Randomized Trial of Prophylactic Antibiotics for Endoscopic Retrograde Cholangiopancreatography in Patients With Biliary Obstruction.

INTRODUCTION: The incidence of postendoscopic retrograde cholangiopancreatography (ERCP) infections is reported to be up to 18% in patients with biliary obstruction. Antibiotic prophylaxis may reduce the risk of infectious complications after ERCP; however, the clinical value of prophylactic antibiotics in ERCP remains controversial. METHODS: We conducted a double-blind, placebo-controlled, randomized trial to investigate whether the use of prophylactic antibiotics would reduce infectious complications after ERCP in patients with biliary obstruction. We randomly assigned patients in a 1:1 ratio to receive either a single dose of 1 g intravenous cefoxitin or normal saline as a placebo 30 minutes before undergoing ERCP. The primary outcome was the incidence of infectious complications after ERCP. RESULTS: We enrolled 378 patients, and 189 patients were assigned to each group. The risk of infectious complications after ERCP was 2.8% (5 of 176 patients) in the antibiotic prophylaxis group and 9.8% (17 of 173 patients) in the placebo group (risk ratio, 0.29; 95% confidence interval [CI], 0.11-0.74, P = 0.0073). The incidence rates of bacteremia were 2.3% (4 of 176 patients) and 6.4% (11 of 173 patients), respectively (risk ratio, 0.36; 95% CI, 0.12-1.04; P = 0.0599). The incidence rate of cholangitis was 1.7% (3 of 176 patients) in the antibiotic prophylaxis group and 6.4% (11 of 173 patients) in the placebo group (risk ratio, 0.27; 95% CI, 0.08-0.87; P = 0.0267). DISCUSSION: Antibiotic prophylaxis before ERCP in patients with biliary obstruction resulted in a significantly lower risk of infectious complications, especially cholangitis, than placebo ( ClinicalTrials.gov trial number NCT02958059).

Long-term prognosis and risk factors associated with post-ERCP pneumobilia in patients with common bile duct stones.

BACKGROUND AND AIMS: Post-ERCP pneumobilia is not uncommon; however, studies focusing on the long-term prognosis of patients with post-ERCP pneumobilia are limited. This study aimed to explore long-term prognosis and risk factors associated with post-ERCP pneumobilia in patients with common bile duct stones (CBDSs). METHODS: We conducted a retrospective analysis of 1380 patients who underwent ERCP for CBDSs at our hospital from January 2010 to December 2017. Patients were selected based on inclusion and exclusion criteria and divided into pneumobilia and nonpneumobilia groups, followed by propensity score matching. The matched groups were then compared in terms of incidence rates of both single and multiple recurrences of CBDSs, acute cholangitis, and acute cholecystitis. Multivariate logistic regression analysis was used to explore risk factors associated with pneumobilia. RESULTS: After propensity matching, there was no significant difference in the rate of single recurrence of CBDSs (22.5% vs 30%; P = .446) between the pneumobilia and nonpneumobilia groups. However, the incidences of multiple recurrences of CBDSs (32.5% vs 12.5%; P = .032) and acute cholangitis without stone recurrence (32.5% vs 2.5%; P = <.001) were significantly higher in the pneumobilia group. Based on multivariate logistic regression analysis, in addition to a dilated CBD (diameter of >1 cm) (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.03-3.76; P = .043), endoscopic sphincterotomy with moderate incision (OR, 5.38; 95% CI, 1.14-25.47; P = .034) and with large incision (OR, 8.7; 95% CI, 1.83-41.46; P = .007) were identified as independent risk factors for pneumobilia after initial ERCP. CONCLUSIONS: Patients with post-ERCP pneumobilia have increased risk of multiple recurrences of CBDSs and acute cholangitis without stone recurrence. Independent risk factors for pneumobilia include peripapillary diverticulum, a dilated CBD (>1 cm), and endoscopic sphincterotomy with moderate and large incisions. A normal-sized CBD appears to serve as a secondary barrier against enterobiliary reflux, necessitating further research for confirmation.

The prevalence and impact of small intestine bacterial overgrowth in biliary atresia patients.

BACKGROUND: Acute cholangitis is an ominous complication in biliary atresia (BA) patients. We investigated the prevalence of small intestine bacterial overgrowth (SIBO) in BA patients and its role in predicting acute cholangitis. METHODS: There are 69 BA patients with native liver recruited into this study prospectively. They received hydrogen and methane-based breath testing (HMBT) to detect SIBO after recruitment and were followed prospectively in our institute. RESULTS: There are 16 (23.19%) subjects detected to have SIBO by HMBT. BA subjects with SIBO were noted to have higher serum alanine aminotransferase levels than others without SIBO (P = 0.03). The risk of acute cholangitis is significantly higher in BA patients with SIBO than in others without SIBO (62.50% vs. 15.09%, P < 0.001). The logistic regression analysis demonstrated that BA subjects with SIBO have a higher risk of acute cholangitis than others without SIBO (odds ratio = 9.38, P = 0.001). Cox's proportional hazard analysis further confirmed the phenomena in survival analysis (hazard ratio = 6.43, P < 0.001). CONCLUSIONS: The prevalence of SIBO in BA patients is 23.19% in this study. The presence of SIBO is associated with the occurrence of acute cholangitis in BA patients. IMPACT: What is the key message of your article? Acute cholangitis is common in BA, and is associated with SIBO after hepatoportoenterostomy in this study. What does it add to the existing literature? This study demonstrated that SIBO is common in BA after hepatoportoenterostomy, and is predictive of acute cholangitis and elevated serum ALT levels in BA. What is the impact? This prospective cohort study provides data regarding the significance of SIBO on the risk of acute cholangitis in BA patients.

Epidemiology of biliary tract-associated bloodstream infections and adequacy of empiric therapy: an Australian population-based study.

PURPOSE: Although the biliary tract is a common source of invasive infections, the epidemiology of cholangitis- and cholecystitis-associated bloodstream infection (BSI) is not well defined. The objective of this study was to determine the incidence, clinical determinants, microbiology of biliary tract-associated BSI, and predicted adequacy of common empiric therapy regimens. METHODS: All biliary tract-associated BSI in Queensland during 2000-2019 were identified using state-wide data sources. Predicted adequacy of empiric antimicrobial therapy was determined according to microbiological susceptibility data. RESULTS: There were 3,698 episodes of biliary tract-associated BSI occurred in 3,433 patients of which 2,147 (58.1%) episodes were due to cholangitis and 1,551 (41.9%) cholecystitis, for age- and sex-standardized incidence rates of 2.7, and 2.0 per 100,000 population, respectively. An increasing incidence of biliary tract-associated BSI was observed over the study that was attributable to an increase in cholangitis cases. There was a significant increased risk for biliary tract-associated BSI observed with advancing age and male sex. Patients with cholangitis were older, more likely to have healthcare associated infection, and have more comorbidities most notably liver disease and malignancies as compared to patients with cholecystitis. The distribution of infecting pathogens was significantly different with polymicrobial aetiologies more commonly observed with cholangitis (18.4% vs. 10.5%; p < 0.001). The combination of ampicillin/gentamicin/metronidazole was predicted to have the overall highest adequacy (96.1%), whereas amoxicillin/clavulanate had the lowest (77.0%). Amoxicillin/clavulanate (75.2% vs. 79.4%, p:0.03) and ceftriaxone/metronidazole (83.4% vs. 89.6%; p < 0.001) showed significantly inferior predicted adequacy for cholangitis as compared to cholecystitis. CONCLUSIONS: Bloodstream infections related to cholecystitis and cholangitis exhibit different epidemiology, microbiology, and requirements for empiric therapy.

Endoscopic retrograde cholangiopancreatography-obtained bile culture in acute cholangitis: retrospective analysis of bile cultures and risk factors in a tertiary care center.

BACKGROUND: Collection of bile aspirate during endoscopic retrograde cholangiopancreatography (ERCP) is essential to identify pathogens responsible for acute cholangitis. Limited data are available on the risk factors for the presence of multidrug-resistant organisms (MDRO) in bile. METHODS: We conducted this retrospective, single-center study to assess the prevalence and susceptibility rates of bacteria in bile cultures, and the risk factors for the presence of pathogens, MDRO, and fungi in bile. All consecutive patients who underwent biliary drainage for acute cholangitis from January 2017 to December 2019 were included. RESULTS: 443/1610 ERCPs were performed for acute cholangitis. Bile culture was collected in 91.4% (405/443), of which 86.7% were positive. Most common isolates were Enterococcus faecalis (37.6%) and Escherichia coli (32.8%). Vancomycin resistance was found in 9.9% of Enterococcus species (spp.); extended-spectrum beta-lactamases (ESBL) and carbapenemases in 11.2% and 0.9% of Enterobacteriaceae, respectively. The empiric antimicrobial therapy was changed in 26.4% (n = 107) of cases, with a clinical response in 90.7%. In multivariate analysis, biliary stenting was an independent risk factor for positive bile culture (odds ratio [OR] 9.43; P < 0.01). Independent risk factors for MDRO in bile were patient age>60 years (OR 2.51; P = 0.03), previous sphincterotomy (OR 2.57; P = 0.02), and biliary stenting (OR 2.80; P < 0.01). Previous sphincterotomy was the only risk factor for isolation of fungi in bile (OR 1.61; P = 0.04). CONCLUSIONS: Our study showed an increasing prevalence of Enterococcus spp. and MDRO. Bile cultures should be routinely collected in cholangitis and in patients with repeated ERCPs to allow more efficient antimicrobial treatment.

Comparative Risks of Post-ERCP Adverse Events in Patients with Asymptomatic and Symptomatic Choledocholithiasis: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is the standard of care for the management of choledocholithiasis but carries risk of complications which may result in significant morbidity and mortality. While currently available guidelines endorse the use of ERCP for the management of symptomatic common bile duct stones, the need for ERCP in incidentally found asymptomatic choledocholithiasis is more controversial, and practice varies on a geographic and institutional level. This systematic review and meta-analysis is conducted to compare post-ERCP adverse events between asymptomatic and symptomatic choledocholithiasis patients. METHODS: We searched PubMed/Embase/Web of Science databases to include all studies comparing post-ERCP outcomes between asymptomatic and symptomatic choledocholithiasis patients. The primary outcome was post-ERCP pancreatitis (PEP), while secondary outcomes included post-ERCP cholangitis, bleeding, and perforation. We calculated pooled risk ratios (RR) and 95% confidence intervals (CIs) using the Mantel-Haenszel method within a random-effect model. RESULTS: Our analysis included six observational studies, totaling 2,178 choledocholithiasis patients (392 asymptomatic and 1786 symptomatic); 53% were female. Asymptomatic patients exhibited a higher risk of PEP compared with symptomatic patients (11.7% versus 4.8%; RR 2.59, 95% CI 1.56-4.31, p ≤ 0.001). No significant difference was observed in post-ERCP cholangitis, bleeding, or perforation rates between the two groups. CONCLUSIONS: Asymptomatic patients with choledocholithiasis appear to have a higher risk of PEP than symptomatic patients, while the risk of other post-ERCP adverse events is similar between the two groups. Interventional endoscopists should thoroughly discuss potential adverse events (particularly PEP) with asymptomatic patients before performing ERCP and utilize PEP-prevention measures more liberally in this subgroup of patients.

Long-term outcomes of choledochoduodenostomy for choledocholithiasis: increased incidence of postoperative cholangitis after total or distal gastrectomy.

PURPOSE: Choledochoduodenostomy (CDD) is performed to treat choledocholithiasis (CDL) cases where endoscopic stone removal is difficult. Recognizing CDD characteristics is important for CDL treatment planning. METHODS: A total of 116 patients, including 33 patients ≥ 80 years old (29 with previous total gastrectomy, 19 with previous distal gastrectomy, 20 with built-up stones, 19 with periampullary diverticulum, 10 with confluence stones, 8 with repetitive recurrent stones, 4 with hard stones, 3 with endoscopic retrograde cholangiography [ERC] not available due to lack of cooperation, 2 with a history of pancreatitis post-ERC, and 2 in whom ERC could not be performed due to a disturbed anatomy) underwent CDD for CDL. Postoperative complications and long-term outcomes were evaluated. RESULTS: The in-hospital mortality rate was 0%. The morbidity (grade ≥ IIIA according to the Clavien-Dindo classification) rates in the elderly (≥ 80 years old) and non-elderly (51-79 years old) patients were 3.0% (1/33) and 2.4% (2/83), respectively (p = 0.85). Long-term complications included cholangitis in eight (7%) patients, of which three cases were repetitive and seven had an operative history of total or distal gastrectomy. The incidence of postoperative cholangitis after total or distal gastrectomy was 15% (7/48), which was significantly higher than that involving other causes (1.5%, 1/68; p < 0.01). Two patients with cholangitis after total gastrectomy experienced early recurrence of lithiasis at 2 and 9 months after surgery. CONCLUSIONS: CDD is safe, even in elderly patients. However, a history of total gastrectomy or distal gastrectomy may increase the incidence of postoperative cholangitis.

Real-life patency of plastic biliary stents in the pandemic era: is stent removal after 6 months safe and effective?

BACKGROUND: The SARS-CoV-2 pandemic conditioned the optimal timing of some endoscopic procedures. ESGE guidelines recommend replacement or removal of the plastic biliary stents within 3-6 months to reduce the risk of complications. Our aim was to analyse the outcomes of patients who had delayed plastic biliary stent removal following endoscopic retrograde cholangiopancreatography (ERCP) in the pandemic era. METHODS: Retrospective study including consecutive ERCPs with plastic biliary stent placement between January 2019 and December 2021. Delayed removal was defined as presence of biliary stent >6 months after ERCP. The evaluated outcomes were stent migration, stent dysfunction, obstructive jaundice, cholangitis, acute pancreatitis, hospitalization, and biliary pathology-related mortality. RESULTS: One-hundred and twenty ERCPs were included, 56.7% male patients, with a mean age of 69.4 ± 15.7 years. Indications for plastic biliary stent insertion were choledocholithiasis (72.5%), benign biliary stricture (20.0%), and post-cholecystectomy fistula (7.5%). Delayed stent removal occurred in 32.5% of the cases. The median time to stent removal was 3.5 ± 1.3 months for early removal and 8.6 ± 3.1 months for delayed removal. Patients who had delayed stent removal did not have a significantly higher frequency of stent migration (20.5 vs 11.1%, p = 0.17), stent dysfunction (17.9 vs 13.6%, p = 0.53), hospitalization (17.9 vs 14.8%, p = 0.66), obstructive jaundice (2.6 vs 0.0%, p = 0.33), cholangitis (10.3 vs 13.6%, p = 0.77), acute pancreatitis (0.0 vs 1.2%, p = 1.0), or biliary pathology-related mortality (2.6 vs 1.2%, p = 0.55). CONCLUSIONS: Delayed plastic biliary stent removal does not seem to have a negative impact on patients' outcomes. In the current pandemic situation, while scheduled endoscopic procedures may have to be postponed, elective removal of plastic biliary stents can be safely deferred.

Risk Factors for Cholangitis After Pancreatoduodenectomy: A Systematic Review.

BACKGROUND: Cholangitis is a late complication after pancreatoduodenectomy with considerable clinical impact and is difficult to treat. The aim of this systematic review was to provide an overview of the literature identifying risk factors for postoperative cholangitis. METHODS: A systematic search of the databases PUBMED and EMBASE was performed to identify all studies reporting on possible risk factors for cholangitis following pancreatoduodenectomy. Data on patient, peri- and postoperative characteristics were collected. Risk of bias assessment was done according to the methodological index for non-randomized studies (MINORS) criteria. RESULTS: In total, 464 studies were identified. Eight studies met the inclusion criteria for this analysis. The definition of postoperative cholangitis was inconsistent, with four studies using the Tokyo Guidelines, whereas other studies used different definitions. Data on 26 potential risk factors concerning the patient, peri- and postoperative characteristics were analyzed. Five factors were significantly associated with cholangitis in two or more studies: high body mass index, duration of surgery, benign disease, postoperative pancreatic fistula, and postoperative serum alkaline phosphatase. CONCLUSION: Multiple potential risk factors for postoperative cholangitis were identified, with large discrepancies between studies. Prospective research, with consensus on the definition, is required to determine the true relevance of these risk factors.

Influence of Frailty in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography for Biliary Stone Disease: A Nationwide Study.

BACKGROUND AND AIMS: Pancreaticobiliary diseases are common in the elderly. To this end, frailty represents a state of vulnerability that should be considered when assessing the risks and benefits of therapeutic endoscopic procedures. We aim to determine the rate of readmissions and clinical outcomes using the validated Hospital Frailty Risk Score in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Using the National Readmissions Database, we identified patients with an admission diagnosis of cholangitis with obstructive stone from 2016 to 2019. Patients were determined to be of low frailty risk with a score of < 5, while patients of medium to high frailty risk had a score of > 5. RESULTS: During the study period, 5751 patients were identified with acute cholangitis with obstructing stone. Mean age of index admissions was 69.4 years and 51.8% were female. From the total cohort, 5119 (89.2%) patients underwent therapeutic ERCP, 38.0% (n = 1947) of whom were regarded as frail (risk score > 5). Following ERCP, frail patients had a less but statistically insignificant readmission rate compared to non-frail patients (2.76% vs 4.05%, p = 0.450). However, compared to non-frail patients, frail patients experienced higher post-ERCP complications (6.20% vs 14.63%, p < 0.001). Frail patients were more likely to have longer lengths of stay, higher hospital cost, and mortality risk. CONCLUSION: ERCP is not a risk factor for readmission among frail patients. However, frail patients are at higher risk for procedure-related complications, healthcare utilization, and mortality.

Risk Factors for Recurrence of Cholangitis After Pancreaticoduodenectomy and Comparison of Stents in Hepaticojejunostomy.

BACKGROUND: Postoperative cholangitis is a common complication of pancreaticoduodenectomy. Frequent cholangitis impairs patients' quality of life after pancreaticoduodenectomy. However, the risk factors for recurrence of cholangitis remain unclear. Hence, this retrospective study aimed to identify risk factors for recurrence of cholangitis after pancreaticoduodenectomy. METHODS: The medical records of patients who underwent pancreaticoduodenectomy between 2015 and 2019 in our institution were retrospectively reviewed. At least two episodes of cholangitis a year after pancreaticoduodenectomy were defined as 'recurrence of cholangitis' in the present study. Univariate and multivariate analyses were performed. RESULTS: The recurrence of cholangitis occurred in 40 of 207 patients (19.3%). Multivariate analysis revealed that internal stent (external, RR: 2.16, P = 0.026; none, RR: 4.76, P = 0.011), firm pancreas (RR: 2.61, P = 0.021), constipation (RR: 3.49, P = 0.008), and postoperative total bilirubin>1.7 mg/dL (RR: 2.94, P = 0.006) were risk factors of recurrence of cholangitis. Among patients with internal stents (n = 54), those with remnant stents beyond 5 months had more frequent recurrence of cholangitis (≥5 months, 75%; <5 months, 30%). CONCLUSIONS: Internal stents, firm pancreas, constipation, and postoperative high bilirubin levels are risk factors for cholangitis recurrence after pancreaticoduodenectomy. In addition, the long-term implantation of internal stents may trigger cholangitis recurrence.

Risk factors and outcomes for cholangitis after hepatic resection.

INTRODUCTION: There is a paucity in the literature in regard to the incidence, risk factors, and outcomes for post-operative cholangitis following hepatic resection. METHODS: Retrospective review of the ACS NSQIP main and targeted hepatectomy registries for 2012-2016. RESULTS: A total of 11,243 cases met the selection criteria. The incidence of post-operative cholangitis was 0.64% (151 cases). Multivariate analysis identified several risk factors associated with the development of post-operative cholangitis, stratified out by pre-operative and operative factors. The most significant risk factors were biliary anastomosis and pre-operative biliary stenting with odds ratios (OR) of 32.39 (95% CI 22.91-45.79, P value < 0.0001) and 18.32 (95% CI 10.51-31.94, P value < 0.0001) respectively. Cholangitis was significantly associated with post-operative bile leaks, liver failure, renal failure, organ space infections, sepsis/septic shock, need for reoperation, longer length of stay, increased readmission rates, and death. CONCLUSION: Largest analysis of post-operative cholangitis following hepatic resection. While a rare occurrence, it is associated with significantly increased risk for severe morbidity and mortality. The most significant risk factors were biliary anastomosis and stenting.

Nonalcoholic Fatty Liver Disease as a Risk Factor for Severe Cholangitis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders. Acute cholangitis (AC) is a life-threatening illness. OBJECTIVES: To determine whether NAFLD is a risk factor for the severity of AC. METHODS: We retrospectively studied hospitalized patients with a diagnosis of AC over 5 years. Patients were divided into a NAFLD group and a non-NAFLD group. We compared the two groups with regard to demographic characteristics, co-morbidities, laboratory data, and severity of AC (including Charlson Comorbidity Index [CCI] and Tokyo Consensus meeting criteria). RESULTS: In all, 298 of 419 hospitalized patients diagnosed with AC met the inclusion criteria. Of these, 73/298 (24.5%) were in the NAFLD group. NAFLD group patients were younger and more likely to be diabetic and obese than the non-NAFLD group. Participants in the NAFLD presented with higher serum C-reactive protein and higher liver enzymes (P < 0.05, for each parameter) and with more events of organ dysfunction (P < 0.001) and bacteremia (P < 0.005). Regarding the severity of AC according to Tokyo Consensus, among the NAFLD group more patients presented with Grade II (39.7 vs. 33.3%, P < 0.001) and Grade III (23.3 vs. 18.3, P < 0.001) cholangitis. More Grade I cholangitis was found among the non-NAFLD group (48.4 vs. 37%, P < 0.001). Multivariate logistic regression analysis showed that NAFLD was independently associated with severe AC, Grade III (odds ratio 3.25, 95% confidence interval 1.65-6.45, P = 0.038). CONCLUSIONS: NAFLD is an independent risk factor for the severity of AC.

Increased post-endoscopic retrograde cholangiopancreatography pancreatitis for choledocholithiasis without acute cholangitis.

BACKGROUND AND AIM: Choledocholithiasis is the most common indication for endoscopic retrograde cholangiopancreatography (ERCP). Identifying risk factors for post-ERCP pancreatitis (PEP) is important for reducing the risk of developing PEP after common bile duct (CBD) stone removal. However, studies examining the risk factors for PEP for CBD stones are scarce. The aim of this study was to examine whether the presence or absence of acute cholangitis is a clinical risk factor for PEP in patients with CBD stones. METHODS: In this multicenter retrospective study, 1539 patients with naïve papillae were divided into patients without and with acute cholangitis. We compared the incidence of PEP between the two groups using one-to-one propensity score matching to adjust for the potential confounding factors of PEP. RESULTS: In the entire cohort, the rates of PEP in patients without and with acute cholangitis were 9.6% (52/542) and 1.8% (18/997), respectively (P < 0.001, odds ratio = 5.8). In the propensity-matched cohort, the rates of PEP in patients without and with acute cholangitis were 8.3% (27/326) and 2.5% (8/326), respectively (P = 0.002, odds ratio = 3.6). The rate of PEP was significantly higher in patients without acute cholangitis than in those with acute cholangitis after adjusting for the confounding factors of PEP. CONCLUSIONS: The absence of acute cholangitis may be an important clinical risk factor for PEP due to CBD stone removal. In patients without acute cholangitis, endoscopists should explain the specific risk of PEP carefully and actively implement prophylaxis against PEP.

Peri-ampullary diverticulum was associated with a higher rate of acute cholangitis among patients with choledocholithiasis.

BACKGROUND: Choledocholithiasis is a commonly encountered disease that is associated with various clinical presentations ranging from mild form of biliary colic to severe life-threatening acute cholangitis. Recently, peri-ampullary diverticulum (PAD) has been linked to the development of biliary diseases; however, data regarding its association with the development of acute cholangitis in the setting of choledocholithiasis are scarce. AIMS: We aimed to identify predictors, specifically PAD, for the development of acute cholangitis in patients with choledocholithiasis. METHODS: We performed a retrospective cross-sectional study of all patients admitted to Galilee Medical Center from 1 January 2010 to 31 December 2019 with different clinical presentations of documented choledocholithiasis including cholangitis, biliary pancreatitis, and biliary colic with abnormal liver enzymes. RESULTS: Overall, 651 patients were included in the final analysis. Among them, 88 patients (13.5%) had choledocholithiasis associated with acute cholangitis (group A), as compared to 563 patients (86.5%) without acute cholangitis (group B). The average ages in groups A and B were 77.8 ± 13.6 and 62.4 ± 20.4 years, respectively (P < 0.0001). The rate of PAD was significantly higher in group A as compared to group B (35.2% vs. 19%, P = 0.0002). However, the rate of smoking, chronic liver diseases, hemolytic anemia, and post-cholecystectomy status were not different between the groups (P = 0.3, P = 0.3, P = 0.2, and P = 0.3), respectively. On univariate analysis, age (OR 1.05, P < 0.0001) and PAD (OR 2.32, P = 0.0006) were significantly associated with acute cholangitis. On multivariate logistic regression analysis, the effects of age and PAD were preserved (OR 1.05, 95% CI 1.03-1.07, P < 0.0001 and OR 1.64, 95% CI 1.02-2.72, P = 0.049), respectively. CONCLUSION: PAD showed a significant association with the development of acute cholangitis among patients with choledocholithiasis. Identification of gallbladder and biliary stones in patients with PAD is of paramount importance since early diagnosis and treatment might prevent further life-threatening complications.

Disease-Based Risk Stratification of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis for Common Bile Duct Stones.

BACKGROUND: Risk stratification of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) for common bile duct (CBD) stones is needed for clinicians to adequately explain to patients regarding the risk of PEP in advance of ERCP and to proactively take preventive measures in high-risk patients. AIMS: To stratify the risk of PEP for CBD stones based on CBD-related diseases. METHODS: A total of 1551 patients with naïve papilla who underwent ERCP for CBD stones were divided into three groups: Group A: asymptomatic CBD stones, Group B: obstructive jaundice and elevated liver test values without cholangitis, and Group C: mild, moderate, and severe cholangitis. We stratified the risk of PEP by comparing its incidence among the three groups using the Holm's method. Furthermore, we performed one-to-one propensity score matching between Group A and the other groups to examine the risk of PEP in Group A. RESULTS: The incidence rates in Groups A, B, and C were 13.7%, 7.3%, and 1.8%, respectively. The Holm-adjusted p values between Groups A and B, Groups A and C, and Groups B and C were 0.023, < 0.001, and < 0.001, respectively. Propensity score matching revealed that the incidence of PEP was significantly more in Group A than in the other groups (13.3% vs. 1.5%; p < 0.001). CONCLUSIONS: The risk of PEP for CBD stones was stratified into low risk (Group C), intermediate risk (Group B), and high risk (Group A). This simple disease-based risk stratification may be useful to predict the risk of PEP in advance of ERCP.

Blood cultures should be collected for acute cholangitis regardless of severity.

BACKGROUND: Despite the high frequency of bacteremia in acute cholangitis, the indications for blood cultures and the relationship between the incidence of bacteremia and severity of acute cholangitis have not been well established. This study examined the association between the 2018 Tokyo Guidelines (TG18) severity grading for acute cholangitis and incidence of bacteremia to identify the need for blood cultures among patients with acute cholangitis in each severity grade. METHODS: Patients with acute cholangitis who visited our emergency department between 2019 and 2020 were retrospectively investigated. Patients administered antibiotics within 48 h of hospital arrival, whose prothrombin time-international normalized ratios were not measured, or who were suspected of false bacteremia were excluded. RESULTS: Out of the included 358 patients with acute cholangitis, blood cultures were collected from 310 (87%) patients, of which 148 (48%) were complicated with bacteremia. As the TG18 severity grading increased, the frequency of bacteremia increased (Grade I, 35% [59/171]; Grade II, 59% [48/82]; Grade III, 74% [42/57]; P <0.001). Agreement with the TG18 diagnostic criteria (unfulfilled, suspected, or definite) was not different between patients with and without bacteremia; however, 36% (14/39) of the patients with "unfulfilled" criteria were complicated with bacteremia. CONCLUSIONS: As the severity of acute cholangitis increased, the frequency of bacteremia increased; however, the incidence of bacteremia was high even in mild cases and cases that did not meet the TG18 diagnostic criteria. Blood cultures should be collected regardless of the severity of acute cholangitis for patients who visit the emergency department.

Microbiological analysis of patients with first and recurrent episodes of acute cholangitis in a middle-sized hospital: A single-center retrospective study in rural North Kyoto, Japan.

BACKGROUND: Knowledge of the bacterial spectrum involved in acute cholangitis is essential for adequate empiric antibiotic treatment. There is a lack of published data comparative data between patients with first and recurrent episodes of acute cholangitis. This study aimed to analyze the microbial spectrum in patients with first and second episodes of acute cholangitis. METHODS: We retrospectively assessed 251 patients with first episodes of acute cholangitis between January 2014 to September 2020. RESULTS: At the first episode of acute cholangitis, the predominant strains belonged to Escherichia coli (17.9%), followed by Klebsiella spp. (15.5%), Enterobacter spp. (6.4%), and Enterococcus spp. (5.6%). During follow-up, acute cholangitis recurred in 109 patients; at the second episode, the predominant strains belonged to Enterococcus spp. (35.8%), followed by Klebsiella spp. (27.5%), Enterobacter spp. (22.9%), and Escherichia coli (15.6%). Enterococcus spp. were the most common pathogen in patients with second episode of acute cholangitis, regardless of whether the cholangitis was caused by a malignant tumor or a benign disease. CONCLUSIONS: Unlike in patients with a first episode of acute cholangitis, clinicians should consider empirical treatment with anti-enterococcal antibiotics in patients with recurrent episodes of acute cholangitis.

Concomitant extrahepatic autoimmune diseases do not compromise the long-term outcomes of primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) patients often have concomitant extrahepatic autoimmune (EHA) diseases including Sjögren's syndrome (SS), systemic sclerosis (SSc), rheumatoid arthritis (RA), and autoimmune thyroid disease. The present study aimed to describe the prevalence of EHA diseases in PBC and explore the impact of EHA diseases on the long-term outcomes of PBC in Chinese patients. METHODS: Medical records of PBC patients diagnosed in our institute were retrospectively reviewed. Patients were followed up by a standardized telephone interview. The endpoints were defined as liver-related death and/or liver transplantation. RESULTS: Totally 247 of the 985 (25.1%) PBC patients enrolled in the study had at least one concomitant EHA disease. Sjögren's syndrome (n = 140, 14.2%) was the most frequent one, followed by rheumatoid arthritis (RA) (n = 56, 5.7%) and Hashimoto's thyroiditis (n = 45, 4.6%). Patients with EHA diseases were more common in females (P < 0.001) and in those with a family history of autoimmune disease (P = 0.017). Overall, no differences were found between PBC patients with and without EHA diseases in terms of biochemical response rates to ursodeoxycholic acid, the incidence of hepatic events, or transplant-free survival. RA and EHA ≥ 2 were protective factors for hepatic events in univariate Cox analysis, but the results became insignificant in multivariate analysis. CONCLUSIONS: Concomitant EHA diseases were common in PBC patients but did not compromise the long-term outcomes of PBC.

Clinical aspects and prognosis of patients with inflammatory bowel disease associated with autoimmune liver diseases.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are chronic conditions that may be accompanied by autoimmune liver disease (AILD), most commonly primary sclerosing cholangitis (PSC). The objective of this study was to evaluate the behaviour of patients with IBD associated with AILD and compare a PSC group with a non-PSC group. METHODS: Medical records of patients with IBD associated with PSC, autoimmune cholangitis, primary biliary cholangitis, small-duct PSC, autoimmune hepatitis (AIH) and overlapping syndromes were assessed. RESULTS: Fifty-four patients were included: 48 (88.9%) had ulcerative colitis and six (11.1%) had Crohn's disease; 35 (64.8%) had PSC and 19 (35.2%) did not have PSC. There was no difference in outcomes (surgical treatment for IBD, liver transplantation or death) between the groups. Time since the diagnosis of IBD was associated with surgical treatment of IBD (p=0.041; OR: 1.139, 95% CI: 1.006-1.255). Time since the diagnosis of AILD (p=0.003; OR: 1.259, 95% CI: 1.1-1.396), as well as portal hypertension at diagnosis (p=0.014; OR: 18.22, 95% CI: 1.815-182.96), were associated with liver transplantation. In addition, previous diagnosis of AIH was associated with de novo IBD (p=0.012; OR: 7.1, 95% CI: 1.215-42.43). CONCLUSION: Both groups had similar disease behaviour. A longer time since the diagnosis of IBD increased the risk for surgical treatment (13.9%/year). A 25.9%/year increase in liver transplantation was observed after the diagnosis of AILD, which was increased 18.22 times by the presence of portal hypertension. In addition, the diagnosis of AIH was associated with an increase in the number of diagnoses of de novo IBD (7.1).