Acute suppurative terminal cholangitis: Clinical characteristics of a new subtype of acute cholangitis.

BACKGROUND: Acute suppurative terminal cholangitis (ASTC) is rarer than acute obstructive cholangitis and is not well studied. To explore this subtype of acute cholangitis, we described our clinical experience with ASTC. METHODS: We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020. We analyzed their clinical characteristics, including etiology, clinical manifestations, imaging features, treatment and prognosis. RESULTS: A total of 32 ASTC patients were included in the analysis. The majority of the patients had a history of biliary operations, and clinical manifestations were occult and atypical. The positive rate of bacterial culture was 46.9%. All the patients had typical imaging features on computed tomography and magnetic resonance imaging. Treatment with effective antibiotics was provided as soon as diagnosis was established. After treatment, most patients had a good outcome. Elevated levels of total bilirubin, aspartate aminotransferase, procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis. CONCLUSIONS: Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis, and that earlier diagnosis and more personalized treatments are needed.

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.

The association between sonographic common bile duct dilatation and outcomes in emergency department patients with cholangitis.

BACKGROUND: The presentation of the patient with acute cholangitis (AC) ranges from mild illness to life-threatening shock. Therefore, prompt diagnosis and treatment are critical. Abdominal ultrasound (US) is the imaging of choice to locate bile duct dilatation. Other modalities include abdominal computed tomography (CT) or endoscopic retrograde cholangiopancreatography (ERCP). OBJECTIVES: To determine whether sonographic common bile duct dilatation in emergency department (ED) patients with AC predicts outcomes including sepsis, hospital length of stay (LOS), admission to the intensive care unit (ICU), time to ERCP, and mortality. METHODS: Electronic medical records of all patients hospitalized in a tertiary care medical center between July 2012-February 2021 with a discharge diagnosis of cholangitis were assessed. Patients were dichotomously classified as CBD dilated or CBD non-dilated based on ultrasound. Dilation was defined as CBD larger than 6 mm in patients younger than 60 or larger than 6 mm + 1 mm per decade in patients over 60. RESULTS: The study included 271 patients- 172 with CBD dilation versus 99 without. Mean LOS was 9.92 days for those with a dilated CBD versus 13.4 days without. The mean time to ERCP was 4.26 days for those with a dilated CBD versus 6.56 days without. Sepsis, mortality, and ICU admission were scarce and there was no statistically significant difference between the cohorts. CONCLUSION: Patients with a dilated CBD per the abdominal US performed during the patient's ED stay, underwent ERCP earlier, and were hospitalized fewer days than patients without CBD dilation.

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

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

Liver cirrhosis is a risk factor for poor prognosis of acute cholangitis caused by choledocholithiasis.

INTRODUCTION AND OBJECTIVES: Acute cholangitis, which is characterized by biliary infection and acute liver injury, may impact cirrhosis prognosis. However, the prognosis itself remains unclear. MATERIALS AND METHODS: This multicenter retrospective cohort study compared the mortality and liver function change between patients with and without cirrhosis who underwent endoscopic treatment for acute cholangitis caused by choledocholithiasis between January 2004 and December 2019. RESULTS: We analyzed 699 patients, 44 of whom had cirrhosis. The cirrhotic group had a significantly higher 30-day mortality rate than the noncirrhotic group (14% vs. 1%; P < 0.001). The cirrhotic group also had significantly lower total bilirubin and albumin recovery. However, all patients with cirrhosis who survived achieved total-bilirubin recovery, and 91% achieved albumin recovery within 90 days. In multivariable Cox regression analysis, the independent risk factors for total-bilirubin recovery included cirrhosis (hazard ratio, 0.37; 95%CI, 0.24‒0.58; P < 0.001) and high total-bilirubin level (0.46; 95%CI, 0.34‒0.60; P < 0.001), whereas those for albumin recovery were cirrhosis (0.51; 95%CI, 0.33‒0.79; P = 0.002), high age (0.62; 95%CI, 0.47‒0.82; P < 0.001), organ dysfunction (0.62; 95%CI, 0.39‒0.96; P = 0.03), low albumin level (0.57; 95%CI, 0.36‒0.91; P = 0.02), and high C-reactive protein level (0.73; 95%CI, 0.56‒0.95; P = 0.02). CONCLUSIONS: Patients with cirrhosis complicated with acute cholangitis had poor prognosis. Recovery of liver function after endoscopic treatment was slow; nevertheless, most patients who survived could recover within 90 days.

Practical management of primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic and cholestatic liver disease of autoimmune pathogenesis that mainly affects middle-aged women. Patients show elevated alkaline phosphatase and bilirubin levels as the disease progresses. The main symptoms of the disease are pruritus and fatigue, which interfere with the quality of life of patients. Progressive damage leading to end stage liver disease could require liver transplantation. Despite the efficacy of ursodeoxycholic acid (UDCA), the current standard of care for PBC, up to 40% of patients have an inadequate response to the treatment, requiring a second-line therapy. Obeticholic acid is the only second-line treatment approved for PBC in combination with UDCA in adults with an inadequate response to UDCA, or as monotherapy in patients intolerant to UDCA. Although different clinical guidelines for the diagnosis and management of PBC have been published, PBC is still challenging for many physicians. In this article we briefly review the main characteristics of the disease and include a practical user-friendly algorithm for the diagnosis and management of PBC developed by Spanish PBC experts and based on the European Association for the Study of the Liver recommendations.

[Guidelines on the diagnosis and management of primary biliary cholangitis (2021)].

In 2015, the Chinese Society of Hepatology and Chinese Society of Gastroenterology issued a consensus on the diagnosis and management of primary biliary cholangitis (PBC). In the past years, more clinical studies have been reported in the field of PBC. To provide guidance to the clinical diagnosis and management of patients with PBC, the Chinese Society of Hepatology invited a panel of experts to assess the new clinical evidence and formulated the current guidelines which comprises 26 clinical recommendations.

Nanoparticle-mediated targeting of autoantigen peptide to cross-presenting liver sinusoidal endothelial cells protects from CD8 T-cell-driven autoimmune cholangitis.

Autoimmune diseases are caused by adaptive immune responses to self-antigens. The development of antigen-specific therapies that suppress disease-related, but not unrelated immune responses in general, is an important goal of biomedical research. We have previously shown that delivery of myelin peptides to liver sinusoidal endothelial cells (LSECs) using LSEC-targeting nanoparticles provides effective protection from CD4 T-cell-driven autoimmune encephalomyelitis. Here, we investigated whether this methodology might also serve antigen-specific treatment of a CD8 T-cell-driven autoimmune disease. As a model for CD8 T-cell-mediated autoimmunity, we used OT-1 T-cell-driven cholangitis in K14-OVAp mice expressing the cognate MHC I-restricted SIINFEKL peptide in cholangiocytes. To study whether peptide delivery to LSECs could modulate cholangitis, SIINFEKL peptide-conjugated nanoparticles were administered intravenously one day before transfer of OT-1 T cells; five days after cell transfer, liver pathology and hepatic infiltrates were analysed. SIINFEKL peptide-conjugated nanoparticles were rapidly taken up by LSECs in vivo, which effectively cross-presented the delivered peptide on MHC I molecules. Intriguingly, K14-OVAp mice receiving SIINFEKL-loaded nanoparticles manifested significantly reduced liver damage compared with vehicle-treated K14-OVAp mice. Mechanistically, treatment with LSEC-targeting SIINFEKL-loaded nanoparticles significantly reduced the number of liver-infiltrating OT-1 T cells, which up-regulated expression of the co-inhibitory receptor PD-1 and down-regulated cytotoxic effector function and inflammatory cytokine production. These findings show that tolerogenic LSECs can effectively internalize circulating nanoparticles and cross-present nanoparticle-bound peptides on MHC I molecules. Therefore, nanoparticle-mediated autoantigen peptide delivery to LSECs might serve the antigen-specific treatment of CD8 T-cell-driven autoimmune disease.

ERCP is more challenging in cases of acute biliary pancreatitis than in acute cholangitis - Analysis of the Hungarian ERCP registry data.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an important therapeutic modality in acute biliary pancreatitis (ABP) cases with cholangitis or ongoing common bile duct obstruction. Theoretically, inflammation of the surrounding tissues would result in a more difficult procedure. No previous studies examined this hypothesis. OBJECTIVES: ABP and acute cholangitis (AC) without ABP cases were compared to assess difficulty of ERCP. METHODS: The rate of successful biliary access, advanced cannulation method, adverse events, cannulation and fluoroscopy time were compared in 240 ABP cases and 250 AC cases without ABP. Previous papillotomy, altered gastroduodenal anatomy, and cases with biliary stricture were excluded. RESULTS: Significantly more pancreatic guidewire manipulation (adjusted odds ratio (aOR) 1.921 [1.241-2.974]) and prophylactic pancreatic stent use (aOR 4.687 [2.415-9.098]) were seen in the ABP than in AC group. Average cannulation time in the ABP patients (248 vs. 185 s; p = 0.043) were longer than in AC cases. No difference was found between biliary cannulation and adverse events rates. CONCLUSION: ERCP in ABP cases seem to be more challenging than in AC. Difficult biliary access is more frequent in the ABP cases which warrants the involvement of an experienced endoscopist.

ASGE guideline on the management of cholangitis.

Cholangitis is a GI emergency requiring prompt recognition and treatment. The purpose of this document from the American Society for Gastrointestinal Endoscopy's (ASGE) Standards of Practice Committee is to provide an evidence-based approach for management of cholangitis. This document addresses the modality of drainage (endoscopic vs percutaneous), timing of intervention (<48 hours vs >48 hours), and extent of initial intervention (comprehensive therapy vs decompression alone). Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to formulate recommendations on these topics. The ASGE suggests endoscopic rather than percutaneous drainage and biliary decompression within 48 hours. Additionally, the panel suggests that sphincterotomy and stone removal be combined with drainage rather than decompression alone, unless patients are too unstable to tolerate more extensive endoscopic treatment.

First case report of acute cholangitis secondary to Cronobacter sakazakii.

INTRODUCTION: Cronobacter sakazakii is an opportunistic Gram-negative, rod-shaped bacterium which may be a causative agent of meningitis in premature infants and enterocolitis and bacteremia in neonates and adults. While there have been multiple cases of C. sakazakii infections, there have been no acute cholangitis cases reported in humans. CASE PRESENTATION: An 81-year-old male with a past medical history of basal cell carcinoma, alcoholic liver cirrhosis, transjugular intrahepatic portosystemic shunt procedure, complicated by staphylococcus bacteremia, pituitary tumor, glaucoma, and hypothyroidism presented to the emergency room with the complaint of diffuse and generalized 10/10 abdominal pain of 1 day's duration. There was a concern for pancreatitis, acute cholangitis, and possible cholecystitis, and the patient underwent a percutaneous cholecystostomy tube placement. Blood cultures from admission and biliary fluid cultures both grew C. sakazakii. The patient was treated with a carbapenem and clinically improved. CONCLUSIONS: The case study described a patient with multiple medical comorbidities that presented with C. sakazakii bacteremia and cholangitis. While this bacterium has been implicated in other infections, we believe this is the first time the bacteria is being documented to have caused acute cholangitis.

Antibiotic Therapy of 3 Days May Be Sufficient After Biliary Drainage for Acute Cholangitis: A Systematic Review.

BACKGROUND: The optimal antibiotic therapy duration for cholangitis is unclear. Guideline recommendations vary between 4 and 14 days after biliary drainage. Clinical observations and some evidence however suggest that shorter antibiotic therapy may be sufficient. OBJECTIVE: To compare the effectiveness and safety of short-course therapy of ≤ 3 days with long-course therapy of ≥ 4 days after biliary drainage in cholangitis patients. METHODS: We searched the databases PubMed, EMBASE, Cochrane Library, and trial registers for literature up to August 5, 2020. RCTs and observational studies including case series reporting on antibiotic therapy duration for acute cholangitis were eligible for inclusion. Two reviewers independently evaluated study eligibility, extracted data, assessed risk of bias and quality of evidence. A meta-analysis was planned if the included studies were comparable with regard to important study characteristics. Primary outcomes included recurrent cholangitis, subsequent other infection, and mortality. RESULTS: We included eight studies with 938 cholangitis patients. Four observational studies enrolled patients treated for ≤ 3 days. Recurrent cholangitis occurred in 0-26.8% of patients treated with short-course therapy, which did not differ from long-course therapy (range 0-21.1%). Subsequent other infection and mortality rates were also comparable. Quality of available evidence was very low. CONCLUSION: There is no high-quality evidence available to draw a strong conclusion, but heterogeneous observational studies suggest that antibiotic therapy of ≤ 3 days is sufficient in cholangitis patients with common bile duct stones.

Late postoperative complications of congenital biliary dilatation in pediatric patients: a single-center experience of managing complications for over 20 years.

PURPOSE: To investigate late complications after surgery for congenital biliary dilatation (CBD). METHODS: We retrospectively reviewed the patients treated for late postoperative complications of extrahepatic bile duct resection with bilioenteric anastomosis for CBD at our hospital between 1999 and 2019. RESULTS: Twenty-seven complications, including bile duct stenosis with (n = 19) or without (n = 3) hepatolithiasis, remnant intrapancreatic bile duct (n = 2), intestinal obstruction (n = 2), and refractory cholangitis (n = 1) were treated in 26 patients. The median age at radical surgery and the initial treatment of complications was 3 years, 2 months and 14 years, 5 months, respectively. The median period from radical surgery to initial treatment of complications was 7 years, 1 month. Before 2013, bile duct stenosis was initially treated with bile duct plasty (n = 11) or hepatectomy (n = 3), and 71.4% (n = 10) of patients needed further treatment; after 2013, double-balloon endoscopic retrograde cholangiography (DBERC) was used (n = 8), and 25% (n = 2) of patients needed further treatment. Patients with remnant intrapancreatic bile duct, intestinal obstruction, and refractory cholangitis required surgery. CONCLUSION: Long-term follow-up is necessary after surgery for congenital biliary dilatation. DBERC is thus considered to be useful for bile duct stenosis management.

[Guidelines on the diagnosis and management of primary biliary cholangitis (2021)].

In 2015, the Chinese Society of Hepatology and Chinese Society of Gastroenterology issued the consensus on the diagnosis and management of primary biliary cholangitis (PBC). In the past years, more clinical studies have been reported in the field of PBC. To provide guidance to the clinical diagnosis and management of patients with PBC, the Chinese Society of Hepatology invited a panel of experts assessed the new clinical evidence and formulated the current guidelines which comprises 26 clincal recommendations.

[Recommendations for diagnosis and treatment of primary biliary cholangitis in China (2021)].

Primary biliary cholangitis is a chronic autoimmune cholestatic disease with a progressive course. This disease is not rare in China, but standardized diagnosis and treatment for primary biliary cholangitis are insufficient. Based on the evidence and guidelines from China and other countries, Rheumatology Branch of Chinese Medical Association developed the recommendations of diagnosis and treatment for primary biliary cholangitis in China. The aim is to help clinicians recognize clinical characters, therapeutic selection and prognosis judgement of primary biliary cholangitis, which will contribute to make diagnosis in time, to select treatment properly and to manage follow-up scientifically.

Prognostic factors associated with six month mortality of critically ill elderly patients admitted to the intensive care unit with severe acute cholangitis.

BACKGROUND: Little is known about the outcomes of elderly patients admitted to the intensive care unit (ICU) with severe acute cholangitis (SAC). The objectives were to describe the 6-month mortality in patients with SAC ≥75 years and to identify factors associated with this mortality. METHODS: Bi-center retrospective study of critically ill elderly patients with SAC conducted between 2013 and 2017. Demographic and clinical variables of ICU and hospital stays with a 6-month follow-up were analyzed. RESULTS: 85 patients, with a median [Q1-Q3] age of 83 [80-89] years were enrolled of whom 51 (60%) were men. SAC was due to choledocholithiasis in 72 (85%) patients. Median [Q1-Q3] ICU length of stay was 3 [2-6] days. Median [Q1-Q3] admission SAPS II was 50 [42-70]. The ICU and 6-month mortality rates were 18% and 48% respectively. Multivariate analysis showed that malnutrition (OR = 34.5, 95% CI [1.4-817.9]) and a decrease in SOFA score at 48 h (OR by unit 0.7, 95% CI [0.5-0.9]) were associated with higher 6-month mortality. CONCLUSION: In their decision-making process, ICU physicians and hepato-pancreato-biliary surgeons could use these data to estimate the probability of survival of an elderly patient presenting with SAC and to offer time-limited trials of intensive care. TRIAL REGISTRATION: NCT03831529.

Drivers of Hospital Readmission and Early Liver Transplant after Kasai Portoenterostomy.

BACKGROUND: Kasai portoenterostomy (KPE) remains the first-line operation for patients with biliary atresia (BA), but ultimately fails in up to 60% of cases. This study sought to identify factors contributing to hospital readmission and early liver transplant. METHODS: The Nationwide Readmissions Database from 2010 to 2014 was used to identify patients with BA who underwent KPE on index admission. Patient factors, hospital characteristics, and complications of BA were compared by readmission rates and rate of liver transplant within 1 y. The results were weighted for national estimates. RESULTS: Nine hundred and sixty three patients were identified. The readmission rate within 30-d was 36% (n = 346) and within 1-y was 67% (n = 647). Only 9% (n = 90) received a liver transplant within a year. The most common complications after KPE were cholangitis in 58%, decompensated cirrhosis in 54%, and recurrent jaundice in 34%. Male patients (OR 1.5, P = 0.02) with comorbid gastrointestinal anomalies (OR 2.1, P < 0.01) from lower income households (OR 4.6, P < 0.01) and early development of cirrhosis (OR 3.0, P < 0.01) were more likely to be readmitted. Liver transplant was more common in men (OR 4.0, P < 0.01) and those from lower income households (OR 5.2, P < 0.01) with decompensated cirrhosis (OR 8.6, P < 0.01), cholangitis (OR 5.0, P < 0.01), or sepsis (OR 5.7, P < 0.01) on index admission. CONCLUSIONS: This is the first nationwide study to evaluate readmissions in patients with BA undergoing KPE. Although KPE is a lifesaving procedure, hospital readmission rates are high and complications are common. Cholangitis, early progression of cirrhosis, and infections are highly associated with readmission and failure of KPE.

Clinical Ontologies Improve Case Finding of Primary Biliary Cholangitis in UK Primary and Secondary Care.

INTRODUCTION: PBC registries in the UK focus on data from secondary care without clear coordinated contribution from primary care. The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) receives data from > 500 primary care practices (PCPs). Notably, the Lancet commissioning group is extracting data from the RCGP RSC database to shape UK policy on liver disease. AIMS: To create a novel ontology to facilitate PBC case finding from primary care provider (PCP) records. METHODS: RCGP RSC data were collected from participating PCPs in the county of Surrey, UK. PBC diagnostic criteria of the AASLD and EASL guidelines were used to develop 725 data codes to facilitate patient record searches. A scoring system built into the ontology allowed categorization of cases as PBC definite, PBC probable, and PBC unlikely. RESULTS: A total of 218,099 records were searched from participating PCPs. Of these, there were 58 PBC definite, 2317 PBC probable, and 215,724 PBC unlikely patients. There were 32 PBC definite patients who did not match to our regional PBC database and were henceforth included as new-found cases. Two of these cases were not labeled as PBC by the PCP. From the PBC unlikely group, 7/215,724 (0.003%) patients were labeled as PBC in secondary care records; however, none of them were coded as having PBC by their PCPs. CONCLUSIONS: Utilization of the UK National RCGP RSC database supported by novel ontology score has successfully helped us identify (i) new cases of PBC not known to local/regional secondary care providers and (ii) de novo PBC cases. There are many PBC probable cases whose data merit further careful evaluation.

Endoscopic Retrograde Cholangiopancreatography-Related Complications and Their Management Strategies: A "Scoping" Literature Review.

Endoscopic retrograde cholangiopancreatography (ERCP) is a well-known procedure with both diagnostic and therapeutic utilities in managing pancreaticobiliary conditions. With the advancements of endoscopic techniques, ERCP has become a relatively safe and effective procedure. However, as ERCP is increasingly being utilized for different advanced techniques, newer complications have been noticed. Post-ERCP complications are known, and mostly include pancreatitis, infection, hemorrhage, and perforation. The risks of these complications vary depending on several factors, such as patient selection, endoscopist's skills, and the difficulties involved during the procedure. This review discusses post-ERCP complications and management strategies with new and evolving concepts.

Acute biliary interventions.

Acute biliary conditions include cholangitis, obstruction, and biliary leakage. All these conditions may lead to severe biliary sepsis, which can be life threatening. Infected obstructed cholangitis is a medical emergency that requires active medical therapy and early biliary decompression is recommended. This article provides an overview of the clinical presentations and management of biliary sepsis. The technique, clinical applications, and outcomes of percutaneous transhepatic biliary drainage and those related to gall bladder drainage are highlighted. Future alternatives to conventional biliary drainage are discussed.