RYGB) surgery. Endoscopic ultrasound-directed ERCP (EDGE) is a technique that is used to create a gastro-gastrostomy by placing a lumen-apposing metal stent (LAMS) between the gastric pouch and the excluded stomach, facilitating subsequent ERCP. However, prospective studies on EDGE are lacking. The aim of this study is to provide prospective evidence for the efficacy and safety of EDGE, including fistula closure. METHODS:This multicenter prospective cohort study included patients scheduled for elective ERCP after RYGB surgery. EDGE was performed as a two-step procedure. The primary endpoint was overall technical success. Secondary endpoints were the technical success of LAMS placement and ERCP individually, persistent fistula, and adverse events (AEs). RESULTS:Between January 2021 and August 2024, 26 patients were included in four Dutch hospitals. Overall technical success was achieved in 25/26 patients (96.2%). Median LAMS indwelling time was 14 days [IQR 11-28 days]. Two EDGE-related AEs occurred (7.7%): one perforation of the duodenal wall following scope insertion and one bleeding after LAMS placement. Two ERCP-related AEs occurred (7.7%): one CBD perforation and one post-ERCP pancreatitis. Two patients were lost to follow-up. None of the remaining patients had a persistent fistula (0/24). No mortality occurred. CONCLUSIONS:This prospective study shows that two-step EDGE is relatively safe and associated with high technical success, without any cases of a persistent fistula. However, AEs occurred in 4 patients (15.4%), of which two were EDGE-related (7.7%).
Background & Aims:The gut-liver axis is believed to be crucial in the pathogenesis of primary sclerosing cholangitis (PSC). However, the impact of colectomy on liver disease progression is unclear. Our study estimated the effect of colectomy on PSC progression with correction for time dependency and established risk factors by pooling data from several cohorts across different countries. Methods:We analysed data from the International PSC Registry (IPSCR), comprising patients from Finland, The Netherlands, Norway, and Sweden. Primary endpoint was defined as liver transplantation (LT) or PSC-related death. Cox proportional hazards regression onto time-dependent colectomy status, with specification for extent, was performed with adjustment for sex, age at diagnosis, large or small duct PSC, features of autoimmune hepatitis, time-dependent inflammatory bowel disease (IBD) status, centre of inclusion, and country of residence. Results:A total of 3,110 participants were included, of whom 470 (15%) had undergone colectomy. During a total follow-up of 32,236 patient-years, 395 deaths and 653 LTs were observed. Compared with patients with PSC with intact colon, the hazard ratio (HR) of reaching LT or PSC-related death was significantly decreased in patients with proctocolectomy with permanent ileostomy (HR 0.41; 95% CI 0.24-0.71). This effect was less pronounced in case of hemi- or subtotal colectomy (HR 0.81; 95% CI: 0.58-1.12) and not observed for proctocolectomy with pouch (HR 1.00; 95% CI: 0.73-1.38). The reduced risk was mainly associated with a lower rate of LT or death resulting from liver failure (HR 0.24; 0.10-0.53). Conclusions:Proctocolectomy with permanent ileostomy was associated with decreased risk for LT and PSC-related death. These findings support the role of the gut-liver axis in the pathophysiology of PSC and call for consideration in counselling patients who face impending colorectal surgery. Impact and implications:The impact of the gut-liver axis in the pathophysiology of primary sclerosing cholangitis (PSC) has remained uncertain. In this study, proctocolectomy with ileostomy was associated with improved transplant-free survival, defined as a reduced risk of liver transplantation or PSC-related death, indicating that intestinal factors may influence disease progression. These findings are important for clinicians, researchers, and patients as they suggest that surgical management of colonic disease may have prognostic implications in PSC, and for further studies to clarify mechanisms and guide clinical decision-making.
Background Endoscopic retrograde cholangiopancreatography (ERCP) with fully covered self-expandable metal stent (FCSEMS) placement is the preferred approach for biliary drainage in patients with suspected distal malignant biliary obstruction (MBO). However, FCSEMS placement is associated with a high risk of post-ERCP pancreatitis (PEP). Endoscopic sphincterotomy prior to FCSEMS placement may reduce PEP risk. Objective To compare endoscopic sphincterotomy to no sphincterotomy prior to FCSEMS placement. Design This multicentre, randomised, superiority trial was conducted in 17 hospitals and included patients with suspected distal MBO. Patients were randomised during ERCP to receive either endoscopic sphincterotomy (sphincterotomy group) or no sphincterotomy (control group) prior to FCSEMS placement. The primary outcome was PEP within 30 days. Secondary outcomes included procedure-related complications and 30-day mortality. An interim analysis was performed after 50% of patients (n=259) had completed follow-up. Results Between May 2016 and June 2023, 297 patients were included in the intention-to-treat analysis, with 156 in the sphincterotomy group and 141 in the control group. After the interim analysis, the study was terminated prematurely due to futility. PEP did not differ between groups, occurring in 26 patients (17%) in the sphincterotomy group compared with 30 patients (21%) in the control group (relative risk 0.78, 95% CI 0.49 to 1.26, p=0.37). There were no significant differences in bleeding, perforation, cholangitis, cholecystitis or 30-day mortality. Conclusion This trial found that endoscopic sphincterotomy was not superior to no sphincterotomy in reducing PEP in patients with distal MBO. Therefore, there was insufficient evidence to recommend routine endoscopic sphincterotomy prior to FCEMS placement. Trial registration number NL5130.
BACKGROUND:Preoperative endoscopic biliary drainage may lead to complications (16 %-24 %), potentially hampering surgical exploration. Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) may reduce drainage-related complications; however, in the absence of surgeon-reported outcomes, it is unknown whether EUS-CDS may hamper surgical exploration. This study assessed the impact of preoperative EUS-CDS on pancreatoduodenectomy. METHOD:Consecutive patients who underwent pancreatoduodenectomy after preoperative biliary drainage were included in all eight centers performing EUS-CDS in the mandatory Dutch Pancreatic Cancer Audit (Jan 2020-Dec 2022). The primary outcome was major postoperative complications. Secondary outcomes included bile leak grade B/C, postoperative pancreatic fistula (POPF) grade B/C, and overall postoperative complications. A propensity score-matching (1:3) analysis was performed. Surgeons performing pancreatoduodenectomy after EUS-CDS completed a survey on surgical difficulty. RESULTS:937 patients with pancreatoduodenectomy after preoperative biliary drainage were included (42 EUS-CDS, 895 endoscopic retrograde cholangiopancreatography [ERCP]). Major postoperative complications occurred in 8 patients (19.0 %) in the EUS-CDS group and 292 (32.6 %) in the ERCP group (relative risk [RR] 0.50; 95 %CI 0.23-1.07). No significant differences were observed in overall complications (RR 0.95; 95 %CI 0.51-1.76), bile leak (RR 1.25; 95 %CI 0.31-4.98), or POPF (RR 0.62; 95 %CI 0.25-1.56). Results were similar after matching. The survey was completed for 29 pancreatoduodenectomies; surgery was not (13, 45 %), "slightly" (9, 31 %), "clearly" (5,17 %), and "severely" (2, 7 %) more complex because of EUS-CDS. CONCLUSION:This early experience suggests that preoperative biliary drainage with EUS-CDS does not increase the rate of complications after pancreatoduodenectomy and only infrequently hampers surgical exploration.
Abstract Background Inflammatory bowel disease (IBD) in patients with primary sclerosing cholangitis (PSC) is a distinct disease entity requiring specific management1. Data on characterisation of the phenotype of PSC-IBD are limited and subclassification is lacking. Therefore, this study aims to describe the macroscopic and microscopic distribution of IBD in patients with PSC. Methods A retrospective analysis was conducted on data from PSC-IBD patients included in the EpiPSC2 registry, comprising patients from 46 hospitals across the Netherlands. Data on inflammation at macro- and microscopic level in the ileum and 6 colonic segments were collected on every available endoscopy. Data after (hemi)colectomy were excluded. Polytomous latent class analysis was used to identify subgroups of IBD distribution2. First, latent class models (LCM) were fitted on all endoscopic and histologic data and Akaike and Bayesian information criteria were used to determine the optimal number of classes. After random sampling with replacement the LCM with the ideal number of groups was fitted on 20 samples of one endoscopy with inflammation per subject, and the pooled class probability was calculated per subgroup. Results A total of 3177 endoscopies from 522 PSC-IBD patients (median of 5 [IQR 2-9] endoscopies per patient) were included. The maximum depth of insertion was the terminal ileum in 62% and caecum in 27% of endoscopies. Macroscopic inflammation was observed in 1521 (48%) endoscopies from 428 patients. Segmental colon biopsies were obtained during 650 (20%) endoscopies in 237 subjects, and ileum biopsies in 144 (22%) endoscopies in 100 subjects. Microscopic inflammation in any segment was observed in 265 (41%) endoscopies. An LCM with four classes was the best fit to the macro- and microscopic data: no inflammation, right-sided colitis (pooled class probability 36%), left-sided colitis (30%), and pancolitis (34%). In right-sided colitis and pancolitis the probability of ileal involvement was 16% and 22%, whereas left-sided colitis most often displayed an absence of ileal involvement (probability of 4%) [fig.1]. For microscopic inflammation no pooled class probabilities could be calculated due to low sample size. In 139 (21%) endoscopies, LCM showed more extensive inflammation at microscopic assessment as compared to macroscopic assessment. Conclusion Macroscopic and microscopic inflammation in PSC-IBD may be classified into right sided colitis, left sided colitis, and pancolitis. The microscopic extent exceeds macroscopic inflammation in over 20% of endoscopies with segmental biopsies. Future research into the prognostic implication of this subclassification on PSC- and IBD-related outcomes is required. References 1.van Munster KN, Bergquist A, Ponsioen CY. Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two? J Hepatol. 2024;80(1):155-68.2. 2.Lewis J, Linzer D. poLCA: An R Package for Polytomous Variable Latent Class Analysis. Journal of Statistical Software. 2011;42