Late cholangitis after pancreatoduodenectomy: A common complication with or without anatomical biliary obstruction.

BACKGROUND: Postoperative cholangitis is a common complication after pancreatoduodenectomy that can occur with or without anatomical biliary obstruction. This study aimed to investigate the incidence, diagnosis, treatment, and risk factors of cholangitis after pancreatoduodenectomy. METHODS: We performed a retrospective cohort study of consecutive patients who underwent pancreatoduodenectomy in 2 Dutch tertiary pancreatic centers (2010-2019). Primary outcome was postoperative cholangitis, defined as systemic inflammation with abnormal liver tests without another focus of infection, at least 1 month after resection. Diagnostic and therapeutic strategies were evaluated. Two types of postoperative cholangitis were distinguished; obstructive cholangitis (benign stenosis of the hepaticojejunostomy) and nonobstructive cholangitis. Potential risk factors were identified using logistic regression analysis. RESULTS: Postoperative cholangitis occurred in 93 of 900 patients (10.3%). Median time to first episode of cholangitis was 8 months (interquartile range 4-16) after pancreatoduodenectomy. Multiple episodes of cholangitis occurred in 44 patients (47.3%) and readmission was necessary in 83 patients (89.2%). No cholangitis-related mortality was observed. Obstructive cholangitis was seen in 37 patients (39.8%) and nonobstructive cholangitis in 56 patients (60.2%). Surgery was performed for cholangitis in 7 patients (7.5%) and consisted of revision of the hepaticojejunostomy or elongation of the biliary limb. Postoperative biliary leakage (odds ratio 2.56; 95% confidence interval 1.42-4.62; P = .0018) was independently associated with postoperative cholangitis. CONCLUSION: Postoperative cholangitis unrelated to cancer recurrence was seen in 10% of patients after pancreatoduodenectomy. Nonobstructive cholangitis was more common than obstructive cholangitis. Postoperative biliary leakage was an independent risk factor.

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

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

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.

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

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

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

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

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

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

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

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

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

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

The Clinical Features of Late Postoperative Cholangitis After Hepaticojejunostomy Brought on by Conditions other than Cancer Recurrence.

PURPOSE: Postoperative cholangitis and anastomotic strictures (AS) are long-term complications of biliary-enteric anastomosis (BEA). METHODS: We retrospectively reviewed data of patients who underwent bile duct resection with or without hepatectomy and investigated the risk factors for postoperative cholangitis, benign AS, and incidence of Clavien-Dindo (C-D) >Grade III complications. RESULTS: Overall, data of 189 patients (115 men and 74 women) were retrospectively analyzed. The median patient age was 73 years. Thirty-five patients (18.5%) developed postoperative cholangitis, and 16 (8.4%) developed postoperative AS. Male sex and serious postoperative complications (C-D ≥ Grade III) were independent risk factors for cholangitis. The incidence of serious postoperative complications was 32.3%. Hypertension, preoperative biliary drainage, C-reactive protein-albumin ratio ≥.22, and bile duct resection with hepatectomy were potential risk factors for serious postoperative complications. CONCLUSIONS: The incidence rates of postoperative cholangitis and AS after BEA were 18.5% and 8.4%, respectively. Male sex and serious postoperative complications (C-D ≥ Grade III) were independent risk factors for postoperative cholangitis.

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

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

Predisposing risk factors for isolated bile leakage after pancreaticoduodenectomy.

AIM: Isolated bile leakage (IBL) from hepaticojejunostomy, following pancreaticoduodenectomy, is a serious complication that increases morbidity and mortality. We aimed to assess the frequency of IBL development after pancreaticoduodenectomy and its underlying factors. MATERIALS AND METHODS: Patients who underwent pancreaticoduodenectomy for pancreatic diseases between January 2005 and January 2016 were retrospectively evaluated. Patients were dichotomized according to those with and without postoperative IBL. RESULTS: In the 111 patients who underwent pancreaticoduodenectomy during our study period, 8 patients (7.2%; 5 men/3 women) developed IBL. Risk of IBL development was significantly elevated among male patients, those with preoperative serum albumin < 3.5 g/dL, and those with previous cholangitis (P < 0.05). DISCUSSION: Male sex, preoperatively low levels of serum albumin, and preoperative history of cholangitis can be listed as risk factors for IBL development. Physicians should pay attention to the risk of postoperative IBL development in such patients. KEY WORDS: Isolated bile leakage, Pancreaticoduodenectomy, Morbidity.

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

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

Incidence and Mechanism of Refractory Postoperative Cholangitis After Hepatectomy with Hepaticojejunostomy.

INTRODUCTION: Malignant tumors, such as hilar cholangiocarcinoma, have shown improved long-term outcomes, and measures to prevent late postoperative complications are important. Postoperative cholangitis after hepatectomy with hepaticojejunostomy (HHJ) may occur and can significantly decrease the quality of life. However, there are few reports on the incidence and pathogenesis of postoperative cholangitis after HHJ. METHODS: We retrospectively reviewed 71 cases post HHJ at Tokyo Medical and Dental University Hospital from January 2010 to December 2021. Cholangitis was diagnosed using the Tokyo Guideline 2018. Cases due to tumor recurrence around the hepaticojejunostomy (HJ) were excluded. Patients with three or more episodes of cholangitis were classified as the "refractory cholangitis group" (RC group). RC group patients were divided into a "stenosis group" and "non-stenosis group" according to intrahepatic bile duct dilatation at the onset of cholangitis. Their clinical characteristics and risk factors were analyzed. RESULTS: Cholangitis occurred in 20 patients (28.1%), with 17 (23.9%) in the RC group. Most patients in the RC group developed their first episode within the first postoperative year. The stenosis group consisted of 6 patients, and their cholangitis was treated with repeated anastomotic dilatation and stent replacement. In the non-stenosis group, cholangitis was relatively mild and treated with antibiotics. Hepatobiliary scintigraphy for these cases showed bile congestion in the jejunum near the site of the hepaticojejunostomy. CONCLUSION: There are two types of postoperative cholangitis, each with different pathogenesis and treatment. It is essential to assess anastomotic stenosis early and provide the necessary treatment.

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

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

Risk factors and outcomes for cholangitis after hepatic resection.

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

Primary biliary cholangitis: Epidemiology, prognosis, and treatment.

Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease characterized by a destructive, small duct, and lymphocytic cholangitis, and marked by the presence of antimitochondrial antibodies. The incidence and prevalence of PBC vary widely in different regions and time periods, and although disproportionally more common among White non-Hispanic females, contemporary data show a higher prevalence in males and racial minorities than previously described. Outcomes largely depend on early recognition of the disease and prompt institution of treatment, which, in turn, are directly influenced by provider bias and socioeconomic factors. Ursodeoxycholic acid remains the initial treatment of choice for PBC, with obeticholic acid and fibrates (off-label therapy) reserved as add-on therapy for the management of inadequate responders or those with ursodeoxycholic acid intolerance. Novel and repurposed drugs are currently at different stages of clinical development not only for the treatment of PBC but also for its symptomatic management. Here, we summarize the most up-to-date data regarding the epidemiology, prognosis, and treatment of PBC, providing clinically useful information for its holistic management.

Risk Factors for Cholangitis After Pancreatoduodenectomy: A Systematic Review.

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

Characteristics and clinical outcomes of acute cholangitis in older patients.

PURPOSE: Few studies are available on older patients with acute cholangitis. In this study, we aimed to examine the clinical characteristics of older patients with acute cholangitis. METHODS: Patients aged 65 years and over who were diagnosed with acute cholangitis between February 2019 and August 2022 were analyzed retrospectively. Patients eligible for the study were divided into two groups as those aged ≥ 80 years (octogenarian) and those aged 65-79 years (non-octogenarian). These two groups were then compared for many clinical characteristics. In addition, factors associated with in-hospital mortality were identified. Finally, a subgroup analysis was performed in patients with non-malignant etiology. RESULTS: Of a total of 309 enrolled patients, 120 (38.8%) were in the octogenarian group and 189 (61.2%) were in the non-octogenarian group. The mean age was 77.2 ± 8.0 years and 51.8% were women. Severe disease and intensive care unit admission rates were higher in the octogenarian group (p = 0.035 and p = 0.002, respectively), but there was no significant difference in the rate of in-hospital mortality (p = 0.146). Malignant etiology (OR 2.990, 95% CI 1.131-7.904) and hypoalbuminemia (OR 0.824, 95% CI 0.751-0.903) were independent risk factors for in-hospital mortality. In the subgroup analysis of non-malignant etiology, the octogenarian group had a significantly higher in-hospital mortality rate than the non-octogenarian group (8.8% vs. 3.2%, p = 0.048). CONCLUSIONS: Among older patients with acute cholangitis, clinicians should closely monitor those aged 80 years and over, as well as those with malignant etiology and hypoalbuminemia, due to their high risk of serious clinical events.

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

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

Risk factors for postoperative cholangitis after pancreaticoduodenectomy and evaluation of internal stenting on hepaticojejunostomy: A single-center propensity score-based analysis.

BACKGROUND/PURPOSE: This retrospective study aimed to investigate the risk factors for postoperative cholangitis (POC) after pancreaticoduodenectomy (PD) and the efficacy of stenting on hepaticojejunostomy (HJ). METHODS: We investigated 162 patients. Postoperative cholangitis occurring before and after discharge was defined as early-onset POC (E-POC) and late-onset POC (L-POC), respectively. Risk factors for E-POC and L-POC were identified using univariate and multivariate logistic regression analyses. Propensity score matching (PSM) between the stenting group (group S) and the non-stenting group (group NS), and subgroup analysis in patients with risk factors were performed to evaluate the efficacy of stenting on HJ in preventing POC. RESULTS: Body mass index (BMI) ≥ 25 kg/m2 and preoperative non-biliary drainage (BD) were risk factors for E-POC and L-POC, respectively. PSM analysis revealed that E-POC occurrence was significantly higher in group S than in group NS (P = .045). In the preoperative non-BD group (n = 69), E-POC occurrence was significantly higher in group S than in group NS (P = .025). CONCLUSIONS: BMI ≥ 25 kg/m2 and preoperative non-BD status were risk factors for E-POC and L-POC, respectively. Stenting on HJ implants did not prevent POC after PD.