The Effect of Immunsuppressive Treatment Agents on Post-ERCP Pancreatitis in Living Donor Liver Transplant Patients

The Effect of Immunsuppressive Treatment Agents on Post-ERCP Pancreatitis in Living Donor Liver Transplant Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Effect of Immunsuppressive Treatment Agents on Post-ERCP Pancreatitis in Living Donor Liver Transplant Patients Gülşah YAMANCAN, Jehat Kılıç, Sedat Çiçek, Sami Akbulut, Yılmaz Bilgiç This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8661362/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Introduction: Liver transplantation is now routine for end-stage liver disease, but biliary complications occur in ~ 5–30% of recipients. Endoscopic retrograde cholangio-pancreatography (ERCP) has become the gold standard for managing these issues, yet post-ERCP pancreatitis (PEP) remains the most common adverse event, and its risk factors in transplant patients are not well defined. We aimed to identify predictors of PEP in liver transplant recipients, with a specific focus on the association between immunosuppressive therapy and PEP. Materials and Methods. This single-center retrospective cohort included 1,338 liver-transplant recipients who subsequently underwent ERCP. The following variables were extracted from the medical record: age, sex, transplant etiology; type of biliary anastomosis at transplantation (duct-to-duct vs Roux-en-Y hepaticojejunostomy); prior endoscopic sphincterotomy (EST); use of pre-cut (needle-knife) sphincterotomy at the index ERCP; placement of a common bile duct stent; maintenance immunosuppressive regimen; post-procedure antibiotic use; ERCP indication; number of ERCP sessions; and occurrence of PEP. A multivariable logistic-regression analysis was perfomed to identify determinants of PEP. Results A total of 1,338 liver transplant recipients who underwent ERCP were screened, of whom 274 patients with complete clinical and follow-up data were included in the final analysis, comprising 1,174 ERCP sessions. Post-ERCP pancreatitis (PEP) occurred in 66 patients, yielding an overall incidence of 5.6%. Age, sex, graft lobe, biliary anastomosis type, stent placement, and maintenance immunosuppressive regimen were not associated with PEP (all p > 0.05). Precut sphincterotomy was significantly more frequent among patients who developed PEP and was independently associated with increased risk in multivariable analysis (adjusted OR 2.72, 95% CI 1.37–5.42; p = 0.004). In contrast, a history of prior endoscopic sphincterotomy was independently protective (adjusted OR 0.43, 95% CI 0.22–0.84; p = 0.013). Conclusion Post-ERCP pancreatitis occurred in about 5% of liver transplant recipients in this cohort. Precut sphincterotomy significantly increased the risk, while prior endoscopic sphincterotomy appeared protective. Immunosuppressive therapy was not associated with pancreatitis risk. These findings highlight that procedural factors, rather than immunosuppressive agents, are the main drivers of post-ERCP pancreatitis in this population and emphasize the need for careful cannulation techniques. Liver Transplantation Endoscopic Retrograde Cholangiopancreatography Post-ERCP Pancreatitis Immunosuppression Figures Figure 1 INTRODUCTION Liver transplantation is now a widely used and effective therapy for end-stage liver disease, with modern surgery and immunosuppression improving outcomes substantially ( 1 ). Biliary complications, however, remain common (≈ 10–30%) and are seen more frequently after living-donor transplants where multiple ductal anastomoses are required ( 1 , 3 ). Well-described risk factors for anastomotic or non-anastomotic strictures include technical issues, prolonged cold/warm ischemia, older donor age, and hepatic artery thrombosis/ischemia ( 3 , 4 ). For most biliary complications, endoscopic therapy—principally ERCP with sphincterotomy, dilation, and stenting—has largely supplanted surgery as first-line management ( 2 , 4 ). ERCP is the cornerstone of managing benign biliary strictures after liver transplantation. PEP is the most frequent ERCP-related adverse event, occurring in roughly 2–10% of unselected cases and up to ~ 20–24% in high-risk settings ( 5 – 7 ). Most episodes are mild, but a minority progress to moderately severe or severe disease and can be fatal; overall mortality is low but higher in severe cases ( 6 ). Randomized and guideline evidence support effective prophylaxis—particularly rectal NSAIDs for nearly all patients and pancreatic-duct stenting in selected high-risk cannulations ( 6 – 9 ). PEP is multifactorial. The initiating event is thought to be early acinar-cell injury with premature intrapancreatic trypsin activation, which triggers a sterile inflammatory cascade. Procedure-related contributors include mechanical trauma to the papilla/pancreatic duct from repeated or difficult cannulation and guidewire passage; hydrostatic over-distension from contrast injection; thermal/diathermic injury during (pre-cut) sphincterotomy; and transient papillary edema or spasm causing outflow obstruction. These insults are amplified in susceptible hosts (e.g., prior PEP, suspected sphincter of Oddi dysfunction, female sex), and can be modulated by local microbial contamination and patient biology. Together, these factors raise ductal pressure, promote zymogen activation, and propagate local and systemic inflammation. [7,10] Because PEP is the most frequent major adverse event after ERCP and is not uncommon in liver-transplant recipients, our primary objectives were to estimate the incidence of PEP in this population, identify procedure- and patient-related risk factors, and examine, in particular, the association between specific immunosuppressive agents and PEP. MATERIAL METHODS This single-center, retrospective clinical study included 1,338 liver-transplant recipients who underwent ERCP at the Department of Gastroenterology, İnönü University School of Medicine, between January 2012 and February 2020. Patient data were extracted from the Turgut Özal Medical Center archives. The study was conducted retrospectively after approval by the İnönü University Ethics Committee (Data: 29/09/2020, decision no. 2020/1060). Study description and patient selection All liver transplant recipients who underwent ERCP at our center between January 2012 and February 2020 were initially reviewed (n = 1,338). Patients were excluded if ERCP or follow-up information was incomplete, if essential clinical or laboratory data required to assess PEP were missing, or if the procedure was non-biliary or technically unsuccessful. After these exclusions, 274 patients with complete and reliable datasets remained and constituted the final study cohort. In this group, a total of 1,174 ERCP sessions were analyzed. For each included patient, relevant demographic, clinical, procedural, and treatment-related information was retrospectively collected from electronic medical records. Extracted variables included age and sex; the indication for liver transplantation; the type of biliary anastomosis performed at transplantation (duct-to-duct or Roux-en-Y hepaticojejunostomy); history of prior endoscopic sphincterotomy (EST); use of pre-cut (needle-knife) sphincterotomy during ERCP; placement of a common bile duct stent; the maintenance immunosuppressive regimen at the time of ERCP; administration of post-procedure antibiotics; the indication for ERCP; and the total number of ERCP sessions per patient. The occurrence of PEP was assessed at the patient level and served as the primary outcome of the study (Fig. 1 ). Definition of PEP : PEP was diagnosed according to the revised Atlanta criteria, requiring ≥ 2 of the following: (i) new or worsening epigastric pain consistent with acute pancreatitis and necessitating analgesia; (ii) serum amylase and/or lipase > 3× the upper limit of normal at ~ 24 hours after ERCP; (iii) imaging findings on contrast-enhanced abdominal CT compatible with acute pancreatitis ( 11 ). Immunosuppression regimen (center protocol) During the study period, the standard post-transplant regimen at İnönü University Turgut Özal Medical Center Liver Transplant Institute consisted of tacrolimus, everolimus, mycophenolate mofetil (MMF), and prednisolone. An initial dose of methylprednisolone (500 mg or 20 mg/kg) was administered immediately after completion of the hepatic artery anastomosis and tapered postoperatively from 100 mg/day to 5 mg/day; steroids were discontinued at month 3 except in autoimmune liver diseases (autoimmune hepatitis, primary sclerosing cholangitis, or primary biliary cholangitis). Tacrolimus (0.02–0.05 mg/kg/day) and MMF (10–30 mg/kg/day) were initiated on postoperative day 3, with tacrolimus trough targets of 7–10 ng/mL in the first year and 3–5 ng/mL thereafter. In patients who developed renal dysfunction (or calcineurin-inhibitor neurotoxicity), tacrolimus was withheld and switched to everolimus until renal function improved, or the tacrolimus dose was reduced and low-dose everolimus was added. Statistical grouping of immunosuppressants. For risk modeling, immunosuppressive exposure was categorized with priority to tacrolimus and everolimus. Patients not receiving either agent for any reason were grouped as MMF or Other (steroids, sirolimus, or cyclosporine). Statistical Analysis Normality of continuous variables was assessed with the Shapiro–Wilk test and homogeneity of variances with Levene’s test. For two-group comparisons, the independent-samples t test was used when normality was satisfied; otherwise, the Mann–Whitney U test was applied. Categorical variables were compared with the χ² test. To evaluate the diagnostic performance of “number of ERCP sessions” for predicting post-ERCP pancreatitis, receiver operating characteristic (ROC) analysis was performed and ROC curves were plotted. Cut-off values were determined using the Youden index, and sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Risk factors associated with pancreatitis were examined using univariable and multivariable logistic regression (enter method). Statistical significance was set at p < 0.05. All analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). RESULTS Among 274 patients, 92 (33.6%) were female and 182 (66.4%) male. Most procedures involved the right lobe (266, 97.1%) rather than the left (8, 2.9%). The anastomosis was most commonly a stricture (212, 77.4%), with fewer normal (56, 20.4%) or other types (6, 2.2%). Regarding EST, 132 (49.4%) had a previous EST, 69 (25.8%) had EST performed (recorded in history), and 66 (24.7%) had no EST. A precut was done in 58 (21.4%) and not done in 213 (78.6%). Immunosuppressive regimens included tacrolimus in 129 (47.1%), everolimus in 19 (6.9%), tacrolimus + everolimus in 55 (20.1%), mycophenolate mofetil in 16 (5.8%), and prednisolone ± others in 55 (20.1%). Antibiotics were given to 64 (23.4%) while 210 (76.6%) did not receive them. Stents were present in 199 (72.6%) and absent in 75 (27.4%). Pancreatitis occurred in 66 (24.1%) overall and was not observed in 208 (75.9%). Among those evaluated after the first session (n = 66), post-session pancreatitis was observed in 38 (57.5%) and not observed in 28 (42.5%) (Table 1 ). Table 1 Baseline Characteristics and Procedural Details of the Study Cohort Variable Category Count (n) Percentage (%) Gender Female 92 33.6 Male 182 66.4 Lobe Right 266 97.1 Left 8 2.9 Type of anastomosis Stricture 212 77.4 Normal 56 20.4 Other 6 2.2 EST Performed 69 25.8 Had previous EST 132 49.4 Not performed 66 24.7 Precut Done 58 21.4 Not done 213 78.6 Immunosuppressive therapy Tacrolimus 129 47.1 Everolimus 19 6.9 Tacrolimus + Everolimus 55 20.1 Mycophenolate mofetil 16 5.8 Prednisolone + others 55 20.1 Antibiotic use Received antibiotics 64 23.4 Did not receive 210 76.6 Stent Present 199 72.6 Absent 75 27.4 Pancreatitis Observed 66 24.1 Not observed 208 75.9 Post–first session pancreatitis Not observed 28 42.5 Observed 38 57.5 EST : Endoscopic Sphincterotomy, Precut : Precut Sphincterotomy, MMF : Mycophenolate Mofetil, ERCP : Endoscopic Retrograde Cholangiopancreatography Among 266 ERCPs, the most common indication was anastomotic stricture in 200 cases (75.2%). Less frequent indications included bile leak in 21 (7.9%), non-anastomotic stricture in 16 (6.0%), anastomotic stricture with stone in 11 (4.1%), and anastomotic stricture with leak in 10 (3.8%). Normal ERCP findings accounted for 7 procedures (2.6%), and feeding catheter in the common bile duct was the indication in 1 case (0.4%). Overall totals sum to 266 procedures (100%) (Table 2 ). Table 2 Indications for ERCP Indication Count (n) Percentage (%) Anastomotic stricture 200 75.2 Bile leak 21 7.9 Non‑anastomotic stricture 16 6.0 Anastomotic stricture + stone 11 4.1 Anastomotic stricture + leak 10 3.8 Normal ERCP 7 2.6 Feeding catheter in the common bile duct 1 0.4 Total 266 100.0 ERCP : Endoscopic Retrograde Cholangiopancreatography In 274 ERCPs, pancreatitis developed in 66 patients (24.1%). Age and sex did not differ between groups (48.3 ± 15.8 vs 49.2 ± 13.6 years; female 36.4% vs 32.7%; both p > 0.05). Lobe side and anastomosis type were also similar (right lobe 98.5% vs 96.6%; stricture 83.3% vs 75.5%; both p > 0.05). Prior/ongoing EST status differed markedly (overall p < 0.001): in the pancreatitis group EST was performed more often at the procedure (36.9% vs 22.3%) and “no EST” was more frequent (35.4% vs 21.3%), whereas having a previous EST was more common in those without pancreatitis (27.7% vs 56.4%). Post-hoc pairwise analysis demonstrated significant differences in the distribution of history of EST between groups a and b (p = 0.0027) and between b and c (p = 0.0030), whereas no significant difference was observed between groups a and c. Precut was used substantially more in patients who developed pancreatitis (40.9% vs 15.1%, p < 0.001). Distributions of immunosuppressive regimens were comparable (p = 0.504). Antibiotic use was much higher among pancreatitis cases (57.6% vs 12.5%, p < 0.001). Stent presence did not differ (78.8% vs 70.7%, p = 0.198). The pancreatitis group underwent more ERCP sessions (median 4.0 [IQR 2.0–7.0] vs 3.0 [2.0–5.0], p = 0.026) (Table 3 ). Table 3 Comparison of Characteristics by Pancreatitis Status Variable Pancreatitis (+) (n = 66) Pancreatitis (−) (n = 208) p value Age, years (mean ± SD) 48.32 ± 15.78 49.15 ± 13.57 0.676 Gender, n (%) 0.582 Female 24 (36.4) 68 (32.7) Male 42 (63.6) 140 (67.3) Graft lobe, n (%) 0.684 Right 65 (98.5) 201 (96.6) Left 1 (1.5) 7 (3.4) Anastomosis type, n (%) 0.184 Stricture 55 (83.3) 157 (75.5) Normal 11 (16.7) 51 (24.5) EST, n (%) < 0.001 Performed (a) 24 (36.9) 45 (22.3) Post-Hoc: a-b: 0.0027, b-c: p = 0.0030 History of EST (b) 18 (27.7) 114 (56.4) Not performed (c) 23 (35.4) 43 (21.3) Precut sphincterotomy, n (%) < 0.001 Yes 27 (40.9) 31 (15.1) No 39 (59.1) 174 (84.9) Immunosuppressive therapy, n (%) 0.504 Tacrolimus 31 (47.0) 98 (47.1) Everolimus 3 (4.5) 16 (7.7) Tacrolimus + everolimus 11 (16.7) 44 (21.2) Mycophenolate mofetil 3 (4.5) 13 (6.3) Prednisolone + others 18 (27.3) 37 (17.8) Antibiotic use, n (%) < 0.001 Yes 38 (57.6) 26 (12.5) No 28 (42.4) 182 (87.5) Biliary stent, n (%) 0.198 Present 52 (78.8) 147 (70.7) Absent 14 (21.2) 61 (29.3) ERCP sessions, median (IQR) 4.0 (2.0–7.0) 3.0 (2.0–5.0) 0.026 ERCP : Endoscopic Retrograde Cholangiopancreatography, EST : Endoscopic Sphincterotomy, IQR : Interquartile Range, SD : Standard Deviation In logistic regression, precut was strongly associated with post-ERCP pancreatitis: univariate OR 3.89 (95% CI 2.09–7.24; p < 0.001), remaining significant in multivariable analysis with OR 2.72 (1.37–5.42; p = 0.004). In contrast, having a previous EST was protective: univariate OR 0.30 (0.16–0.54; p < 0.001) and multivariable OR 0.43 (0.22–0.84; p = 0.013). Immunosuppressive regimen showed no significant association compared with tacrolimus (everolimus OR 0.59, p = 0.430; tacrolimus+everolimus OR 0.79, p = 0.551; mycophenolate mofetil OR 0.73, p = 0.639; prednisolone+others OR 1.54, p = 0.224). Thus, precut independently increased, while prior EST independently decreased, the odds of post-ERCP pancreatitis (Table 4 ). Table 4 Predictors of Post‑ERCP Pancreatitis: Univariate and Multivariate Logistic Regression Variable / Category Univariate OR (95% CI) p value Multivariate OR (95% CI) p value Age, years 1.005 (0.998–1.009) 0.115 Precut Not done (ref) 1 1 Done 3.886 (2.086–7.237) < 0.001 2.724 (1.368–5.422) 0.004 Previous EST Not performed (ref) 1 1 Performed 0.296 (0.161–0.544) < 0.001 0.426 (0.218–0.835) 0.013 Immunosuppressive therapy (ref = Tacrolimus) Everolimus 0.593 (0.162–2.170) 0.430 Tacrolimus + Everolimus 0.790 (0.364–1.714) 0.551 Mycophenolate mofetil 0.730 (0.195–2.728) 0.639 Prednisolone + others 1.538 (0.796–3.076) 0.224 OR : Odds Ratio, CI : Confidence Interval, EST : Endoscopic Sphincterotomy, Precut : Precut Sphincterotomy, MMF : Mycophenolate Mofetil, ref : Reference category Among patients who received antibiotics (n = 62) versus no antibiotics (n = 205), session characteristics differed significantly. Antibiotic recipients were more likely to have EST performed at the index ERCP (41.9% vs 21.0%) and to undergo a precut (34.4% vs 17.4%), while they were less likely to have had a prior EST (35.5% vs 53.7%) (all p = 0.003–0.004). In addition, stent presence was more frequent among those who received antibiotics (present vs absent: p = 0.037). Overall, antibiotic use clustered with procedures reflecting more complex or difficult cannulation (index EST, precut, and stenting) (Table 5 ). Table 5 Antibiotic Use and Procedural Features Among ERCP Patients Variable Antibiotics received (n = 62*) No antibiotics (n = 205*) p value Previous EST, n (%) 0.003 Performed during index ERCP 26 (41.9) 43 (21.0) History of prior EST 22 (35.5) 110 (53.7) No EST 14 (22.6) 52 (25.4) Precut sphincterotomy, n (%) 0.004 Yes 22 (34.4) 36 (17.4) No 42 (65.6) 171 (82.6) Biliary stent, n (%) 0.037 Present 53 (85.3) 146 (71.2) Absent 11 (14.7) 59 (28.8) ERCP : Endoscopic Retrograde Cholangiopancreatography, EST : Endoscopic Sphincterotomy DISCUSSION Biliary tract complications occur in approximately 5–30% of patients after liver transplantation. These complications can be managed with therapeutic ERCP, percutaneous transhepatic biliary drainage (PTBD), or surgery. In contemporary practice, ERCP has largely replaced surgery as the first-line (gold-standard) procedure for the diagnosis and treatment of biliary complications in liver-transplant recipients. However, the incidence and risk factors for post-ERCP complications in this population are not uniformly defined, and reported rates vary across studies ( 12 – 15 ). The variability across studies likely reflects differences in procedural settings (e.g., high-volume expert centers vs. smaller units) and patient-related factors (recipient, graft, and anastomotic characteristics). To clarify risk profiles and standardize care, larger, well-designed retrospective and prospective studies are needed. In our cohort of living-donor liver transplant recipients, the incidence of post-ERCP pancreatitis was 4.9%, which is broadly consistent with published ranges in transplant populations. In our study, we compared the development of PEP between sexes and found no statistically significant difference. The notion—now incorporated into the latest ESGE guideline—that female sex confers a higher risk of PEP is largely derived from the meta-analysis by Masci et al. ( 16 ), which pooled seven studies including 7,524 female patients and reported that the incidence of PEP in women was nearly twofold that observed in men. In a retrospective analysis of 758 cases, Finkelmeier et al. ( 17 ) reported that the risk of PEP decreases with age, with a markedly lower risk observed in patients aged ≥ 80 years. In contrast, Freeman et al. ( 18 ) found no association between age and PEP. Consistent with the findings of Freeman et al., our study also demonstrated no relationship between age and PEP (p = 0.676). Accordingly, because age did not reach statistical significance in univariate analysis, it was not included in the multivariate logistic regression model, an approach that is in line with several previous studies. The divergent results across studies may be attributable to differences in sample size, case mix, referral patterns, and procedural practices. Many clinical studies have shown that precut sphincterotomy increases the risk of PEP ( 18 ). The proposed mechanisms include thermal injury–related edema of periampullary tissues that can obstruct the pancreatic duct (Wirsung) and the fact that precut is often performed after prolonged, difficult cannulation, both of which may elevate PEP risk. In a meta-analysis of 15 prospective trials, Masci et al. ( 16 ) reported that precut sphincterotomy increased the risk of PEP by 2.71-fold (95% CI, 2.02–3.63; p < 0.001). Consistent with these data, in our cohort precut during ERCP was associated with a markedly higher odds of PEP—OR 3.88 (95% CI, 2.086–7.237; p < 0.001) in univariate analysis and adjusted OR 2.724 (95% CI, 1.368–5.422; p = 0.004) in multivariable analysis. In our cohort, prior EST was associated with a markedly lower likelihood of post-ERCP pancreatitis (unadjusted OR 0.296; 70.4% reduction; p < 0.001), an effect that persisted after adjustment (adjusted OR 0.426; p = 0.013). This finding is biologically plausible: EST—first described by Classen and Kawai in 1974—reduces sphincter resistance, and pancreatic-duct irritation from the cut may transiently obstruct the duct via periductal edema (Akashi et al.), potentially modifying pancreatitis risk ( 19 ). In this study, placement of a stent during ERCP did not affect the rate of pancreatitis (p = 0.198). However, patients who had a stent placed during the procedure had a higher incidence of post-ERCP antibiotic treatment (p = 0.037). Likewise, post-procedural antibiotic use was analyzed in patients who underwent a precut during ERCP (p = 0.04) and in those with a previous EST (p = 0.03), and in both groups antibiotic use was found to be significantly higher. Drug-induced pancreatitis is uncommon (≈ 0.1–2%) and difficult to quantify because evidence is dominated by case reports and small series; nevertheless, hundreds of agents—including transplant immunosuppressants—have been implicated. Prior classifications have placed prednisolone in a higher-probability tier and tacrolimus in a lower tier, and isolated reports describe tacrolimus-associated pancreatitis and acinar injury, while a recent retrospective LDLT cohort suggested higher tacrolimus levels (> 2.5 ng/mL) might be associated with lower PEP odds—though most patients there also received rectal indomethacin ( 20 – 23 ). In our study of liver-transplant recipients, no immunosuppressive agent showed a significant association with PEP when compared with tacrolimus as the reference: everolimus OR 0.593 (95% CI 0.162–2.170; p = 0.430), tacrolimus+everolimus OR 0.790 (0.364–1.714; p = 0.551), mycophenolate mofetil OR 0.730 (0.195–2.728; p = 0.639), and prednisolone ± others OR 1.538 (0.796–3.076; p = 0.224). Taken together, the literature is mixed and largely non-definitive, and our data do not support a protective or harmful effect of routine immunosuppressive regimens on PEP risk. The principal limitation of this study is its retrospective design, which carries risks of incomplete documentation, missing data, and unmeasured confounding, and therefore precludes causal inference. In addition, being a single-center study may reflect local case-mix, operator experience, and institutional protocols, which limits external validity and generalizability to other settings. CONCLUSION Among living-donor liver transplant recipients, PEP occurred in 66 (5.6%) patients. Precut sphincterotomy independently increased PEP, whereas prior EST was protective. Stent placement did not affect PEP, though stenting—as with precut and prior EST—coincided with greater post-procedure antibiotic use, likely reflecting case complexity. Immunosuppressants (tacrolimus, everolimus, mycophenolate, prednisolone ± others) showed no association with PEP. These data support careful cannulation, judicious precut, and standard PEP prophylaxis in higher-risk cases. Declarations Ethics approval and consent to participate: The study was conducted retrospectively after approval by the İnönü University Ethics Committee (Data: 29/09/2020, decision no. 2020/1060) and a written informed consent was obtained from each participant before enrolled to the study. Consent for publication: Not applicable Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests : None. Funding : No funding interests. Authors' contributions : All authors took responsibility and took part in the design (S.A.), data collection (G.Y.), statistical analysis (J.K.), writing (Y.B.), and critical review (S.Ç.) of the study. Acknowledgements : Nothing to declare. Clinical Trial Number : Not applicable References Akamatsu N, Sugawara Y, Hashimoto D. Biliary reconstruction, its complications and management in living-donor liver transplantation. 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Gastrointest Endosc. 2009;70:80–8. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Vege SS. Classification of acute pancreatitis—2012: Revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102–11. https://doi.org/10.1136/gutjnl-2012-302779 . Alomari M, Richards A, Fernando D, O’Neill J. Post-ERCP complications in liver transplant recipients: A systematic review and meta-analysis. Gastroenterol Res. 2021;14(6):341–52. https://doi.org/10.14740/gr1391 . American Society for Gastrointestinal Endoscopy. (2023). Guideline on management of post–liver transplant biliary strictures: Methodology and review of evidence. Retrieved from https://www.asge.org Balderramo D, Navasa M, Cardenas A, Koo M, Alvarado-Tapias E, Darnell A, García-Pagán JC, Rimola A. Complications after ERCP in liver transplant recipients. Gastroenterology. 2011;141(4):1206–13. https://doi.org/10.1053/j.gastro.2011.06.072 . Boeva I, Serkova N. 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Acute pancreatitis due to tacrolimus in kidney transplant: Case report and literature review. J Clin Pharm Ther. (Advance online publication). Jin S, Orabi AI, Le T, Javed TA, Sah S, Eisses JF, et al. Exposure to radiocontrast agents induces pancreatic inflammation by activation of nuclear factor-κB, calcium signaling, and calcineurin. Gastroenterology. 2015;149:753–64. Thiruvengadam NR, Forde KA, Chandrasekhara V, Ahmad NA, Ginsberg GG, Khungar V. Tacrolimus and indomethacin are safe and effective at reducing pancreatitis after ERCP in liver-transplant recipients. Clin Gastroenterol Hepatol. 2020;18:1224–32. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 22 Feb, 2026 Reviewers agreed at journal 21 Feb, 2026 Reviewers invited by journal 18 Feb, 2026 Editor invited by journal 27 Jan, 2026 Editor assigned by journal 26 Jan, 2026 Submission checks completed at journal 26 Jan, 2026 First submitted to journal 21 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8661362","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":595168396,"identity":"875e1a85-c856-4086-b06d-5b0917559f84","order_by":0,"name":"Gülşah YAMANCAN","email":"","orcid":"","institution":"Fırat University","correspondingAuthor":false,"prefix":"","firstName":"Gülşah","middleName":"","lastName":"YAMANCAN","suffix":""},{"id":595168399,"identity":"e876afef-be43-49ca-9935-f06ad23d786e","order_by":1,"name":"Jehat Kılıç","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYBACxgYeEJXAw8fMwPgAyJJhYGAjQssBoBY2ZgZmAwYGAx6CWhgYIFpA6tgkiNLC3N578PMHhjQZNnbmZxUf2/7w8LO3JTD8qNiG22E955IlDjDkAB3GZnZzZpsBj2TPsQOMPWdu49YyI8cAqKUCqIWH7TYvUIvBjfQGZsY2PFrmvzH+AdNSTJyWGTxmUIcBEURL2gH8WnpyzCzOMKSB/GIsOeOcMcgvCQfx+cWw/YzxjQqGZHt+/sMPP3wok5MDhpjhgx8VeLQ0gKz6hyZ6AKd6IJDHJzkKRsEoGAWjAAwASOxJ8vI78sIAAAAASUVORK5CYII=","orcid":"","institution":"Fırat University","correspondingAuthor":true,"prefix":"","firstName":"Jehat","middleName":"","lastName":"Kılıç","suffix":""},{"id":595168401,"identity":"62f8ad81-07fb-4411-baa7-677db401d41c","order_by":2,"name":"Sedat Çiçek","email":"","orcid":"","institution":"Fırat University","correspondingAuthor":false,"prefix":"","firstName":"Sedat","middleName":"","lastName":"Çiçek","suffix":""},{"id":595168405,"identity":"95831ed6-f490-471f-bbfc-4a12c9eac60e","order_by":3,"name":"Sami Akbulut","email":"","orcid":"","institution":"Inonu University","correspondingAuthor":false,"prefix":"","firstName":"Sami","middleName":"","lastName":"Akbulut","suffix":""},{"id":595168408,"identity":"a1aad23e-d2df-405b-bd1a-6ef5d6da7dd9","order_by":4,"name":"Yılmaz Bilgiç","email":"","orcid":"","institution":"Istanbul Medipol University","correspondingAuthor":false,"prefix":"","firstName":"Yılmaz","middleName":"","lastName":"Bilgiç","suffix":""}],"badges":[],"createdAt":"2026-01-21 15:08:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8661362/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8661362/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103216362,"identity":"3fecb773-b700-4dee-9865-e7e14027528c","added_by":"auto","created_at":"2026-02-23 09:33:27","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":427746,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of patient selection and study cohort\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8661362/v1/a3f50ea47b8a99d88cb80636.png"},{"id":103504995,"identity":"88eb458d-aec8-45de-b461-94e6ae632f76","added_by":"auto","created_at":"2026-02-26 13:22:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1331213,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8661362/v1/8b9cce3a-0485-449a-bead-77db7226c017.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Effect of Immunsuppressive Treatment Agents on Post-ERCP Pancreatitis in Living Donor Liver Transplant Patients","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eLiver transplantation is now a widely used and effective therapy for end-stage liver disease, with modern surgery and immunosuppression improving outcomes substantially (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Biliary complications, however, remain common (\u0026asymp;\u0026thinsp;10\u0026ndash;30%) and are seen more frequently after living-donor transplants where multiple ductal anastomoses are required (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Well-described risk factors for anastomotic or non-anastomotic strictures include technical issues, prolonged cold/warm ischemia, older donor age, and hepatic artery thrombosis/ischemia (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). For most biliary complications, endoscopic therapy\u0026mdash;principally ERCP with sphincterotomy, dilation, and stenting\u0026mdash;has largely supplanted surgery as first-line management (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eERCP is the cornerstone of managing benign biliary strictures after liver transplantation. PEP is the most frequent ERCP-related adverse event, occurring in roughly 2\u0026ndash;10% of unselected cases and up to ~\u0026thinsp;20\u0026ndash;24% in high-risk settings (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Most episodes are mild, but a minority progress to moderately severe or severe disease and can be fatal; overall mortality is low but higher in severe cases (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Randomized and guideline evidence support effective prophylaxis\u0026mdash;particularly rectal NSAIDs for nearly all patients and pancreatic-duct stenting in selected high-risk cannulations (\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePEP is multifactorial. The initiating event is thought to be early acinar-cell injury with premature intrapancreatic trypsin activation, which triggers a sterile inflammatory cascade. Procedure-related contributors include mechanical trauma to the papilla/pancreatic duct from repeated or difficult cannulation and guidewire passage; hydrostatic over-distension from contrast injection; thermal/diathermic injury during (pre-cut) sphincterotomy; and transient papillary edema or spasm causing outflow obstruction. These insults are amplified in susceptible hosts (e.g., prior PEP, suspected sphincter of Oddi dysfunction, female sex), and can be modulated by local microbial contamination and patient biology. Together, these factors raise ductal pressure, promote zymogen activation, and propagate local and systemic inflammation. [7,10]\u003c/p\u003e \u003cp\u003eBecause PEP is the most frequent major adverse event after ERCP and is not uncommon in liver-transplant recipients, our primary objectives were to estimate the incidence of PEP in this population, identify procedure- and patient-related risk factors, and examine, in particular, the association between specific immunosuppressive agents and PEP.\u003c/p\u003e"},{"header":"MATERIAL METHODS","content":"\u003cp\u003eThis single-center, retrospective clinical study included 1,338 liver-transplant recipients who underwent ERCP at the Department of Gastroenterology, İn\u0026ouml;n\u0026uuml; University School of Medicine, between January 2012 and February 2020. Patient data were extracted from the Turgut \u0026Ouml;zal Medical Center archives. The study was conducted retrospectively after approval by the İn\u0026ouml;n\u0026uuml; University Ethics Committee (Data: 29/09/2020, decision no. 2020/1060).\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStudy description and patient selection\u003c/strong\u003e \u003cp\u003eAll liver transplant recipients who underwent ERCP at our center between January 2012 and February 2020 were initially reviewed (n\u0026thinsp;=\u0026thinsp;1,338). Patients were excluded if ERCP or follow-up information was incomplete, if essential clinical or laboratory data required to assess PEP were missing, or if the procedure was non-biliary or technically unsuccessful. After these exclusions, 274 patients with complete and reliable datasets remained and constituted the final study cohort. In this group, a total of 1,174 ERCP sessions were analyzed.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eFor each included patient, relevant demographic, clinical, procedural, and treatment-related information was retrospectively collected from electronic medical records. Extracted variables included age and sex; the indication for liver transplantation; the type of biliary anastomosis performed at transplantation (duct-to-duct or Roux-en-Y hepaticojejunostomy); history of prior endoscopic sphincterotomy (EST); use of pre-cut (needle-knife) sphincterotomy during ERCP; placement of a common bile duct stent; the maintenance immunosuppressive regimen at the time of ERCP; administration of post-procedure antibiotics; the indication for ERCP; and the total number of ERCP sessions per patient. The occurrence of PEP was assessed at the patient level and served as the primary outcome of the study (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eDefinition of PEP\u003c/b\u003e: PEP was diagnosed according to the revised Atlanta criteria, requiring\u0026thinsp;\u0026ge;\u0026thinsp;2 of the following: (i) new or worsening epigastric pain consistent with acute pancreatitis and necessitating analgesia; (ii) serum amylase and/or lipase\u0026thinsp;\u0026gt;\u0026thinsp;3\u0026times; the upper limit of normal at ~\u0026thinsp;24 hours after ERCP; (iii) imaging findings on contrast-enhanced abdominal CT compatible with acute pancreatitis (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eImmunosuppression regimen (center protocol)\u003c/strong\u003e \u003cp\u003eDuring the study period, the standard post-transplant regimen at İn\u0026ouml;n\u0026uuml; University Turgut \u0026Ouml;zal Medical Center Liver Transplant Institute consisted of tacrolimus, everolimus, mycophenolate mofetil (MMF), and prednisolone. An initial dose of methylprednisolone (500 mg or 20 mg/kg) was administered immediately after completion of the hepatic artery anastomosis and tapered postoperatively from 100 mg/day to 5 mg/day; steroids were discontinued at month 3 except in autoimmune liver diseases (autoimmune hepatitis, primary sclerosing cholangitis, or primary biliary cholangitis). Tacrolimus (0.02\u0026ndash;0.05 mg/kg/day) and MMF (10\u0026ndash;30 mg/kg/day) were initiated on postoperative day 3, with tacrolimus trough targets of 7\u0026ndash;10 ng/mL in the first year and 3\u0026ndash;5 ng/mL thereafter. In patients who developed renal dysfunction (or calcineurin-inhibitor neurotoxicity), tacrolimus was withheld and switched to everolimus until renal function improved, or the tacrolimus dose was reduced and low-dose everolimus was added.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical grouping of immunosuppressants.\u003c/b\u003e For risk modeling, immunosuppressive exposure was categorized with priority to tacrolimus and everolimus. Patients not receiving either agent for any reason were grouped as MMF or Other (steroids, sirolimus, or cyclosporine).\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStatistical Analysis\u003c/strong\u003e \u003cp\u003eNormality of continuous variables was assessed with the Shapiro\u0026ndash;Wilk test and homogeneity of variances with Levene\u0026rsquo;s test. For two-group comparisons, the independent-samples \u003cem\u003et\u003c/em\u003e test was used when normality was satisfied; otherwise, the Mann\u0026ndash;Whitney U test was applied. Categorical variables were compared with the χ\u0026sup2; test. To evaluate the diagnostic performance of \u0026ldquo;number of ERCP sessions\u0026rdquo; for predicting post-ERCP pancreatitis, receiver operating characteristic (ROC) analysis was performed and ROC curves were plotted. Cut-off values were determined using the Youden index, and sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Risk factors associated with pancreatitis were examined using univariable and multivariable logistic regression (enter method). Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e \u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eAmong 274 patients, 92 (33.6%) were female and 182 (66.4%) male. Most procedures involved the right lobe (266, 97.1%) rather than the left (8, 2.9%). The anastomosis was most commonly a stricture (212, 77.4%), with fewer normal (56, 20.4%) or other types (6, 2.2%). Regarding EST, 132 (49.4%) had a previous EST, 69 (25.8%) had EST performed (recorded in history), and 66 (24.7%) had no EST. A precut was done in 58 (21.4%) and not done in 213 (78.6%). Immunosuppressive regimens included tacrolimus in 129 (47.1%), everolimus in 19 (6.9%), tacrolimus\u0026thinsp;+\u0026thinsp;everolimus in 55 (20.1%), mycophenolate mofetil in 16 (5.8%), and prednisolone\u0026thinsp;\u0026plusmn;\u0026thinsp;others in 55 (20.1%). Antibiotics were given to 64 (23.4%) while 210 (76.6%) did not receive them. Stents were present in 199 (72.6%) and absent in 75 (27.4%). Pancreatitis occurred in 66 (24.1%) overall and was not observed in 208 (75.9%). Among those evaluated after the first session (n\u0026thinsp;=\u0026thinsp;66), post-session pancreatitis was observed in 38 (57.5%) and not observed in 28 (42.5%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Characteristics and Procedural Details of the Study Cohort\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCount (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e33.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e182\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e66.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLobe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e97.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of anastomosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStricture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e77.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePerformed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHad previous EST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e49.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrecut\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot done\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e78.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppressive therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTacrolimus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e129\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e47.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEverolimus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTacrolimus\u0026thinsp;+\u0026thinsp;Everolimus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMycophenolate mofetil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrednisolone\u0026thinsp;+\u0026thinsp;others\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotic use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReceived antibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDid not receive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e76.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e199\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e72.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e27.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePancreatitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eObserved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot observed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e75.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost\u0026ndash;first session pancreatitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot observed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eObserved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eEST\u003c/b\u003e: Endoscopic Sphincterotomy, \u003cb\u003ePrecut\u003c/b\u003e: Precut Sphincterotomy, \u003cb\u003eMMF\u003c/b\u003e: Mycophenolate Mofetil, \u003cb\u003eERCP\u003c/b\u003e: Endoscopic Retrograde Cholangiopancreatography\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong 266 ERCPs, the most common indication was anastomotic stricture in 200 cases (75.2%). Less frequent indications included bile leak in 21 (7.9%), non-anastomotic stricture in 16 (6.0%), anastomotic stricture with stone in 11 (4.1%), and anastomotic stricture with leak in 10 (3.8%). Normal ERCP findings accounted for 7 procedures (2.6%), and feeding catheter in the common bile duct was the indication in 1 case (0.4%). Overall totals sum to 266 procedures (100%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIndications for ERCP\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCount (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnastomotic stricture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e75.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBile leak\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon‑anastomotic stricture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnastomotic stricture\u0026thinsp;+\u0026thinsp;stone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnastomotic stricture\u0026thinsp;+\u0026thinsp;leak\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal ERCP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeeding catheter in the common bile duct\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cb\u003eERCP\u003c/b\u003e: Endoscopic Retrograde Cholangiopancreatography\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn 274 ERCPs, pancreatitis developed in 66 patients (24.1%). Age and sex did not differ between groups (48.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8 vs 49.2\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6 years; female 36.4% vs 32.7%; both p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Lobe side and anastomosis type were also similar (right lobe 98.5% vs 96.6%; stricture 83.3% vs 75.5%; both p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Prior/ongoing EST status differed markedly (overall p\u0026thinsp;\u0026lt;\u0026thinsp;0.001): in the pancreatitis group EST was performed more often at the procedure (36.9% vs 22.3%) and \u0026ldquo;no EST\u0026rdquo; was more frequent (35.4% vs 21.3%), whereas having a previous EST was more common in those without pancreatitis (27.7% vs 56.4%). Post-hoc pairwise analysis demonstrated significant differences in the distribution of history of EST between groups a and b (p\u0026thinsp;=\u0026thinsp;0.0027) and between b and c (p\u0026thinsp;=\u0026thinsp;0.0030), whereas no significant difference was observed between groups a and c. Precut was used substantially more in patients who developed pancreatitis (40.9% vs 15.1%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Distributions of immunosuppressive regimens were comparable (p\u0026thinsp;=\u0026thinsp;0.504). Antibiotic use was much higher among pancreatitis cases (57.6% vs 12.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Stent presence did not differ (78.8% vs 70.7%, p\u0026thinsp;=\u0026thinsp;0.198). The pancreatitis group underwent more ERCP sessions (median 4.0 [IQR 2.0\u0026ndash;7.0] vs 3.0 [2.0\u0026ndash;5.0], p\u0026thinsp;=\u0026thinsp;0.026) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Characteristics by Pancreatitis Status\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePancreatitis (+) (n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePancreatitis (\u0026minus;) (n\u0026thinsp;=\u0026thinsp;208)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.32\u0026thinsp;\u0026plusmn;\u0026thinsp;15.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.15\u0026thinsp;\u0026plusmn;\u0026thinsp;13.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.676\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.582\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (32.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e140 (67.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGraft lobe, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.684\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (98.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e201 (96.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnastomosis type, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.184\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStricture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (83.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e157 (75.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEST, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerformed (a)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (36.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (22.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePost-Hoc: a-b: 0.0027, b-c: p\u0026thinsp;=\u0026thinsp;0.0030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of EST (b)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (27.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e114 (56.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot performed (c)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (21.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrecut sphincterotomy, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (40.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (15.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (59.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e174 (84.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eImmunosuppressive therapy, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.504\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTacrolimus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (47.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98 (47.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEverolimus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTacrolimus\u0026thinsp;+\u0026thinsp;everolimus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (21.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycophenolate mofetil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrednisolone\u0026thinsp;+\u0026thinsp;others\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntibiotic use, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e182 (87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBiliary stent, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.198\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (78.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e147 (70.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (21.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (29.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eERCP sessions, median (IQR)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.0 (2.0\u0026ndash;7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0 (2.0\u0026ndash;5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eERCP\u003c/b\u003e: Endoscopic Retrograde Cholangiopancreatography, \u003cb\u003eEST\u003c/b\u003e: Endoscopic Sphincterotomy, \u003cb\u003eIQR\u003c/b\u003e: Interquartile Range, \u003cb\u003eSD\u003c/b\u003e: Standard Deviation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn logistic regression, precut was strongly associated with post-ERCP pancreatitis: univariate OR 3.89 (95% CI 2.09\u0026ndash;7.24; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), remaining significant in multivariable analysis with OR 2.72 (1.37\u0026ndash;5.42; p\u0026thinsp;=\u0026thinsp;0.004). In contrast, having a previous EST was protective: univariate OR 0.30 (0.16\u0026ndash;0.54; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and multivariable OR 0.43 (0.22\u0026ndash;0.84; p\u0026thinsp;=\u0026thinsp;0.013). Immunosuppressive regimen showed no significant association compared with tacrolimus (everolimus OR 0.59, p\u0026thinsp;=\u0026thinsp;0.430; tacrolimus+everolimus OR 0.79, p\u0026thinsp;=\u0026thinsp;0.551; mycophenolate mofetil OR 0.73, p\u0026thinsp;=\u0026thinsp;0.639; prednisolone+others OR 1.54, p\u0026thinsp;=\u0026thinsp;0.224). Thus, precut independently increased, while prior EST independently decreased, the odds of post-ERCP pancreatitis (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePredictors of Post‑ERCP Pancreatitis: Univariate and Multivariate Logistic Regression\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable / Category\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnivariate OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMultivariate OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.005 (0.998\u0026ndash;1.009)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrecut\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot done (ref)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.886 (2.086\u0026ndash;7.237)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.724 (1.368\u0026ndash;5.422)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious EST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot performed (ref)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerformed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.296 (0.161\u0026ndash;0.544)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.426 (0.218\u0026ndash;0.835)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppressive therapy (ref\u0026thinsp;=\u0026thinsp;Tacrolimus)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEverolimus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.593 (0.162\u0026ndash;2.170)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.430\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTacrolimus\u0026thinsp;+\u0026thinsp;Everolimus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.790 (0.364\u0026ndash;1.714)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.551\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycophenolate mofetil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.730 (0.195\u0026ndash;2.728)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.639\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrednisolone\u0026thinsp;+\u0026thinsp;others\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.538 (0.796\u0026ndash;3.076)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.224\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003eOR\u003c/b\u003e: Odds Ratio, \u003cb\u003eCI\u003c/b\u003e: Confidence Interval, \u003cb\u003eEST\u003c/b\u003e: Endoscopic Sphincterotomy, \u003cb\u003ePrecut\u003c/b\u003e: Precut Sphincterotomy, \u003cb\u003eMMF\u003c/b\u003e: Mycophenolate Mofetil, \u003cb\u003eref\u003c/b\u003e: Reference category\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong patients who received antibiotics (n\u0026thinsp;=\u0026thinsp;62) versus no antibiotics (n\u0026thinsp;=\u0026thinsp;205), session characteristics differed significantly. Antibiotic recipients were more likely to have EST performed at the index ERCP (41.9% vs 21.0%) and to undergo a precut (34.4% vs 17.4%), while they were less likely to have had a prior EST (35.5% vs 53.7%) (all p\u0026thinsp;=\u0026thinsp;0.003\u0026ndash;0.004). In addition, stent presence was more frequent among those who received antibiotics (present vs absent: p\u0026thinsp;=\u0026thinsp;0.037). Overall, antibiotic use clustered with procedures reflecting more complex or difficult cannulation (index EST, precut, and stenting) (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntibiotic Use and Procedural Features Among ERCP Patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAntibiotics received (n\u0026thinsp;=\u0026thinsp;62*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo antibiotics (n\u0026thinsp;=\u0026thinsp;205*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrevious EST, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerformed during index ERCP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26 (41.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43 (21.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of prior EST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (35.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e110 (53.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo EST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52 (25.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrecut sphincterotomy, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (34.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36 (17.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42 (65.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e171 (82.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBiliary stent, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.037\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e53 (85.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e146 (71.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (14.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e59 (28.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eERCP\u003c/b\u003e: Endoscopic Retrograde Cholangiopancreatography, \u003cb\u003eEST\u003c/b\u003e: Endoscopic Sphincterotomy\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eBiliary tract complications occur in approximately 5\u0026ndash;30% of patients after liver transplantation. These complications can be managed with therapeutic ERCP, percutaneous transhepatic biliary drainage (PTBD), or surgery. In contemporary practice, ERCP has largely replaced surgery as the first-line (gold-standard) procedure for the diagnosis and treatment of biliary complications in liver-transplant recipients. However, the incidence and risk factors for post-ERCP complications in this population are not uniformly defined, and reported rates vary across studies (\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The variability across studies likely reflects differences in procedural settings (e.g., high-volume expert centers vs. smaller units) and patient-related factors (recipient, graft, and anastomotic characteristics). To clarify risk profiles and standardize care, larger, well-designed retrospective and prospective studies are needed. In our cohort of living-donor liver transplant recipients, the incidence of post-ERCP pancreatitis was 4.9%, which is broadly consistent with published ranges in transplant populations.\u003c/p\u003e \u003cp\u003eIn our study, we compared the development of PEP between sexes and found no statistically significant difference. The notion\u0026mdash;now incorporated into the latest ESGE guideline\u0026mdash;that female sex confers a higher risk of PEP is largely derived from the meta-analysis by Masci et al. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), which pooled seven studies including 7,524 female patients and reported that the incidence of PEP in women was nearly twofold that observed in men.\u003c/p\u003e \u003cp\u003eIn a retrospective analysis of 758 cases, Finkelmeier et al. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) reported that the risk of PEP decreases with age, with a markedly lower risk observed in patients aged\u0026thinsp;\u0026ge;\u0026thinsp;80 years. In contrast, Freeman et al. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) found no association between age and PEP. Consistent with the findings of Freeman et al., our study also demonstrated no relationship between age and PEP (p\u0026thinsp;=\u0026thinsp;0.676). Accordingly, because age did not reach statistical significance in univariate analysis, it was not included in the multivariate logistic regression model, an approach that is in line with several previous studies. The divergent results across studies may be attributable to differences in sample size, case mix, referral patterns, and procedural practices.\u003c/p\u003e \u003cp\u003eMany clinical studies have shown that precut sphincterotomy increases the risk of PEP (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The proposed mechanisms include thermal injury\u0026ndash;related edema of periampullary tissues that can obstruct the pancreatic duct (Wirsung) and the fact that precut is often performed after prolonged, difficult cannulation, both of which may elevate PEP risk. In a meta-analysis of 15 prospective trials, Masci et al. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) reported that precut sphincterotomy increased the risk of PEP by 2.71-fold (95% CI, 2.02\u0026ndash;3.63; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Consistent with these data, in our cohort precut during ERCP was associated with a markedly higher odds of PEP\u0026mdash;OR 3.88 (95% CI, 2.086\u0026ndash;7.237; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in univariate analysis and adjusted OR 2.724 (95% CI, 1.368\u0026ndash;5.422; p\u0026thinsp;=\u0026thinsp;0.004) in multivariable analysis.\u003c/p\u003e \u003cp\u003eIn our cohort, prior EST was associated with a markedly lower likelihood of post-ERCP pancreatitis (unadjusted OR 0.296; 70.4% reduction; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), an effect that persisted after adjustment (adjusted OR 0.426; p\u0026thinsp;=\u0026thinsp;0.013). This finding is biologically plausible: EST\u0026mdash;first described by Classen and Kawai in 1974\u0026mdash;reduces sphincter resistance, and pancreatic-duct irritation from the cut may transiently obstruct the duct via periductal edema (Akashi et al.), potentially modifying pancreatitis risk (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this study, placement of a stent during ERCP did not affect the rate of pancreatitis (p\u0026thinsp;=\u0026thinsp;0.198). However, patients who had a stent placed during the procedure had a higher incidence of post-ERCP antibiotic treatment (p\u0026thinsp;=\u0026thinsp;0.037). Likewise, post-procedural antibiotic use was analyzed in patients who underwent a precut during ERCP (p\u0026thinsp;=\u0026thinsp;0.04) and in those with a previous EST (p\u0026thinsp;=\u0026thinsp;0.03), and in both groups antibiotic use was found to be significantly higher.\u003c/p\u003e \u003cp\u003eDrug-induced pancreatitis is uncommon (\u0026asymp;\u0026thinsp;0.1\u0026ndash;2%) and difficult to quantify because evidence is dominated by case reports and small series; nevertheless, hundreds of agents\u0026mdash;including transplant immunosuppressants\u0026mdash;have been implicated. Prior classifications have placed prednisolone in a higher-probability tier and tacrolimus in a lower tier, and isolated reports describe tacrolimus-associated pancreatitis and acinar injury, while a recent retrospective LDLT cohort suggested higher tacrolimus levels (\u0026gt;\u0026thinsp;2.5 ng/mL) might be associated with lower PEP odds\u0026mdash;though most patients there also received rectal indomethacin (\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In our study of liver-transplant recipients, no immunosuppressive agent showed a significant association with PEP when compared with tacrolimus as the reference: everolimus OR 0.593 (95% CI 0.162\u0026ndash;2.170; p\u0026thinsp;=\u0026thinsp;0.430), tacrolimus+everolimus OR 0.790 (0.364\u0026ndash;1.714; p\u0026thinsp;=\u0026thinsp;0.551), mycophenolate mofetil OR 0.730 (0.195\u0026ndash;2.728; p\u0026thinsp;=\u0026thinsp;0.639), and prednisolone\u0026thinsp;\u0026plusmn;\u0026thinsp;others OR 1.538 (0.796\u0026ndash;3.076; p\u0026thinsp;=\u0026thinsp;0.224). Taken together, the literature is mixed and largely non-definitive, and our data do not support a protective or harmful effect of routine immunosuppressive regimens on PEP risk.\u003c/p\u003e \u003cp\u003eThe principal limitation of this study is its retrospective design, which carries risks of incomplete documentation, missing data, and unmeasured confounding, and therefore precludes causal inference. In addition, being a single-center study may reflect local case-mix, operator experience, and institutional protocols, which limits external validity and generalizability to other settings.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eAmong living-donor liver transplant recipients, PEP occurred in 66 (5.6%) patients. Precut sphincterotomy independently increased PEP, whereas prior EST was protective. Stent placement did not affect PEP, though stenting\u0026mdash;as with precut and prior EST\u0026mdash;coincided with greater post-procedure antibiotic use, likely reflecting case complexity. Immunosuppressants (tacrolimus, everolimus, mycophenolate, prednisolone\u0026thinsp;\u0026plusmn;\u0026thinsp;others) showed no association with PEP. These data support careful cannulation, judicious precut, and standard PEP prophylaxis in higher-risk cases.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate:\u003c/em\u003e The study was conducted retrospectively after approval by the İn\u0026ouml;n\u0026uuml; University Ethics Committee (Data: 29/09/2020, decision no. 2020/1060) and a written informed consent was obtained from each participant before enrolled to the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication:\u003c/em\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials:\u003c/em\u003e The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e: None.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e: No funding interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026apos; contributions\u003c/em\u003e: All authors took responsibility and took part in the design (S.A.), data collection (G.Y.), statistical analysis (J.K.), writing (Y.B.), and critical review (S.\u0026Ccedil;.) of the study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e: Nothing to declare.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eClinical Trial Number\u003c/em\u003e: Not applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAkamatsu N, Sugawara Y, Hashimoto D. 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Guideline on management of post\u0026ndash;liver transplant biliary strictures: Methodology and review of evidence. Retrieved from \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.asge.org\u003c/span\u003e\u003cspan address=\"https://www.asge.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBalderramo D, Navasa M, Cardenas A, Koo M, Alvarado-Tapias E, Darnell A, Garc\u0026iacute;a-Pag\u0026aacute;n JC, Rimola A. Complications after ERCP in liver transplant recipients. 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Endoscopy. 2003;35:830\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOld O, Hardy T, Hewin D, Barr H, Brown J. Risk of post-ERCP pancreatitis declines with age. Gastrointest Endosc. 2016;83:1307\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFreeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996;335:909\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkashi R, Kiyozumi T, Tanaka T, Sakurai K, Oda Y, Sagara K. Mechanism of pancreatitis caused by ERCP. Gastrointest Endosc. 2002;55:50\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBadalov N, Baradarian R, Iswara K, Li J, Steinberg W, Tenner S. Drug-induced acute pancreatitis: An evidence-based review. Clin Gastroenterol Hepatol. 2007;5:648\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu X-H, Chen H, Tan R-Y, Luo C. (2020). Acute pancreatitis due to tacrolimus in kidney transplant: Case report and literature review. J Clin Pharm Ther. (Advance online publication).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJin S, Orabi AI, Le T, Javed TA, Sah S, Eisses JF, et al. Exposure to radiocontrast agents induces pancreatic inflammation by activation of nuclear factor-κB, calcium signaling, and calcineurin. Gastroenterology. 2015;149:753\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThiruvengadam NR, Forde KA, Chandrasekhara V, Ahmad NA, Ginsberg GG, Khungar V. Tacrolimus and indomethacin are safe and effective at reducing pancreatitis after ERCP in liver-transplant recipients. Clin Gastroenterol Hepatol. 2020;18:1224\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Liver Transplantation, Endoscopic Retrograde Cholangiopancreatography, Post-ERCP Pancreatitis, Immunosuppression","lastPublishedDoi":"10.21203/rs.3.rs-8661362/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8661362/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eLiver transplantation is now routine for end-stage liver disease, but biliary complications occur in ~\u0026thinsp;5\u0026ndash;30% of recipients. Endoscopic retrograde cholangio-pancreatography (ERCP) has become the gold standard for managing these issues, yet post-ERCP pancreatitis (PEP) remains the most common adverse event, and its risk factors in transplant patients are not well defined. We aimed to identify predictors of PEP in liver transplant recipients, with a specific focus on the association between immunosuppressive therapy and PEP.\u003c/p\u003e\u003ch2\u003eMaterials and Methods.\u003c/h2\u003e \u003cp\u003eThis single-center retrospective cohort included 1,338 liver-transplant recipients who subsequently underwent ERCP. The following variables were extracted from the medical record: age, sex, transplant etiology; type of biliary anastomosis at transplantation (duct-to-duct vs Roux-en-Y hepaticojejunostomy); prior endoscopic sphincterotomy (EST); use of pre-cut (needle-knife) sphincterotomy at the index ERCP; placement of a common bile duct stent; maintenance immunosuppressive regimen; post-procedure antibiotic use; ERCP indication; number of ERCP sessions; and occurrence of PEP. A multivariable logistic-regression analysis was perfomed to identify determinants of PEP.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 1,338 liver transplant recipients who underwent ERCP were screened, of whom 274 patients with complete clinical and follow-up data were included in the final analysis, comprising 1,174 ERCP sessions. Post-ERCP pancreatitis (PEP) occurred in 66 patients, yielding an overall incidence of 5.6%. Age, sex, graft lobe, biliary anastomosis type, stent placement, and maintenance immunosuppressive regimen were not associated with PEP (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Precut sphincterotomy was significantly more frequent among patients who developed PEP and was independently associated with increased risk in multivariable analysis (adjusted OR 2.72, 95% CI 1.37\u0026ndash;5.42; p\u0026thinsp;=\u0026thinsp;0.004). In contrast, a history of prior endoscopic sphincterotomy was independently protective (adjusted OR 0.43, 95% CI 0.22\u0026ndash;0.84; p\u0026thinsp;=\u0026thinsp;0.013).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePost-ERCP pancreatitis occurred in about 5% of liver transplant recipients in this cohort. Precut sphincterotomy significantly increased the risk, while prior endoscopic sphincterotomy appeared protective. Immunosuppressive therapy was not associated with pancreatitis risk. These findings highlight that procedural factors, rather than immunosuppressive agents, are the main drivers of post-ERCP pancreatitis in this population and emphasize the need for careful cannulation techniques.\u003c/p\u003e","manuscriptTitle":"The Effect of Immunsuppressive Treatment Agents on Post-ERCP Pancreatitis in Living Donor Liver Transplant Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-23 09:33:18","doi":"10.21203/rs.3.rs-8661362/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-22T15:38:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"21842780892679601188862017105079760810","date":"2026-02-22T01:44:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-18T18:20:36+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-27T07:17:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-26T14:32:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-26T14:32:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2026-01-21T14:50:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ae2e90e5-64a1-4aef-bbc1-7a81c6b320df","owner":[],"postedDate":"February 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T09:33:19+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-23 09:33:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8661362","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8661362","identity":"rs-8661362","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}