Association of preoperative cholangitis with outcomes and expenditures among patients undergoing pancreaticoduodenectomy.

BACKGROUND: This study aimed to characterize the association of preoperative acute cholangitis (PAC) with surgical outcomes and healthcare costs. METHODS: Patients who underwent pancreaticoduodenectomy (PD) between 2013 and 2021 were identified using 100% Medicare Standard Analytic Files. PAC was defined as the occurrence of at least 1 episode of acute cholangitis within the year preceding surgery. Multivariable regression analyses were used to compare postoperative outcomes and costs relative to PAC. RESULTS: Among 23,455 Medicare beneficiaries who underwent PD, 2,217 patients (9.5%) had at least 1 episode of PAC. Most patients (n = 14,729 [62.8%]) underwent PD for a malignant indication. On multivariable analyses, PAC was associated with elevated odds of surgical site infection (odds ratio [OR], 1.14; 95% CI, 1.01-1.29), sepsis (OR, 1.17; 95% CI, 1.01-1.37), extended length of stay (OR, 1.13; 95% CI, 1.01-1.26), and readmission within 90 days (OR, 1.14; 95% CI, 1.04-1.26). Patients with a history of PAC before PD had a reduced likelihood of achieving a postoperative textbook outcome (OR, 0.83; 95% CI, 0.75-0.92) along with 87.8% and 18.4% higher associated preoperative and postoperative healthcare costs, respectively (all P < .001). Overall costs increased substantially among patients with more than 1 PAC episode ($59,893 [95% CI, $57,827-$61,959] for no episode vs $77,922 [95% CI, $73,854-$81,990] for 1 episode vs $101,205 [95% CI, $94,871-$107,539] for multiple episodes). CONCLUSION: Approximately 1 in 10 patients undergoing PD experienced an antecedent PAC episode, which was associated with adverse surgical outcomes and greater healthcare expenditures.

Hepatolithiasis: Epidemiology, presentation, classification and management of a complex disease.

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts, above the hilar confluence of the hepatic ducts. The disease is more prevalent in Asia, mainly owing to socioeconomic and dietary factors, as well as the prevalence of biliary parasites. In the last century, owing to migration, its global incidence has increased. The main pathophysiological mechanisms involve cholangitis, bile infection and biliary strictures, creating a self-sustaining cycle that perpetuates the disease, frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of "recurrent pyogenic cholangitis". Furthermore, long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma. Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment. The management of symptomatic patients and those with complications can be complex, and relies upon a multidisciplinary team of hepatologists, endoscopists, interventional radiologists and hepatobiliary surgeons, with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications. This comprehensive review provides insight on various aspects of hepatolithiasis, with a focus on epidemiology, new evidence on pathophysiology, most important clinical aspects, different classification systems and contemporary management.

Pharmacotherapy for primary biliary cholangitis: an assessment of medication candidacy and rates of treatment.

BACKGROUND: Ursodeoxycholic acid is the preferred first-line therapy for primary biliary cholangitis. Alternative therapies, such as obeticholic acid, are recommended for patients who cannot tolerate ursodeoxycholic acid or who have an inadequate response to ursodeoxycholic acid monotherapy. Prior investigations have suggested that as many as 30% of patients with primary biliary cholangitis may have never received treatment with ursodeoxycholic acid. No prior investigations have examined usage rates of obeticholic acid in the treatment of primary biliary cholangitis. METHODS: All patients with an ICD-10 diagnosis of primary biliary cholangitis who had any records within the health system were included. A review of medical records was performed to confirm the diagnosis of primary biliary cholangitis and determine which medications had been prescribed for treatment, as well as candidacy for second-line therapies. RESULTS: A total of 495 patients met inclusion criteria. Notably, 95% of patients were taking ursodeoxycholic acid for treatment of their primary biliary cholangitis, with 67% of patients having disease that was well-controlled on ursodeoxycholic acid monotherapy. In total, 8% of patients were taking obeticholic acid (either as combination or monotherapy). Only 3% would benefit from the addition of a second line therapy but had not yet been offered medication. Only 3% of patients were not on any medication for management of their primary biliary cholangitis. CONCLUSIONS: Ursodeoxycholic acid is a readily available and generally well-tolerated medication that should be offered to all patients with primary biliary cholangitis as first-line therapy. While prior investigations have suggested that up to 30% of patients with primary biliary cholangitis may never have received treatment for the disorder, the present study suggests that patients are generally being managed according to guidelines. Moreover, a significant proportion of patients with primary biliary cholangitis will qualify for second line therapies and prescribers should be aware of the indications to use these medications.

Severity assessment to guide empiric antibiotic therapy for cholangitis in children after Kasai portoenterostomy: a multicenter prospective randomized control trial in China.

BACKGROUND: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. RESULTS: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P >0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. CONCLUSIONS: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.

Short vs long-course antibiotic therapy in adults with acute cholangitis: A systematic review, meta-analysis, and evidence quality assessment.

BACKGROUND: Acute cholangitis (AC) constitutes an infection with increased mortality rates in the past. Due to new diagnostic tools and therapeutic methods, the mortality of AC has been significantly reduced nowadays. The initial antibiotic treatment of AC has been oriented to the most common pathogens connected to this infection. However, the optimal duration of the antibiotic treatment of AC is still debatable. AIM: To investigate if shorter-course antibiotic treatments could be similarly effective to long-course treatments in adults with AC. METHODS: This study constitutes a systematic review and meta-analysis of the existing literature concerning the duration of antibiotic therapy of AC and an assessment of the quality of the evidence. The study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analyses. Fifteen studies were included in the systematic review, and eight were eligible for meta-analysis. Due to heterogeneous duration cutoffs, three study-analysis groups were formed, with a cutoff of 2-3, 6-7, and 14 d. RESULTS: A total of 2763 patients were included in the systematic review, and 1313 were accounted for the meta-analysis. The mean age was 73.66 ± 14.67 years, and the male and female ratio was 1:08. No significant differences were observed in the mortality rates of antibiotic treatment of 2-3 d, compared to longer treatments (odds ratio = 0.78, 95% confidence interval: 0.23-2.67, I2 = 9%) and the recurrence rates and hospitalization length were also not different in all study groups. CONCLUSION: Short- and long-course antibiotic treatments may be similarly effective concerning the mortality and recurrence rates of AC. Safe conclusions cannot be extracted concerning the hospitalization duration.

Racial and Ethnic Disparities Among Patients Hospitalized for Acute Cholangitis in the United States.

GOALS: We sought to determine whether race/ethnicity is associated with hospitalization outcomes among patients admitted with acute cholangitis. BACKGROUND: Few studies have evaluated the association between race and outcomes in patients with acute cholangitis. STUDY: We analyzed United States hospitalizations from 2009 to 2018 using the Nationwide Inpatient Sample (NIS). We included patients 18 years old or above admitted with an ICD9/10 diagnosis of cholangitis. Race/ethnicity was categorized as White, Black, Hispanic, or Other. We used multivariable regression to determine the association between race/ethnicity and in-hospital outcomes of interest, including endoscopic retrograde cholangiopancreatography (ERCP), early ERCP (<48 h from admission), length of stay (LOS), and in-hospital mortality. RESULTS: Of 116,889 hospitalizations for acute cholangitis, 70% identified as White, 10% identified as Black, 11% identified as Hispanic, and 9% identified as Other. The proportion of non-White patients increased over time. On multivariate analysis controlling for clinical and sociodemographic variables, compared with White patients, Black patients had higher in-hospital mortality (adjusted odds ratio: 1.4, 95% confidence interval: 1.2-1.6, P <0.001). Black patients were also less likely to undergo ERCP, more likely to undergo delayed ERCP, and had longer LOS ( P <0.001 for all). CONCLUSIONS: In this contemporary cohort of hospitalized patients with cholangitis, Black race was independently associated with fewer and delayed ERCP procedures, longer LOS, and higher mortality rates. Future studies with more granular social determinants of health data should further explore the underlying reasons for these disparities to develop interventions aimed at reducing racial disparities in outcomes among patients with acute cholangitis.

Longitudinal Assessment of Bile Duct Loss in Primary Biliary Cholangitis.

INTRODUCTION: Bile duct involvement is a key finding of primary biliary cholangitis (PBC). The aim of this study was to evaluate baseline ductopenia and disease progression. METHODS: Retrospective longitudinal histological follow-up of treatment-naive patients with PBC. RESULTS: Eighty-three patients were included, with ductopenia correlated to fibrosis stage at baseline. The cumulative incidence of severe ductopenia remained stable after 5 years, whereas fibrosis continually increased over time. Baseline AST-to-Platelet Ratio Index and elevated alkaline phosphatase >2 times the normal with abnormal bilirubin were associated with ductopenia progression. DISCUSSION: Bile duct injury does not seem to follow the same course as fibrosis in PBC.

Cholecystitis and Cholangitis during Continuous Renal Replacement Therapy in a Patient with Retroperitoneal Hemorrhage Requiring Large Amounts of Contrast Medium for the Assessment and Intervention.

Intravenous use of contrast medium (CM), which may cause kidney dysfunction, is admissible for hemodialysis patients because of the efficient removal by hemodialysis. We herein report a 61-year-old woman on hemodialysis who suffered from cholecystitis and cholangitis after large-volume CM administration during continuous renal replacement therapy. After catheter ablation, she developed life-threatening retroperitoneal hemorrhage, which led to the use of 500 mL CM for 5 consecutive days. It should be kept in mind that excessive vicarious CM excretion in the biliary system may become a predisposing factor of cholecystitis and cholangitis in patients who frequently undergo radiological interventions and imaging.

Impact of Preoperative Cholangitis on Short-term Outcomes Among Patients Undergoing Liver Resection.

BACKGROUND: The impact of preoperative cholangitis (PC) on perioperative outcomes among patients undergoing liver resection remains poorly defined. We sought to characterize the prevalence of PC among patients undergoing hepatectomy and define the impact of PC on postoperative outcomes. METHODS: Patients who underwent liver resection between 2013 and 2015 were identified using the Center for Medicare Services (CMS) 100% Limited Data Set (LDS) Standard Analytic Files (SAFs). Short-term outcomes after liver resection, stratified by the presence of PC, were examined. Subgroup analyses were performed to evaluate the relationship between the timing of liver resection relative to PC. RESULTS: Among 7392 patients undergoing liver resection, 251 patients (3.4%) experienced PC. Patients with PC were more likely to be male (59.0% vs. 50.6%) and to have a benign diagnosis (34.3% vs. 19.8%) compared with patients without PC (both p<0.05). On multivariable analysis, PC was associated with increased odds of experiencing a complication (OR 1.54, 95%CI 1.17-2.03), extended LOS (OR 2.60, 95%CI 1.99-3.39), 90-day mortality (OR 2.31, 95%CI 1.64-3.26), and higher Medicare expenditures (OR 3.32, 95%CI 2.55-4.32). Among patients with PC, requirement of both endoscopic and percutaneous biliary drainage (OR 5.16, 95%CI 1.36-9.61), as well as liver resection < 2 weeks after PC (OR 2.92, 95%CI 1.13-7.57) were associated with higher odds of 90-day mortality. CONCLUSION: Approximately 1 in 30 Medicare beneficiaries undergoing liver resection had a history of PC. PC was associated with an increased risk of adverse short-term outcomes and higher healthcare expenditures among patients undergoing hepatectomy.

Postbiliary drainage rates of cholangitis are impacted by procedural technique for patients with supra-ampullary cholangiocarcinoma: A SEER-Medicare analysis.

BACKGROUND: The optimal approach to biliary drainage for patients with supra-ampullary cholangiocarcinoma remains undetermined. Violation of sphincter of Oddi results in bacterial colonization of bile ducts and may increase postdrainage infectious complications. We sought to determine if rates of cholangitis are affected by the type of drainage procedure. METHODS: We examined the Surveillance, Epidemiology, and End Results-Medicare linked database from 1991 to 2013 for cholangiocarcinoma. Biliary drainage procedures were categorized as sphincter of Oddi violating (SOV) or sphincter of Oddi preserving (SOP). Patients were stratified by resection. RESULTS: A total of 1914 patients were included in the final analysis. A total of 1264 patients did not undergo a postdrainage resection (SOP 83, SOV 1181) while 650 did undergo a postdrainage resection (SOP 26, SOV 624). For those patients not undergoing a postdrainage resection, the rate of cholangitis 90 days after an SOP procedure was 19% compared with 34% in the SOV cohort (P = 0.007). For those patients undergoing a postdrainage resection, the rate of cholangitis 90 days after an SOP procedure was less than 42.3% compared with 30% in the SOV cohort (P = 0.66). CONCLUSION: For patients with supra-ampullary cholangiocarcinoma that did not undergo resection, biliary drainage procedures that violated the sphincter of Oddi were associated with increased rates of cholangitis.

Hospitalization Burden of Biliary Strictures and Cholangitis After Pancreaticoduodenectomy.

BACKGROUND: Postsurgical biliary disease in Roux-en-y and cholecystectomies has been investigated, but less literature exists regarding biliary complications after Whipple procedure (pancreaticoduodenectomy [PD]). Moreover, the hospital burden incurred after this complication has not been previously examined. The aim of this study is to assess the trends in hospitalization for biliary strictures and cholangitis after PD. MATERIALS AND METHODS: The National Inpatient Sample identified all cases with a PD and a primary diagnosis of biliary complication in 2014. Cases were identified using the International Classification of Diseases, Clinical Modification codes. Primary outcomes were association of biliary complications with mortality, cost of admission, and length of stay. RESULTS: A total of 10,145 patients in 2014 were documented with a previous PD. Mortality was 50-fold greater without biliary complications (2.7% versus 0.05%), but a 95% increased length of stay (25.8 d versus 13.2 d, P = 0.014) and 70% increased cost of admission ($293,894 versus $165,862, P = 0.092) occurred with biliary complications. Regression analysis revealed increased length of stay in all cohorts (adjusted odds ratio: 14.3, P = 0.007) and increased cost of admission with cholangitis (adjusted odds: 458283, P = 0.00). Finally, there was increased biliary strictures, cost of hospitalization, and length of stay from 2011 to 2014. CONCLUSIONS: Biliary disease due to the PD appears to longitudinally increase length of stay and cost of hospitalization. Compared with gastrointestinal bleed and delayed gastric emptying, biliary strictures and cholangitis are still very high acuity, requiring more extensive medical resources. Minimally invasive surgeries and robotics could play a vital role in minimizing biliary complications and the ensuing hospitalization burden.

Liver assessment using Gd-EOB-DTPA-enhanced magnetic resonance imaging in primary biliary cholangitis patients.

PURPOSE: To evaluate the feasibility of utilizing gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for the assessment of Child-Pugh class and for differentiating between patients with primary biliary cholangitis (PBC) and posthepatitic cirrhosis. MATERIALS AND METHODS: 45 PBC patients and 45 posthepatitic cirrhosis patients were enrolled and Gd-EOB-DTPA-enhanced MRI was applied. The average relative signal enhancement (RE) of the liver and average contrast to noise ratio (CNR) of common bile duct at 4, 20, and 50 min between different Child-Pugh classes of PBC patients were compared. The RE and CNR in all timepoints in patients with the same Child-Pugh class were compared between PBC patients and posthepatitic cirrhosis patients. RESULTS: The RE of liver and CNR of common bile duct at 4, 20, and 50 min was significantly different between all Child-Pugh classes of PBC patients. There were also no significant differences in the RE of liver and CNR of common bile duct in all timepoints between patients with PBC and posthepatitic cirrhosis in the same Child-Pugh class. CONCLUSION: Gd-EOB-DTPA-enhanced MRI is feasible for liver function assessment in PBC patients. However, the ability of this modality in differentiating liver cirrhosis of different etiologies requires further investigation.

Upper gastrointestinal hemorrhage is associated with poor outcomes among patients with acute cholangitis: a nationwide analysis.

OBJECTIVE: Acute cholangitis (AC) and upper gastrointestinal hemorrhage (UGIH) are common emergencies encountered by gastroenterologists. We aimed to evaluate the impact of UGIH on in-hospital mortality, morbidity and resource utilization among patients with AC. PATIENTS AND METHODS: Adult admissions with a principal diagnosis of AC were selected from the National Inpatient Sample 2010-2014. The exposure of interest was significant UGIH (requiring red blood cell transfusion). The primary outcome was in-hospital mortality. Secondary outcomes were significant UGIH's incidence, morbidity (shock, prolonged mechanical ventilation and total parenteral nutrition), and resource utilization (length of hospital stay and total hospitalization charges and costs). Confounders were adjusted for using propensity matching and multivariate regression analysis. RESULTS: A total of 50 375 admissions were included in the analysis, 747 of whom developed significant UGIH. After adjusting for confounders, the adjusted odds ratio (aOR) of in-hospital mortality for patients who developed UGIH was 7.1 (95% confidence interval: 2.1-23.9, P<0.01) compared with those who did not. Significant UGIH was associated with substantial increase in morbidity [shock: aOR: 4.1 (2.1-9.3), P<0.01, prolonged mechanical ventilation: aOR: 5.8 (2.2-12.4), P<0.01, total parenteral nutrition: aOR: 4.7 (1.9-10.7), P<0.01], and resource utilization [mean adjusted difference in: length of hospital stay: 7.01 (4.72-9.29), P<0.01 and total hospitalization charges: $81 818 ($58 109-$105 527), P<0.01 and costs: $25 230 ($17 805-$32 653), P<0.01]. Similar results were obtained using multivariate regression analysis. CONCLUSION: Onset of significant UGIH among patients hospitalized with AC has a detrimental effect on in-hospital mortality, morbidity and resource utilization.

Evaluation of Biliary Bacterial Resistance in Patients with Frequent Biliary Instrumentation, One Size Does Not Fit All.

BACKGROUND: Bacteremia due to cholangitis can occur as a complication of biliary instrumentation. Biliary sepsis can result from frequent endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We hypothesized that routine use of antibiotics in patients who require frequent ERCPs leads to cholangitis resistant to empiric antibiotics used to treat biliary sepsis. We retrospectively reviewed patients with frequent biliary instrumentation and blood stream infection due to cholangitis. Conventional empiric antibiotics were defined as broad-spectrum antibacterial agents predominantly used for community-acquired infections and surgical prophylaxis. Broad-spectrum antibacterial agents used for hospital-onset/multidrug-resistant infections were defined as broad-spectrum MDR antibiotics. RESULTS: Seventy-eight patients had bacteremia secondary to cholangitis from biliary obstruction. Over 50% of bacteria were not sensitive to conventional empiric antibiotics for biliary sepsis. Thirty-seven patients did not receive post-procedural antibiotics and forty-one patients did. Of the ones who did, 58% later had a bloodstream infection with bacteria resistant to the antibiotic used for prophylaxis, and 26 patients (63%) required a broad-spectrum MDR antibiotic for treatment. The number of ERCPs was not associated with resistance to prophylactic antibiotics (p 0.7103) or needing broad-spectrum MDR antibiotics for treatment of cholangitis-associated bacteremia (p 0.1868). Routine use of antibiotic prophylaxis after ERCP was associated with trend toward need for broad-spectrum MDR antibiotics for cholangitis-associated bacteremia, Chi-square 3.7, 0 0.0540. CONCLUSION: Bacterial resistance to conventional empiric antibiotics is an emerging problem. Blood cultures are needed to guide therapy.

Red blood cell distribution width to platelet ratio levels in assessment of histologic severity in patients with primary biliary cholangitis.

We aimed to investigate the relationship between the histologic severity and red blood cell distribution width to platelet ratio (RPR) in patients with primary biliary cholangitis (PBC). One hundred and seven consecutive patients with liver biopsy-proven and as yet treatment-naïve PBC were enrolled as the primary and validation cohort. The histologic stages were divided into early stage (Scheuer's stage 1 & 2) and late stage (Scheuer's stage 3 & 4). The overall patient demographics, clinical manifestations, hematological tests and biochemical profile were retrospectively collected from our database. Both groups were compared in terms of RPR, aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4) and AST/ALT ratio (AAR). Of the 77 patients in the primary cohort, a total of 24 (31.2%) had early stage PBC, whereas 53 (68.8%) represented late stage. Patients with late stage PBC showed significantly higher red blood cell distribution width (15.5 vs. 14.1%, p = .016), RPR (0.15 vs. 0.09, p < .001), direct bilirubin (32.4 vs. 12.9 µmol/L, p = .041), FIB-4 (3.41 vs. 6.34, p = .001) and significantly lower platelet (132.8 vs. 185.8 × 109/L, p = .002). The area under the curve, cut-off value, sensitivity, specificity, positive predictive value, negative predictive value for determining late stage were 0.74, 0.14, 49.1%, 95.8%, 96.3% and 46.0%, respectively. Additionally, high RPR may also serve as a prognostic indicator for 18-month mortality. In conclusion, RPR can be used as a non-invasive and effective predictor of histologic severity in patients with PBC.

Outcomes Associated With Timing of ERCP in Acute Cholangitis Secondary to Choledocholithiasis.

GOALS: To determine the outcomes associated with timing of endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute cholangitis due to choledocholithiasis, from a population-based study. BACKGROUND: Although ERCP is the cornerstone in the management of patients with acute cholangitis due to choledocholithiasis, the effect of timing of ERCP on health care outcomes is not well known. MATERIALS AND METHODS: In this retrospective study, national inpatient sample (NIS) data were used to identify patients with a combined primary or secondary diagnosis of cholangitis and choledocholithiasis from 1998 to 2012. Patients were divided into 4 groups based on timing of ERCP after admission: (1) ERCP performed within 24 hours (urgent ERCP); (2) ERCP performed between 24 and 48 hours (early ERCP); (3) ERCP performed after 48 hours (delayed ERCP); and (4) no ERCP performed. Main outcomes measured were length of stay (LOS), hospitalization charges, and in-hospital mortality. RESULTS: A total of 107,253 patients were identified of which 77,323 patients underwent ERCP at any point in time. Urgent ERCP group had shortest LOS, while delayed ERCP group had significantly longer LOS than all other groups (P<0.001). Delayed ERCP group had also the highest costs (P<0.001). In-hospital mortality was highest in no ERCP group, followed by delayed ERCP group (P<0.001); there was no difference in mortality between urgent ERCP and early ERCP. CONCLUSIONS: This study provides robust, population-based evidence that ERCP should not be delayed for >48 hours in patients with acute cholangitis due to choledocholithiasis.

Current assessment of choledochoduodenostomy: 130 consecutive series.

Introduction Cholelithiasis usually can be managed successfully by endoscopic sphincterotomy. Choledochoduodenostomy (CDD) is one of the surgical treatment options but its acceptance remains debated because of the risk of reflux cholangitis and sump syndrome. The aim of this study was to assess the current features and outcomes of patient undergoing CDD. Patients and methods We retrospectively analysed the surgical results of consecutive 130 patients treated by CDD between 1991 and 2013 and excluded five cases with a malignant disorder. Indications for surgery included endoscopic management where stones were difficult or failed to pass and primary common bile duct stones with choledochal dilatation. Incidences of reflux cholangitis, stone recurrence, pancreatitis or sump syndrome were investigated and the data between end-to-side and side-to-side CDD were compared. Results Reflux cholangitis and stone recurrence was 1.6% (2/125) and 0% (0/125) of cases by CDD. There is no therapeutic-related pancreatitis in CDD. Sump syndrome was not also observed in side-to-side CDD. Conclusions This study is a first comparative study between end-to-side and side-to-side CDD. The surgical outcomes for CDD treatment of choledocholithiasis were acceptable. The incidence of reflux cholangitis, stone recurrence, pancreatitis and sump syndrome was very low.

Assessment of Pharmacokinetic Interactions Between Obeticholic Acid and Caffeine, Midazolam, Warfarin, Dextromethorphan, Omeprazole, Rosuvastatin, and Digoxin in Phase 1 Studies in Healthy Subjects.

INTRODUCTION: Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters. METHODS: Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin). RESULTS: OCA showed no substantial suppression/inhibition of S-warfarin, digoxin, and dextromethorphan and weak interactions with caffeine, omeprazole, rosuvastatin, and midazolam. The maximal pharmacodynamic responses (E max) to warfarin-based INR, PT, and aPTT were reduced by 11%, 11%, and 1%, respectively, for the 10-mg dose group and by 7%, 7% and 0%, respectively, for the 25-mg dose group. Overall, drugs dosed in combination with OCA were well tolerated, and most adverse events were mild in severity. No clinically important trends were noted in laboratory evaluations, vital signs, or 12-lead ECGs. CONCLUSION: In these studies, OCA showed weak to no suppression/inhibition of metabolic enzymes and drug transporters at the highest recommended therapeutic dose in patients with PBC. On the basis on these analyses, monitoring and maintenance of target INR range are required during coadministration of OCA with drugs that are metabolized by CYP1A2 (R-warfarin). FUNDING: Intercept Pharmaceuticals, Inc.

Magnetic resonance imaging and spectroscopy for differential assessment of liver abnormalities induced by Opisthorchis felineus in an animal model.

BACKGROUND: European liver fluke Opisthorchis felineus, causing opisthorchiasis disease, is widespread in Russia, Ukraine, Kazakhstan and sporadically detected in the EU countries. O. felineus infection leads to hepatobiliary pathological changes, cholangitis, fibrosis and, in severe cases, malignant transformation of bile ducts. Due to absence of specific symptoms, the infection is frequently neglected for a long period. The association of opisthorchiasis with almost incurable bile duct cancer and rising international migration of people that increases the risk of the parasitic etiology of liver fibrosis in non-endemic regions determine high demand for development of approaches to opisthorchiasis detection. METHODOLOGY/PRINCIPAL FINDINGS: In vivo magnetic resonance imaging and spectroscopy (MRI and MRS) were applied for differential assessment of hepatic abnormalities induced by O. felineus in an experimental animal model. Correlations of the MR-findings with the histological data as well as the data of the biochemical analysis of liver tissue were found. MRI provides valuable information about the severity of liver impairments induced by opisthorchiasis. An MR image of O. felineus infected liver has a characteristic pattern that differs from that of closely related liver fluke infections. 1H and 31P MRS in combination with biochemical analysis data showed that O. felineus infection disturbed hepatic metabolism of the host, which was accompanied by cholesterol accumulation in the liver. CONCLUSIONS: A non-invasive approach based on the magnetic resonance technique is very advantageous and may be successfully used not only for diagnosing and evaluating liver damage induced by O. felineus, but also for investigating metabolic changes arising in the infected organ. Since damages induced by the liver fluke take place in different liver lobes, MRI has the potential to overcome liver biopsy sampling variability that limits predictive validity of biopsy analysis for staging liver fluke-induced fibrosis.