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Haemobilia is an unusual but significant cause of upper gastrointestinal bleeding. Two-thirds of haemobilia cases are secondary to invasive hepato-biliopancreatic procedures. Biliary angiodysplasia is exceptionally unusual, with only three cases reported. Herein, we report the case of an autonomous 80-year-old woman with a history of cholecystectomy 5 years ago and cardiovascular disease—hypertension, heart failure, acute myocardial infarction, stroke and non-valvular atrial fibrillation, anticoagulated with apixaban 2.5 mg two times per day. Since July 2019, she had four episodes of acute cholangitis of mild-to-moderate severity, having undergone broad spectrum antibiotics treatment and endoscopic retrograde cholangiopancreatography (ERCP), with sphincterotomy and bile sludge extraction. After 3 months, the patient presented with a new episode of acute cholangitis, this time with haemobilia (Quincke’s triad). An abdominal CT angiography showed no evidence of active bleeding, with plastic biliary prosthesis left by ERCP. The patient continued presenting new episodes of acute cholangitis with haemobilia, some of them with associated pancreatitis. A cholangioscopy with Spyglass DS II was performed, showing an angiodysplasia occupying half of the luminal circumference of the middle choledoccus, without active haemorrhage. After a multidisciplinary meeting and given the high haemorrhagic/thrombotic risk (CHA2DS2-VASc 8), closure of the left atrial appendage was considered. However, relapse of the condition after beginning the antiaggregation protocol for cardiovascular intervention made it unfeasible. Another cholangioscopy with an ultra-thin endoscope for argon-plasma coagulation was attempted, without success. The abdominal CT angiography was repeated, this time with identification of dilated ramifications of the gastroduodenal and inferior pancreatic arteries. After embolisation of these aberrant vessels with microcoils, the patient went well, with no recurrence of bleeding or biliopancreatic complications. We present a case of obstructive haemobilia with multiple biliopancreatic complications, secondary to an extremely rare cause—choledochal angiodysplasia. Cholangioscopy had a decisive role in the diagnosis and therapeutic guidance. The diagnostic/therapeutic challenge associated with haemobilia stands out, with the need for a personalised and multidisciplinary approach.

Hepatic artery pseudoaneurysm (HAP) is mostly encountered secondary to trauma or iatrogenic causes. HAP associated with cholangitic liver abscess is a rare complication. We present a case of gallstone disease and choledocholithiasis who developed moderate cholangitis and a liver abscess. A small HAP was detected incidentally on a biphasic CT done to evaluate the biliary system. Repeat CT after management with endoscopic retrograde cholangiopancreatography and antibiotics showed resolution of cholangitic abscess with spontaneous thrombosis of HAP.

Kasai portoenterostomy (KPE) is the standard surgical management for biliary atresia (BA). To improve the outcome these infants were operated on within the first two months of life. The success of the procedure is reflected by clearance of jaundice and either absence or occurrence of fewer attacks of cholangitis. The failure of the procedure indicates liver transplantation (LT).to reduce the incidence of the recurrent attacks of cholangitis by peri-KPE sutures anchoring the jejunal loop to the Glisson capsule.It is a retrospective study that included 45 infants diagnosed with BA and who were operated on at an age younger than 60 days. They were categorized into two groups, Group A (n = 23) included infants treated with the classic KPE, and Group B (n = 22) included infants treated in the same way plus peri KPE sutures anchoring the jejunal loop to the Glisson capsule.The mean operative time in Group A was 149.3 min versus 164.8 min in Group B (p-value 0.039). The mean level of bilirubin was 2.2 versus 2.1 in Group A and Group B respectively at two years follow up. The total attacks of cholangitis per patient were significantly lower in Group B than in Group A (cutoff value = 3), which was reflected by the significant reduction of the incidence of LT in Group B.peri KPE sutures anchoring the jejunal loop to the Glisson capsule significantly reduced the incidence of recurrent attacks of cholangitis and subsequently decreased the requirement of LT on the short-term follow-up.

An 89-year-old man with polycystic liver disease (PCLD) received uncovered self-expandable metallic stent (SEMS) placement above the papilla for malignant biliary obstruction caused by cholangiocarcinoma. He developed cholangitis ten months later due to SEMS occlusion caused by tumor ingrowth, and 2 plastic biliary stents were placed inside the SEMS across the papilla. Fever and right costal pain appeared two weeks after reintervention. Suspecting hepatic cyst infection based on imaging studies, percutaneous transhepatic cyst drainage was performed. Increased inflammatory cells and the presence of pathogens in the cyst fluid led to a definitive diagnosis of hepatic cyst infection. Following drainage, the hepatic cyst shrank with resolution of the symptoms. SEMS occlusive-related cholangitis or retrograde infection due to duodenal-biliary reflux after reintervention was considered as the cause of the hepatic cyst infection. Careful clinical and imaging evaluation should be performed in patients with PCLD undergone biliary stenting, because cyst infection may occur following stent occlusion or subsequent biliary reintervention.

Primary biliary cholangitis (PBC) is an autoimmune liver disease with a female predisposition and selective destruction of intrahepatic small bile ducts leading to nonsuppurative destructive cholangitis. It is characterized by seropositivity of antimitochondrial antibodies or PBC-specific antinuclear antibodies, progressive cholestasis, and typical liver histologic manifestations. Destruction of the protective bicarbonate-rich umbrella is attributed to the decreased expression of membrane transporters in biliary epithelial cells (BECs), leading to the accumulation of hydrophobic bile acids and sensitizing BECs to apoptosis. A recent X-wide association study reveals a novel risk locus on the X chromosome, which reiterates the importance of Treg cells.

Primary biliary cholangitis (PBC) is a chronic immune-mediated liver disease characterized by a lymphocytic cholangitis, with subsequent cholestasis, progressive liver fibrosis, and ultimately complications arising from end-stage liver disease. Testing for autoantibodies is important in the diagnosis of PBC, as well as stratifying prognosis. This review focuses on the role of autoantibodies in the diagnosis of PBC, as well as the relationship between autoantibodies with pathophysiology and prognostication, along with a discussion regarding novel and other related disease autoantibodies.

The optimal timing for endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis (AC) has not been unequivocally established.To perform a meta-analysis of the outcomes associated with particular timings of ERCP for AC.A systematic literature search was conducted for studies of ERCP for AC, and then a meta-analysis of the in-hospital mortality (IHM), 30-day mortality, and length of hospital stay (LHS) was performed.Seven non-randomized studies of 88,562 patients were considered appropriate for inclusion. Compared with performing ERCP more than 24 hours after admission, ERCP within 24 hours was associated with lower IHM ( P0.0004), but no difference in 30-day mortality ( P =0.38) was found between the 2 groups. ERCP performed48 hours after admission was associated with a lower IHM and 30-day mortality ( P0.00001 and P =0.03) than ERCP performed48 hours after admission. In addition, ERCP performed within 24 or 48 hours was associated with a shorter LHS ( P0.00001 and P0.00001, respectively).ERCP within 48 hours of admission is superior to subsequent ERCP with respect to IHM, 30-day mortality, and LHS, and ERCP performed within 24 hours is associated with lower IHM and LHS.

Acute cholecystitis can occur both inside and outside hospital settings. However, little is known about the clinical characteristics of hospital-acquired cholecystitis (HAC).To investigate the clinical characteristics of HAC in a tertiary academic hospital.This retrospective cohort study included hospitalized patients who were found to have gallstones without cholecystitis or cholangitis on admission between January 2018 and December 2021. Multi-variate logistic regression analysis was used to make comparisons between patients with and without HAC.In total, 890 patients met the inclusion criteria and were evaluated in this study. Forty-one patients (4.6%) developed HAC during the study period. Multi-variate logistic regression analysis showed that a history of cholecystitis or cholangitis, fasting for ≥1 day, and gallstones in the gallbladder neck were independently associated with increased risk of HAC. HAC occurred most frequently after several weeks of admission, and only four patients (9.8%) had bacteraemia.HAC was relatively common among hospitalized patients. Physicians should be aware of the possibility of HAC in symptomatic hospitalized patients with certain risk factors.

Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune liver disease that can progress to end-stage liver disease and its complications. A previous expert review panel collaborated on a consensus document for gastroenterologists and other healthcare professionals regarding the care of patients with PBC. Subsequently, there have been several recent important developments in the diagnosis, treatment, and monitoring of patients with PBC. These include updates to prognostic models on risk stratification, new noninvasive tools for staging of disease, updates to the appropriate use of and long-term treatment results with obeticholic acid as a second-line treatment, the emerging therapeutic role of fibrates, and the advancement of investigational agents for managing PBC. In this updated expert consensus document, we provide updates on staging, the use of noninvasive prognostic tools, and a treatment algorithm to provide evidence-based and practical tools for clinicians who manage PBC, with the ultimate goal to improve the long-term outcomes for patients with this chronic liver disease.

Purpose Hepatobiliary scintigraphy is a minimally invasive imaging method that evaluates bile flow dynamics. At our hospital, it has been performed for postoperative evaluation of patients with choledochal cysts (CC). This study evaluated the usefulness of biliary scintigraphy for predicting late complications in patients with CCs. Methods The study included pediatric patients with CC who underwent surgery at Chiba University Hospital from 1978 to 2020, followed by postoperative biliary scintigraphy and subsequent radiologic evaluation. The patients were divided into two groups according to the presence or absence of “biliary cholestasis” on biliary scintigraphy. Results The study included 108 patients, with a median age at surgery of 2 years and 11 months. The median follow-up period was 5203 days, with 11 hepatolithiasis cases and 8 cholangitis cases. No patients had cholangiocarcinoma. Twelve patients were considered to have “cholestasis” following biliary scintigraphy evaluation. There was no significant difference in the occurrence of hepatolithiasis between the cholestasis and non-cholestasis groups (p = 0.47), but cholangitis was significantly more common in the cholestasis group (p = 0.016). Conclusion Biliary cholestasis on postoperative hepatobiliary scintigraphy was a risk factor for cholangitis in patients with CCs. These particular patients should be monitored carefully.

On 20 October 2020, an 88-year-old man presented with a 12-hour history of right upper abdominal pain, nausea and vomiting. His medical history included that of iliopsoas and epidural abscesses 3 years before presentation, which made him bedridden. Physical examination revealed body temperature of

BackgroundPrimary sclerosing cholangitis (PSC) is frequently associated with pruritus, which significantly impairs quality of life. Maralixibat is a selective ileal bile acid transporter (IBAT) inhibitor that lowers circulating bile acid (BA) levels and reduces pruritus in cholestatic liver diseases. This is the first proof-of-concept study of IBAT inhibition in PSC.MethodsThis open-label study evaluated the safety and tolerability of maralixibat ≤10mg/d for 14 weeks in adults with PSC. Measures of pruritus, biomarkers of BA synthesis, cholestasis, and liver function were also assessed.ResultsOf 27 enrolled participants, 85.2% completed treatment. Gastrointestinal treatment-emergent adverse events (TEAEs) occurred in 81.5%, with diarrhea in 51.9%. TEAEs were mostly mild or moderate (63.0%); 1 serious TEAE (cholangitis) was considered treatment related. Mean serum BA (sBA) levels decreased by 16.7% (-14.84µmol/L; 95% CI, -27.25 to -2.43; p = 0.0043) by week 14/early termination (ET). In participants with baseline sBA levels above normal (n = 18), mean sBA decreased by 40.0% (-22.3µmol/L, 95% CI, -40.38 to -4.3; p = 0.004) by week 14/ET. Liver enzyme elevations were not significant; however, increases of unknown clinical significance in conjugated bilirubin levels were observed. ItchRO weekly sum scores decreased from baseline to week 14/ET by 8.4% (p = 0.0495), by 12.6% (p = 0.0275) in 18 participants with pruritus at baseline, and by 70% (p = 0.0078) in 8 participants with ItchRO daily average score ≥3 at baseline.ConclusionsMaralixibat was associated with reduced sBA levels in adults with PSC. In participants with more severe baseline pruritus, pruritus improved significantly from baseline. TEAEs were mostly gastrointestinal related. These results support further investigation of IBAT inhibitors for adults with PSC-associated pruritus. ClinicalTrials.gov: NCT02061540.

Introduction: Patients with inflammatory bowel diseases (IBDs) of the colon are at an increased risk of colorectal cancer (CRC). This study investigates the epidemiology of IBD-CRC and its outcomes. Methods: Using population data from the English National Health Service held in the CRC data repository, all CRCs with and without prior diagnosis of IBD (Crohn's, ulcerative colitis, IBD unclassified, and IBD with cholangitis) between 2005 and 2018 were identified. Descriptive analyses and logistic regression models were used to compare the characteristics of the 2 groups and their outcomes up to 2 years. Results: Three hundred ninety thousand six hundred fourteen patients diagnosed with CRC were included, of whom 5,141 (1.3%) also had a previous diagnosis of IBD. IBD-CRC cases were younger (median age at CRC diagnosis [interquartile range] 66 [54–76] vs 72 [63–79] years [P < 0.01]), more likely to be diagnosed with CRC as an emergency (25.1% vs 16.7% [P < 0.01]), and more likely to have a right-sided colonic tumor (37.4% vs 31.5% [P < 0.01]). Total colectomy was performed in 36.3% of those with IBD (15.4% of Crohn's, 44.1% of ulcerative colitis, 44.5% of IBD unclassified, and 67.7% of IBD with cholangitis). Synchronous (3.2% vs 1.6% P < 0.01) and metachronous tumors (1.7% vs 0.9% P < 0.01) occurred twice as frequently in patients with IBD compared with those without IBD. Stage-specific survival up to 2 years was worse for IBD-associated cancers. Conclusion: IBD-associated CRCs occur in younger patients and have worse outcomes than sporadic CRCs. There is an urgent need to find reasons for these differences to inform screening, surveillance, and treatment strategies for CRC and its precursors in this high-risk group.

Patients with malignant hilar biliary strictures can suffer from obstructive jaundice. Controversy remains on the optimal approach to obtain preoperative or palliative biliary drainage in these patients. A systematic review and meta-analysis was conducted to compare the two modalities most commonly used in this scenario: endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC).MEDLINE via PubMed was searched for relevant articles published from 2005 to April 2019. Following outcome measures were used to compare ERCP and PTC: therapeutic success rate, cholangitis, pancreatitis, bleeding, tube dislocation, reintervention rate, mortality such as 30d mortality and in-hospital death, median survival time, drainage patency, duration until decompression and hospital stay. Risk of bias assessment for the retrospective studies was conducted by NOS. RoB 2 was used for RCT. A meta-analysis was performed by using Review Manager 5.3. The certainty of evidence was appraised using GRADE.Eleven articles of which one RCT and ten retrospective cohort studies fulfilled the inclusion criteria for data-analysis (1417 patients; 784 ERCP, 633 PTC). The combined odds ratio (OR) for therapeutic succes was 3.5 times higher in the PTC group (95% CI 2.05-5.97; high certainty). In terms of cholangitis, ERCP carried a 1.7-fold risk as compared to PTC (95% CI 0.92-3.08; moderate certainty). Patients who underwent ERCP were 11.50 times more likely to undergo a reintervention (95% CI 3.51-37.70; moderate certainty). ERCP was comparable to PTC in terms of pancreatitis (low certainty), bleeding (high certainty) and tube dislocation rate (moderate certainty). Mortality tended to be numerically higher in the PTC group but low patient numbers, selection bias and study heterogeneity did not allow uniform comparative analysis.In patients with malignant hilar biliary strictures, PTC is associated with a better therapeutic success rate, less cholangitis and lower reintervention rate as compared to ERCP.

Biliary decompression is well known to greatly decrease the risks of mortality in acute cholangitis (AC). Although early biliary drainage is recommended by the treatment guidelines for AC, the best time for performing this procedure is yet to be established. Furthermore, since the clinical outcomes of patients with severe AC vary dramatically, screening for patients that could benefit the most from early drainage would be more beneficial than the drainage performed based on the severity grade criteria.To investigate the optimal drainage timing for AC patients with each disease severity grade and organ dysfunction.In this retrospective monocenter cohort analysis, we reviewed 1305 patients who were diagnosed with AC according to the Tokyo guidelines 2018 at a Chinese tertiary hospital between July 2016 and December 2020. Demographic characteristics including age and sex, clinical and laboratory characteristics, and imaging findings of each patient were obtained from electronic medical records. We investigated the all-cause in-hospital mortality (IHM), hospital length of stay (LOS), and hospitalization costs associated with the timing of biliary drainage according to the severity grading and different dysfunctioning organs and predictors [age, white blood cell (WBC) count, total bilirubin, albumin, lactate, malignant obstruction, and Charlton comorbidity index (CCI)].Biliary drainage within 24 or 48 h in Grade III AC patients could dramatically decrease IHM (3.9%Biliary drainage within 12 h is beneficial for AC patients with neurological or cardiovascular dysfunction, while complete biliary decompression within 24 h of admission is recommended for treating patients with Grade III AC.

Background Whether the anti-gp210 antibody can be used as a biomarker in patients with primary biliary cholangitis (PBC) remains controversial. Aims We aimed to investigate the association between anti-gp210 antibodies and prognosis in ursodeoxycholic acid (UDCA)-treated PBC patients. Methods We conducted a retrospective cohort study of 180 UDCA-treated PBC patients to assess the prognostic value of anti-gp210 antibodies using the Kaplan–Meier method and Cox proportional hazard regression analysis. Results Of the patients included in our analysis, 50 (27.8%) were anti-gp210 positive, and 130 (72.2%) were anti-gp210 negative. The incidence of liver-related death or transplantation was more common in the anti-gp210 + group (22.0 vs. 9.2%, P=0.022). The five-year transplant-free survival rates of anti-gp210-positive patients vs. anti-gp210-negative patients were 77.0% and 90.3%, respectively. We found that the probability of transplant-free survival was significantly lower in the anti-gp210-positive patients than in the anti-gp210-negative patients (log-rank P=0.004). After adjusting for potential confounders using multivariable Cox regression model, positivity for anti-gp210 antibody (hazard ratio: 4.619, 95% confidence interval: 1.895–11.261, P=0.001) was found to be independently associated with an increase in liver-related mortality or transplantation. Conclusion In this cohort of UDCA-treated PBC patients, positivity for anti-gp210 antibody was independently associated with a higher risk of liver-related death or transplantation.

Lipocalin2 (LCN2) is being increasingly used to diagnose and predict severe bacterial infection. We aimed to evaluate the predictive value of serum lipocalin 2 for severity grading of acute cholangitis (AC) on patient admission.A total of 108 patients were enrolled in this study. Blood samples were obtained at admission. Receiver operating characteristic (ROC) curves were built to assess the abilities of LCN2 levels to predict moderate/severe (vs. mild) or severe (vs. mild/moderate) AC with traditional markers of inflammation such as white blood cell (WBC) count, C-reactive protein (CRP), procalcitonin (PCT) and neutrophil-to-lymphocyte ratio (NLR). The correlations among the key research indicators were determined using spearman's test. Multivariate analysis was conducted to identify the risk factors for severe AC.The levels of LCN2 on admission increased significantly with the severity of AC. By analysis of ROC curve of biomarkers for differentiating patients with moderate to severe AC (versus mild AC), the AUC for LCN2 (0.925) was significantly greater than that for other inflammatory markers, and the optimal cut-off value of LCN2 was 262.2 ng/mL, with a sensitivity of 90.8% and specificity of 81.4%. In addition, the AUC for LCN2 (0.912) for severe acute cholangitis was also significantly greater than that for other inflammatory markers, and the optimal cut-off value of LCN2 was 325.7 ng/mL. The sensitivity and specificity were 86.1% and 83.3%, respectively. Furthermore, LCN2 the closest relationships were found between LCN2 and PCT (r = 0.8054, P 0.001) through Spearman's test. Multivariate analysis showed that LCN2 was the only risk factor predicting severe AC (P 0.05).Serum LCN2 concentration on patient admission could better predict severe acute cholangitis than WBC, CRP, PCT and NLR. Serum LCN2 may become a potential biomarker in the risk stratification of acute cholangitis and in indicating the time of biliary drainage.

Purpose Laparoscopic duodenum–preserving pancreatic head resection (L-DPPHR) is technically demanding with extreme difficulty in biliary preservation. Only a few reports of L-DPPHR are available with alarming bile leakage, and none of them revealed the long-term metabolic outcomes. For the first time, our study explored the different dosage and timing of indocyanine green (ICG) for guiding L-DPPHR and described the long-term metabolic results. Methods Between October 2015 and January 2021, different dosage and timing of ICG were administrated preoperatively and evaluated intra-operatively using Image J software to calculate the relative fluorescence intensity ratio of signal-to-noise contrast between bile duct and pancreas. Short-term complications and long-term metabolic disorder were collected in a prospectively maintained database and analyzed retrospectively. Results Twenty-five patients were enrolled without conversion to laparotomy or pancreaticoduodenectomy. Administrating a dosage of 0.5 mg/kg 24 h before the operation had the highest relative fluorescence intensity ratio of 19.3, and it proved to guide the biliary tract the best. Fifty-six percent of patients suffered from postoperative complications with 48% experiencing pancreatic fistula and 4% having bile leakage. No one suffered from the duodenal necrosis, and there was no mortality. When compared with the non-ICG group, the ICG group had a comparable diameter of tumor and similar safety distance from lesions to common bile duct; however, it decreased the incidence of bile leakage from 10% to none. The median length of hospital stay was 16 days. After a median follow-up of 26.6 months, no one had tumor recurrence or refractory cholangitis. No postoperative new onset of diabetes mellitus (pNODM) was observed, while pancreatic exocrine insufficiency (pPEI) and non-alcoholic fatty liver disease (NAFLD) were seen in 4% of patients 12 months after the L-DPPHR. Conclusion L-DPPHR is feasible and safe in selected patients, and real-time ICG imaging with proper dosage and timing may greatly facilitate the identification and the prevention of biliary injury. And it seemed to be oncological equivalent to PD with preservation of metabolic function without refractory cholangitis.

Bilateral hepatolithiasis is an intractable disease and repeated attacks of acute cholangitis seriously threaten patient health. The surgical approaches evolve along with gradually greater understanding of its pathophysiology.This is a retrospective cohort study for bilateral hepatolithiasis from January 1958 to December 2018. Before May 1993 (Group A, n = 70), three surgical approaches were adopted: 37 patients with common bile duct exploration (CBDE), 29 with choledochoenterostomy (CE) and four with partial hepatectomy (PH). After June 1993 (Group B, n = 150), 101 patients underwent Oddi sphincter-preserved cholangioplasty with hepatico-subcutaneous stoma (OSPCHS), and 16 with CBDE, 21 with CE, 12 with PH. The perioperative and long-term outcomes were compared.After 1993, the cholangitis recurrence rate significantly decreased from 49.2% to 20.9%, and the stone recurrence rate from 76.3% to 37.1% (both P .001). Also, the stone-/cholangitis-free durations were prolonged significantly (median: 50.8 vs 26.4/49.6 vs 16.2 months, both P .001). Preoperative cholangitis was an independent risk factor for stone recurrence (hazard ratio [HR] = 1.863, P = .018), and residual stone for cholangitis recurrence (HR = 2.838, P .001). OSPCHS and PH were protective surgical approaches for recurrent stone (CBDE: reference; OSPCHS: HR = .469, P = .016, PH: HR = .219, P = .018) and cholangitis (CBDE: reference; OSPCHS: HR = .421, P = .010, PH: HR = .283, P = .093).For bilateral hepatolithiasis, the management should focus on hepatobiliary lesion eradication and Oddi sphincter function preservation.

Cholangitis has been reported as an immune-related adverse event, although it rarely occurs. Here we report a case of cholangitis due to atezolizumab in a 77-year-old woman who had been treated with atezolizumab and nab-paclitaxel for breast cancer and lung metastasis. On the seventh cycle, she presented with fever and epigastric pain, and computed tomography and endoscopic ultrasound showed slight wall thickening of the common bile duct, and transpapillary bile duct biopsy was performed. Pathologically, CD8

Background. Infection in acute pancreatitis will worsen the disease prognosis. The aim of our study was to analyze the role of procalcitonin as a prognostic biomarker for infections and clinical severity. Method. A prospective single-cohort observational study of patients diagnosed of acute pancreatitis (n = 152) was designed. PCT determination was tested on admission (first 72 hours). Infections (biliary, extrapancreatic and infected pancreatic necrosis), need for antibiotics, need for urgent ERCP and severity scores for acute pancreatitis was assessed. ROC curves were designed and the area under the curve was calculated. Logistic regression for multivariate analysis was performed to evaluate the association between procalcitonin optimal cut-off level and major complications. Results. PCT > 0.68mg/dL had higher incidence of global infection, acute cholangitis, bacteraemia, infected pancreatic necrosis, use of antibiotics in general, and need for urgent ERCP. In the multivariate regressions analysis, PCT > 0.68mg/dL at admission demonstrated to be a strong risk factor for complications in acute pancreatitis. Discussion. PCT levels can be used as a reliable laboratory test to predict infections and the clinical severity of acute pancreatitis. High levels of PCT predict antibiotics prescription as well as the need for urgent ERCP in patients with concomitant clinically severe cholangitis.

Background: Acute cholangitis (AC) is a gastro-intestinal emergency associated with significant mortality. Role of change in the levels of inflammatory markers post drainage in predicting outcome in acute cholangitis is uncertain. Objective: To evaluate the predictive value of changes in C-reactive protein (CRP) and procalcitonin levels after biliary drainage in relation to outcomes (survival or mortality) at 1 month. Methods A prospective observational study of consecutive adults presenting with AC was performed. At admission and at 48 hours post biliary drainage, procalcitonin and CRP were sent. Results: Between August 2020 till December 2020 we recruited 72 consecutive patients of AC. The median age of the patients was 55 years (range 43-62 years) and 42 (58.33%) were females. Although the delta change in serum procalcitonin (P value

Purpose:Impacted common bile duct stones cause severe acute cholangitis. However, the early and accurate diagnosis, especially iso-attenuating stone impaction, is still challenging. Therefore, we proposed and validated the bile duct penetrating duodenal wall sign (BPDS), which shows the common bile duct penetrating the duodenal wall on coronal reformatted computed tomography (CT), as a novel sign of stone impaction., Results:A total of 40 patients (mean age 70.6 years; 18 female) were enrolled. The BPDS was observed in 15 patients. Stone impaction occurred in 13/40 (32.5%) cases. Overall accuracy, sensitivity, and specificity were 34/40 (85.0%), 11/13 (84.6%), and 23/27 (85.2%), respectively; 14/16 (87.5%), 5/6 (83.3%), and 9/10 (90.0%) for iso-attenuating stones; and 20/24 (83.3%), 6/7 (85.7%), and 14/17 (82.4%) for high-attenuating stones. Interobserver agreement of the BPDS was substantial (κ = 0.68). In addition, the BPDS was significantly correlated with the number of factors in the systemic inflammatory response syndrome (P = 0.03) and total bilirubin (P = 0.04)., Conclusion:The BPDS was a unique CT imaging finding to identify common bile duct stone impaction regardless of stone attenuation with high accuracy.

Clinical trials have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may be associated with a higher risk of biliary-related diseases in patients with type 2 diabetes. Limited real-world studies have examined the comparative biliary safety of GLP-1RAs versus other antihyperglycemic drugs. We aimed to estimate the comparative risk of biliary-related diseases between GLP-1RAs and sodium glucose cotransporter 2 inhibitors (SGLT2is), which are indicated for patients with similar diabetes severity in Taiwan.Retrospective cohort study.Taiwan National Health Insurance Database during 2011 to 2018.Patients with type 2 diabetes who initiated GLP-1RAs or SGLT2is.GLP-1RAs versus SGLT2is.We used an on-treatment approach to examine the effect of continuous use and an intention-to-treat approach to assess the effect of initiation of GLP-1RAs versus SGLT2is. We used Coxregression models to estimate the hazard ratios (HRs) and 95% confidenceintervals (CIs) for the composite hospitalized biliary-related diseases, including acute cholecystitis or cholecystectomy, choledocholithiasis, and acute cholangitis, after matching each GLP-1RA initiator to up to 10 SGLT2iinitiators using propensity scores (PSs). Among 78,253 PS-matched patients, GLP-1RA use was associated with a numerically higher risk of biliary-related diseases versus SGLT2i use in the on-treatment analysis, with an HR of 1.20 (95% CI, 0.93-1.56) for the composite outcome, an HR of 1.22 (95% CI, 0.92-1.62) for acute cholecystitis or cholecystectomy, an HR of 1.20 (95% CI, 0.69-2.07) for choledocholithiasis, and an HR of 1.14 (95% CI,0.82-2.42) for acute cholangitis. The HRs were more pronounced in theintention-to-treat analysis (1.27 [95% CI, 1.05-1.53] for the composite outcome, 1.29 [95% CI, 1.04-1.58] foracute cholecystitis or cholecystectomy, 1.74 [95% CI, 1.23-2.46] for choledocholithiasis, and 1.31 [95% CI, 0.89-1.94] for acute cholangitis). The increased risk of the composite outcome associated with GLP-1RAs was more evident in patients aged 〉60 years, women, and 120 days after treatment initiation. Liraglutide, but not dulaglutide, was associated with an elevated risk.GLP-1RAs might be associated with an elevated risk of biliary-related diseases compared to SGLT2is in Asian patients with type 2 diabetes.

The safety and feasibility of primary closure after laparoscopic common bile duct exploration (LCBDE) have been confirmed in elective settings. However, the suitability of primary closure after LCBDE in the treatment of patients with non-severe acute cholangitis in emergency settings remains unclear. The aim of the present study was to explore the safety and feasibility of LCBDE with primary closure in patients with non-severe acute cholangitis.Consecutive patients with choledocholithiasis combined with gallbladder stones treated by LCBDE with primary closure at our institution from January 2015 to April 2021 were retrospectively reviewed. These patients were divided into two groups: emergency group (patients with non-severe acute cholangitis) and elective group (patients without acute cholangitis). The demographic and perioperative data of the two groups were compared.One hundred twenty-two patients received LCBDE combined with primary closure during this period, including 70 in the emergency group and 52 in the elective group. Baseline characteristics were balanced in both groups, except for higher levels of white blood cells (WBC), C-reactive protein (CRP), total bilirubin, alkaline phosphatase (ALP), and albumin in the emergency group. No postoperative mortality occurred in either group. Compared to the elective group, the emergency group had a longer operation time (P = 0.011), and more estimated blood loss (P 0.001). No significant differences were found between the two groups in terms of conversion (2.9% vs. 0.0%, P = 0.507), use of baskets (84.2% vs. 78.8%, P = 0.481), use of electrohydraulic lithotripsy (EHL) (2.9% vs. 1.9%, P = 1.000), or postoperative hospital stay (P = 0.214). The incidence of postoperative complications was comparable between the two groups. During the follow-up period, none of the patients experienced biliary stricture, and 1 case of stone recurrence occurred in the elective group.LCBDE with primary closure for choledocholithiasis patients with non-severe acute cholangitis has the equivalent efficacy and morbidity to elective surgery. Primary closure after LCBDE is a safe and feasible option for choledocholithiasis patients with non-severe acute cholangitis.

Impaction of a stone at the duodenal papilla can obstruct biliopancreatic outflow and thereby lead to acute pancreatitis. But not all patients with an impacted papillary stone (IPS) had the clinical features of pancreatitis. This study aimed to identify factors associated with acute pancreatitis in patients with IPS.We retrospectively analyzed patients with IPS who underwent endoscopic retrograde cholangiopancreatography (ERCP) at Tianjin Nankai Hospital. Clinical factors were compared between patients with/without acute pancreatitis before ERCP. Factors associated with acute pancreatitis were identified by univariable and multivariable binary logistic regression.The final analysis included 174 patients with acute pancreatitis (pancreatitis group, PG) and 130 patients without acute pancreatitis (non-pancreatitis group, NPG). Preoperative incidences of jaundice (85.6 vs. 72.3%), acute cholangitis (54.6 vs. 33.8%), and hyperlipidemia (39.1 vs. 22.3%) were higher in the PG than in the NPG (Jaundice, acute cholangitis, and hyperlipidemia are independent risk factors for acute pancreatitis in patients with IPS. Prompt ERCP in patients with these features might reduce acute pancreatitis risk. Dot/circular papillary orifice may be an anatomical factor of acute pancreatitis, which needs more evidence.

We investigated associations between ethnicity, survival, and disease severity in a diverse Canadian cohort of patients with primary biliary cholangitis (PBC).Patients with PBC were included from the Canadian Network for Autoimmune Liver Disease. Ethnicity was defined using a modified list adopted from Statistics Canada, and ethnicities with small samples were grouped. Clinical events were defined as liver decompensation, HCC, liver transplantation, or death. Clinical event-free and liver transplantation-free survival were analyzed using Cox regression. Trajectories of serum liver function tests were assessed over time using mixed-effects regression. Health-related quality of life was assessed using the Short Form 36, the PBC-40 questionnaire, and the 5-D Itch scale and analyzed using mixed-effects regression. The cohort included 1538 patients with PBC from six sites and was comprised of 82% White, 4.7% Indigenous, 5.5% East Asian, 2.6% South Asian, and 5.1% miscellaneous ethnicities. Indigenous patients were the only ethnic group with impaired liver transplant-free and event-free survival compared to White patients (HR, 3.66; 95% CI, 2.23-6.01; HR, 3.09; 95% CI, 1.94-4.92). Indigenous patients were more likely to have a clinical event before diagnosis (10%) than all other ethnic groups despite similar age at diagnosis. Indigenous patients presented with higher alkaline phosphatase, total bilirubin, and GLOBE scores than White patients; and these relative elevations persisted during follow-up.Indigenous Canadians with PBC present with advanced disease and have worse long-term outcomes compared to White patients.

Treatment of primary biliary cholangitis (PBC) with ursodeoxycholic acid (UDCA) is not always sufficient to prevent progression to hepatic decompensation and/or need for liver transplant. Adjuvant therapy with obeticholic acid may provide additional biochemical improvements in some patients, but it is not well-tolerated by patients with significant itch or advanced cirrhosis. Thus, new and creative approaches to treating patients with PBC are important to identify. This review discusses major potential therapeutic targets in PBC and provides examples of some specific agents currently in development for the treatment of PBC. Targets are broadly classified into those which strive to modify bile, inflammation, cell survival, or fibrosis. In bile, shrinking the size of the bile acid pool or modifying the quality of the bile by making it more hydrophilic or enriched in phosphatidylcholine may ameliorate cholestatic injury. Biliary epithelial cell survival may be extended by fortifying the bicarbonate umbrella or improving cell membrane integrity. Autoimmunity and cholangitis have the potential to be improved via regulation of the immune system. Targeting cytokines, immune checkpoints, and anti-mitochondrial antibodies are examples of a more focused immunosuppression approach. Stem cell therapy and lymphocyte trafficking inhibition are more novel methods of broad immune regulation. Anti-fibrotic therapies are also potentially useful for preventing progression of PBC. The nuclear hormone receptors, farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) regulate many of these pathways: cholestasis, inflammation, and fibrosis, which is why they are being enthusiastically pursued as potential therapeutic targets in PBC.

Background The cornerstone of treatment for acute cholangitis is source control with biliary drainage and early antibiotics. The primary aim of this study was to describe the microbiology of bile aspirate pathogens obtained at the time of endoscopic retrograde cholangiopancreatography (ERCP) in patients suspected of having acute cholangitis. Methods In this single-center retrospective study, patients were included if a bile aspirate was collected at ERCP for suspicion of acute cholangitis, from 1 January 2010 to 31 December 2016. Results There were 721 ERCP procedures for suspected acute cholangitis with bile culture results, with 662 positive bile cultures (91.8 %). Pathogens included: Enterococcus species (spp.) 448 (67.7 %); Klebsiella spp. 295 (44.6 %); Escherichia coli 269 (40.6 %); Pseudomonas spp. 52 (7.9 %); and anaerobes 64 (9.7 %). Susceptibility of Klebsiella pneumoniae and E.coli isolates to ciprofloxacin was 88 % and 64 %, respectively. Extended-spectrum beta-lactamases and carbapenem resistance were found in 7.9 % and 3.6 % of Enterobacteriaceae, respectively. There were 437 concurrent blood cultures, of which 174 were positive (39.8 % of cultures drawn). Prior biliary endoscopic sphincterotomy (ES) was evident in 459 ERCP cases (63.7 %), and was associated with increased frequency of Klebsiella spp., Pseudomonas aeruginosa, Enterobacter spp., and Enterococcus spp. Prior biliary ES significantly increased the probability of vancomycin-resistant Enterococcus (VRE). Conclusions The vast majority of bile cultures (91.8 %) were positive. The susceptibilities of E.coli and K.pneumoniae to ciprofloxacin are lower than historically noted. A notable portion of cultures contained pathogenic drug-resistant organisms. Prior biliary ES is associated with a higher frequency of certain organisms and higher frequency of VRE.

Open portoenterostomy (PE) for biliary atresia (BA) is currently more extended (EP) than the original (OP). Typical OP techniques, shallow transection of the biliary remnant and shallow suturing, both lost in EP, were revived as a modified procedure (MP). Postoperative outcomes of EP and MP were compared.Subjects were 55 consecutive BA patients treated by EP (n = 18) or MP (n = 37) at a single center between 2004 and 2021.Mean follow-up duration was: MP: 15.5 years (range 0.1-12.3 years) and EP: 15.5 years (range 0.38-17.1 years). The ratio of jaundice free (JF; total bilirubin ≤ 1.2 mg/dL) subjects was significantly higher in MP (78.4%) versus EP (50%); p 0.05, the incidence of bile lakes at the porta hepatis was significantly higher in MP (7/37: 18.9%) versus EP (0/18: 0%); p 0.05, and Kaplan-Meier analysis showed JF survival with the native liver (JF + SNL) was significantly better in MP (26/37: 70.2%) versus EP (4/18: 22.2%); p 0.05. All other criteria were similar. Of note, time taken to become JF and the incidence of cholangitis were not significantly different.Shallow transection and shallow suturing would appear to influence postoperative outcome. The etiology of bile lake formation in MP requires urgent confirmation.

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.We retrospectively assessed 251 patients with first episodes of acute cholangitis between January 2014 to September 2020.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.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.

Immune checkpoint inhibitors (ICIs) cause various immune-related adverse events (irAEs). We encountered a patient in whom nivolumab was re-administered effectively and safely treat laryngeal cancer after nivolumab-induced cholangitis. A 60-year-old man with metastatic laryngeal squamous cell carcinoma received 3rd-line treatment with nivolumab. After the 8th cycle of chemotherapy, laboratory tests revealed grade 3 elevations of gamma-glutamyl transpeptidase and alkaline phosphatase. Computed tomography and endoscopic retrograde cholangiopancreatography showed diffuse hypertrophy, dilation of bile ducts, and intrahepatic bile ducts with irregular walls and mild stenosis. The histologic findings of a liver biopsy revealed portal inflammation and cholangitis, mainly composed of T cell infiltration. We diagnosed nivolumab-induced cholangitis and administered 30 mg of prednisolone (0.5 mg/kg) and ursodeoxycholic acid (600 mg) per day. Although we initiated 4th-line cytotoxic anticancer drug after the cholangitis improved, the laryngeal cancer progressed rapidly. Based on the improvement in hematologic parameters, radiologic imaging, and pathologic findings, we cautiously restarted nivolumab. During the 30 months after re-administration of nivolumab, the cholangitis did not recur and the disease was well-controlled.

Tokyo guidelines (TG13/18) are used for the severity assessment of acute cholangitis (AC). Lactate is a clinical marker of tissue hypoxia and disease severity, independent from blood pressure.The aim of this study is to investigate the relationship between blood lactate level and TG13/18 criteria in patients diagnosed with AC.One hundred fifteen patients with AC were included in this retrospective study. Demographic characteristics of the patients and laboratory data were scanned from their hospital medical records. According to TG13/18 guidelines, the patients were divided into 3 groups as mild (grade 1), moderate (grade 2), and severe (grade 3) AC.Sixty three (54.7%) of the patients were grade 1, 37 (32.1%) were grade 2, and 15 (13.0%) were grade 3. It was found that blood lactate level increased significantly from grade 1 to grade 3 (p 0.001). In logistic regression analysis, white blood cell (WBC) count, total bilirubin and blood lactate levels independently determined the patients to be grade 2 or 3 AC. When the blood lactate cut-off value was taken as 16.5 mg/dL, we diagnosed grade 2 or 3 AC with a sensitivity of 78.8% and a specificity of 75.7%. From among lactate, WBC, and C reactive protein, lactate showed the highest value regarding the area under the curve, which is an index for predicting grade III upon ROC analysis.The blood lactate level is associated with the severity of AC. In addition to TG13/18 guidelines, blood lactate level can be a useful biomarker in the severity grading of AC.

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).

Background : : There is a paucity of literature regarding the prevalence of Mirizzi syndrome (MS) in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for obstructive jaundice. We aimed to describe the clinical presentation; laboratory, imaging, and ERCP findings; and surgical management of patients with MS at our center. Methods : : A retrospective review was performed of the medical records of 3,852 consecutive patients who underwent ERCP between January 2010 to December 2019 at our center. Results : : MS was diagnosed in 84 (2.2%) of the patients who underwent ERCP, with 45 male and 39 female patients. Jaundice was the most common symptom (100%) followed by abdominal pain (91.6%). Leukocytosis and altered liver function tests were noted in all our patients. Although most of our patients had one or more pre-procedure imaging studies, MS was confirmed and subclassified based on cholangiographic and intraoperative findings. There were 11 post-cholecystectomy MS patients who opted for endoscopic therapy with repeated biliary stenting. Among the remaining 73 patients, 48 with type I and 21 with type II MS underwent open cholecystectomy, 4 with type III MS received cholecystectomy and choledochoduodenostomy, and another 4 patients with type II MS underwent subtotal cholecystectomy and choledochoplasty. Associated cystic duct abnormalities were noted in 20.2% of patients. Bile duct injuries occurred in 3 patients during an attempted laparoscopic procedure; however, no mortality was reported. Conclusion : : Although it is preferable to diagnose MS preoperatively, a preoperative diagnosis is seldom possible. ERCP is both a diagnostic and therapeutic procedure of choice before definitive surgery and helps to identify any associated cystic duct anomalies in these patients.

Endoscopic sphincterotomy (EST), endoscopic papillary balloon dilation (EPBD), and endoscopic sphincterotomy plus balloon dilation (ESBD) are all techniques used to manage choledocholithiasis. We aim to analyze the efficacy and safety of these techniques for treating choledocholithiasis in patients undergoing hemodialysis (HD).We performed a retrospective study of 80 patients with end-stage renal disease (ESRD) on HD who underwent endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis management between August 1st, 2012, and December 31st, 2020, at a medical center in southern Taiwan. These patients were divided into three groups: EST (n = 21), EPBD (n = 28), and ESBD (n = 31). Post-ERCP complications, including pancreatitis, bleeding, cholangitis, and perforation, were reviewed for analysis.There were no significant among-group differences in the rate of complete stone clearance and hospitalization day after ERCP. Patients in the EST group had a higher post-ERCP complication rate than was the case in the other groups (p = 0.016). ESBD significantly reduced post-ERCP bleeding, compared with that occurring with EST (OR 0.07; 95% CI, 0.01-0.72, p = 0.026). There were no significant among-group differences in the rates of pancreatitis and cholangitis. There were no ERCP-related perforations or deaths in this study.EST, EPBD, and ESBD are efficient methods for treating choledocholithiasis in ESRD patients. ESBD was found to lead to a lower risk of bleeding than EST, and the rate of pancreatitis or cholangitis was comparable for EST and EPBD. Our results suggest that ESBD is the best choice of treatment of choledocholithiasis in patients with ESRD undergoing HD.

A 60-year-old male with cStage IVB lung cancer was treated with pembrolizumab. However, after five courses of pembrolizumab, he developed pembrolizumab-related cholangitis. Imaging studies showed enlargement and diffuse wall thickening of the gallbladder and mild dilation of the bile ducts without any obvious obstruction. As the patient experienced severe abdominal pain, we suspected bile stasis and performed biliary drainage. However, his condition did not improve, and he developed multiple liver abscesses and died during immunosuppressive therapy. Our case suggests that in ir-cholangitis, the indication and method of endoscopic retrograde cholangiopancreatography should be carefully judged.

OBJECTIVE To characterize the frequency and type of bacterial infection by culture- and immunohistochemical (IHC)-based methods and determine the impact of infection on clinical features and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome (S-CCHS). ANIMALS 168 client-owned cats with S-CCHS (cases). PROCEDURES Clinical features, bacterial culture results, culture-inoculate sources, and survival details were recorded. Cases were subcategorized by comorbidity (extrahepatic bile duct obstruction, cholelithiasis, cholecystitis, ductal plate malformation, biopsy-confirmed inflammatory bowel disease, and biopsy-confirmed pancreatitis) or treatment by cholecystectomy or cholecystoenterostomy. Culture results, bacterial isolates, Gram-stain characteristics, and IHC staining were compared among comorbidities. Lipoteichoic acid IHC staining detected gram-positive bacterial cell wall components, and toll-like receptor expression IHC reflected pathologic endotoxin (gram-negative bacteria) exposure. RESULTS Clinical features were similar among cases except for more frequent abdominal pain and lethargy in cats with positive culture results and pyrexia, abdominal pain, and hepatomegaly for cats with polymicrobial infections. Bacteria were cultured in 93 of 135 (69%) cats, with common isolates including Enterococcus spp and Escherichia coli. IHC staining was positive in 142 of 151 (94%) cats (lipoteichoic acid, 107/142 [75%]; toll-like receptor 4, 99/142 [70%]). With in-parallel interpretation of culture and IHC-based bacterial detection, 154 of 166 (93%) cats had bacterial infections (gram-positive, 118/154 [77%]; gram-negative, 111/154 [72%]; polymicrobial, 79/154 [51%]). Greater frequency of bacterial isolation occurred with combined tissue, bile, and crushed cholelith inoculates. Infection and gram-positive bacterial isolates were associated with significantly shorter long-term survival times. CLINICAL RELEVANCE S-CCHS was associated with bacterial infection, pathologic endotoxin exposure, and frequent polymicrobial infection in cats. Combined tissue inoculates improved culture detection of associated bacteria.

Candida and other fungal species play an increasing role in nosocomial infections, including cholangitis and cholangiosepsis. Early diagnosis and prompt treatment are essential in successful patient outcomes. Fluconazole is an antifungal of choice in fluconazole-sensitive Candida infections. Little information is known about the fluconazole biliary excretion. Decreased tissue penetration may be one of the possible causes of treatment failure. Due to favorable pharmacokinetics, therapeutic drug monitoring of this antifungal has not been recommended routinely. In the presented case we report the successful therapeutic drug monitoring-guided fluconazole treatment in a patient with cholangitis and cholangiosepsis caused by fluconazole-sensitive Candida spp.

Here we investigated the gender difference in murine cholangitis resembling human primary biliary cholangitis (PBC) caused by synthetic double-stranded RNA, and underlying hepatic innate immune responses. Female C57Bl/6 mice given repeated injections of polyinosinic-polycytidylic acid (poly I:C) for 24 weeks developed overt cholangitis with positive serum anti-mitochondria-M2 antibody, whereas male mice showed minimal pathological changes without induction in autoantibody. Poly I:C induced hepatic inflammatory cytokines and type-I interferons predominantly in females. Hepatic expression levels of toll-like receptor (TLR) 3 and melanoma differentiation-associated protein (MDA) 5 were equivalent in both genders; however, both mRNA and protein levels of retinoic acid-inducible gene (RIG)-I were nearly doubled in female livers. Following 4-week injections of poly I:C, not only hepatic RIG-I, but also TLR3 and MDA5 showed female-predominance. Moreover, hepatic RIG-I levels were 25% lower in ovariectomized mice, whereas supplementation of 17 β-estradiol enhanced hepatic RIG-I expression, as well as cytokine induction. These results clearly indicate that hepatic RIG-I expression is potentiated by estrogen, and triggers gender-dependent hepatic innate immune response against double-stranded RNA, which most likely play a pivotal role in the pathogenesis of autoimmune cholangiopathies including PBC.

Gallstone disease (GBS) is one of the most common diseases of modern man. It ranks third after cardiovascular diseases and diabetes mellitus. In developed countries cholelithiasis affects 10-15% of adults. In recent years the majority of these surgeries are performed using minimally invasive techniques (small-access surgery, endovideosurgery, transluminal surgery). As the number of surgeries on ALS is constantly growing, the number of patients with various postoperative problems is increasing accordingly. According to different authors, 1-2 of every 10 operated patients after cholecystectomy continue to experience discomfort of the gastrointestinal tract, pain, digestive disorders, repeated painful attacks. Gastroenterologists group such symptoms under the term "postcholecystectomy syndrome" (PCES). Recurrence of pain in half of the cases occurs within the first year after surgery, but it can also occur in the long term.

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease, which is associated with an increased risk of cholangiocarcinoma (CCA). Novel markers, to complement or replace CA19-9, are urgently needed for the screening of PSC-associated biliary neoplasia. Previous studies have suggested that serum trypsinogen-2 and human chorionic gonadotropin β-subunit (hCGβ) may serve as such markers. Using highly specific in-house immunoassays, we studied trypsin(ogen)-2 and -3, SPINK1 and hCGβ in bile samples of 214 patients, referred for endoscopic retrograde cholangiography. We found that biliary trypsinogen-2 was decreased (p = 0.027) and hCGβ was elevated (p < 0.001) in PSC patients who were diagnosed 1.6 years (median, range 0.1–8.8 years) later with CCA or in whom biliary dysplasia was observed at least twice in brush cytology (n = 11) as compared to PSC patients without CCA or repeated dysplasia (n = 171). The other studied markers did not show significant differences between these groups. Our results warrant further evaluation of hCGβ as a predictive marker for PSC-associated biliary neoplasia.

Management of complicated cholelithiasis (gallstone disease) in elderly patients is often limited to the use of only minimally invasive interventions.Case report. We report three clinical cases of gallstone disease complications in patients over 75 years old who had previously undergone minimally invasive surgery and who was refused radical surgical treatment due to comorbidity. In two patients, this led to the development of purulent cholangitis and multiple organ failure, which required emergency hospitalization. At the first stage, biliary drainage was performed; then the multidisciplinary team managed to stabilize the condition of the patient; at the second stage, biliodigestive anastomoses were formed through laparotomic access on a loop turned off by the Ru. Complete relief of symptoms was achieved and no relapse was observed.In another case, cholecystoduodenal fistula with stone migration and complete obstruction of the small intestine was found during laparotomy in an asymptomatic patient hospitalized for elective surgery.Discussion. Comorbidity should not be considered as an absolute contraindication to radical surgery of complicated cholelithiasis in elderly patients: gallstone disease complications in most cases exceed the risks of surgical intervention. Radical surgery of complicated gallstone disease in patients over 75 years old is possible in condition of patient management by a multidisciplinary team.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive fibro-stenotic strictures and destruction of the biliary tree. Currently, there is no effective treatment which can delay its progression or ameliorate the transplant-free survival. Moreover, a major chontroversy in PSC is whether to use UDCA. More recently, novel pharmacological agents emerged aiming at: i) modulation of bile composition; ii) immunomodulation; iii) targeting the gut microbiome; iv) targeting fibrosis. Successful PSC therapy, however, will be most likely a personalized combination of different drugs plus endoscopic treatment. This review aims at offering an overview on the experimental pharmacological strategies currently exploited for PSC treatment.

Cholestasis and obstructive jaundice can be extrahepatic or intrahepatic. Here we present one case with calculous cholecystitis who presenting with repeated obstructive jaundice and without bile duct dilation. The patient received laparoscopic cholecystectomy, and cystohepatic duct was identified intraoperatively, there was no cholestasis or obstructive jaundice postoperatively. Cystohepatic duct is a rare biliary anomaly observed in 0.7% of all surgical cases and in 1.5% of all cadaveric dissections. The cystohepatic duct can be the bridge of calculous cholecystitis complicating cholangitis and obstructive jaundice, here we for the first time presented this entity.