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Ascending cholangitis

Ascending cholangitis, also known as acute cholangitis, is a potentially life-threatening bacterial infection of the biliary tree that arises from obstruction of the bile ducts, most commonly due to gallstones (choledocholithiasis).^[1] This condition leads to bacterial ascension from the duodenum into the biliary system, causing inflammation and possible systemic sepsis.^[2] It affects fewer than 200,000 individuals annually in the United States, with a peak incidence in those aged 50 to 60 years and no significant gender predominance.^[1] The primary etiology involves partial or complete biliary obstruction, which increases intraductal pressure and facilitates bacterial proliferation and translocation into the bloodstream.^[1] Common causative pathogens include Escherichia coli and Klebsiella species, though other bacteria such as Enterococcus and anaerobes can be involved.^[1] Beyond gallstones, which account for the majority of cases, contributing factors include benign strictures, malignant tumors (e.g., cholangiocarcinoma or pancreatic cancer), parasitic infections (e.g., Clonorchis sinensis in endemic areas), and iatrogenic causes like post-endoscopic retrograde cholangiopancreatography (ERCP) complications occurring in 0.5% to 2.4% of procedures.^[2] Risk factors encompass prior biliary interventions, sclerosing cholangitis, HIV infection, and travel to regions with parasitic endemicity.^[3] Clinically, ascending cholangitis manifests as a spectrum from mild to severe infection, with the classic presentation known as Charcot's triad—fever, right upper quadrant abdominal pain, and jaundice—observed in approximately 25% to 30% of cases.^[1] Fever occurs in about 90% of patients, often accompanied by chills, while jaundice and pain are present in 60% to 70%.^[1] In severe cases, Reynolds' pentad, which adds hypotension and altered mental status indicative of septic shock, is rarely observed (less than 5%).^[2] Additional symptoms may include nausea, vomiting, dark urine, and pale stools due to cholestasis.^[3] Without prompt intervention, complications such as hepatic abscesses, multiorgan failure, or overwhelming sepsis can develop.^[1] Diagnosis relies on a combination of clinical suspicion, laboratory findings, and imaging, guided by the Tokyo Guidelines 2018 (TG18), which classify severity as mild, moderate, or severe based on systemic inflammation (e.g., fever >38°C or leukocytosis), cholestasis (e.g., total bilirubin ≥2 mg/dL), and biliary dilatation or evidence of etiology on imaging.^[4] Laboratory tests typically reveal leukocytosis, elevated liver enzymes (e.g., alkaline phosphatase, gamma-glutamyl transferase), hyperbilirubinemia, and positive blood cultures in 20% to 70% of cases.^[1] Imaging modalities include abdominal ultrasound (first-line for detecting dilatation or stones), magnetic resonance cholangiopancreatography (MRCP) for detailed anatomy, or ERCP for both diagnosis and therapeutic intervention.^[1] Management prioritizes rapid resuscitation, antibiotics, and biliary decompression to prevent mortality, which exceeds 50% without drainage but drops below 10% with timely treatment.^[1] Initial therapy involves intravenous fluids, broad-spectrum antibiotics (e.g., piperacillin-tazobactam or fluoroquinolones covering gram-negative enteric organisms), and supportive care in an intensive care setting for severe cases.^[2] Biliary drainage via ERCP is the gold standard, achieving success in 94% to 98% of procedures, with percutaneous transhepatic cholangiography as an alternative for failed ERCP.^[1] In mild cases, drainage can be delayed 24 to 48 hours, but urgent intervention is required for moderate to severe presentations.^[2] Long-term prognosis is favorable with early intervention, though recurrent episodes may necessitate cholecystectomy or addressing underlying strictures.^[3]

Background

Definition and epidemiology

Ascending cholangitis, also known as acute cholangitis, is a life-threatening bacterial infection of the biliary tract that occurs when obstruction allows bacteria to ascend retrogradely from the duodenum into the bile ducts.^[1] This condition typically arises in the context of biliary obstruction, most commonly due to choledocholithiasis, leading to inflammation and potential systemic complications if untreated.^[5] Epidemiologically, ascending cholangitis is relatively uncommon, with an incidence of 0.3% to 1.6% among patients hospitalized for gallstone disease.^[6] In the United States, analyses estimate approximately 10,000 to 50,000 cases annually, though prevalence rates per 100,000 hospital admissions have shown a slight increase, from approximately 30 in 2005 to higher figures in recent years.^[1]^[7] Globally, incidence rates are comparable, with a study in the Netherlands estimating 28 cases per 100,000 individuals annually.^[8] The condition predominantly affects older adults, with a mean age at presentation of 50 to 60 years, and a higher burden observed in those over 60 due to increasing gallstone prevalence in aging populations.^[1] There is no significant gender disparity, with males and females affected equally, though associations exist with comorbidities such as diabetes and prior biliary interventions that elevate risk in susceptible groups.^[9] Regions with elevated gallstone disease, including parts of Europe and North America, report higher case volumes, and recent data through 2025 indicate stable incidence overall but rising absolute cases linked to demographic aging.^[7]^[10]

Historical context

The recognition of ascending cholangitis as a distinct clinical entity began in the 19th century, with early descriptions linking biliary obstruction to infectious processes. In 1877, French neurologist Jean-Martin Charcot, working at the Salpêtrière Hospital in Paris, first detailed the condition as "hepatic fever," reporting cases where jaundice, fever, and abdominal pain arose from biliary tract obstruction complicated by infection.^[11] This seminal work established the classic clinical triad—now eponymously named Charcot's triad—that characterizes the syndrome, emphasizing the role of stasis in predisposing the biliary tree to bacterial invasion.^[12] The terminology evolved over time to reflect growing insights into its pathophysiology. Initially termed simply "cholangitis" to denote bile duct inflammation, the prefix "ascending" gained prominence in the early 20th century to underscore the mechanism of bacterial ascent from the duodenum into the biliary system, often facilitated by obstruction.^[9] This shift highlighted the enteric origin of pathogens, distinguishing it from other forms of biliary inflammation. By the mid-20th century, particularly in the 1950s, medical literature increasingly associated the condition with gallstones as the primary obstructive cause, building on improved surgical and pathological examinations that revealed choledocholithiasis in a majority of cases.^[1] Key milestones further refined understanding and management. The Tokyo Guidelines, initially published in 2007 and updated in 2013 (TG13) and 2018 (TG18), represented pivotal advancements, providing evidence-based frameworks for diagnosing acute cholangitis through structured criteria incorporating clinical, laboratory, and imaging features, which standardized global approaches and improved outcomes.^[13] Historically, treatments prior to 2025 relied heavily on supportive measures and invasive interventions; early 20th-century approaches centered on surgical drainage, such as cholecystectomy or common bile duct exploration, which carried high mortality due to sepsis risks.^[14] The introduction of antibiotics in the 1940s and 1950s marked a turning point by targeting bacterial pathogens like Escherichia coli, while the 1970s advent of endoscopic sphincterotomy revolutionized care, enabling less invasive biliary decompression and reducing the need for open surgery.^[14]

Etiology and pathogenesis

Causes and risk factors

Ascending cholangitis is primarily caused by bacterial infection secondary to biliary obstruction, with choledocholithiasis (common bile duct stones) being the most frequent etiology, accounting for 28 to 70% of cases.^[15]^[16] This obstruction impedes bile flow, allowing enteric bacteria to ascend from the duodenum into the biliary tract.^[5] Other obstructive causes include biliary strictures, often resulting from malignancies such as cholangiocarcinoma or from chronic conditions like pancreatitis, as well as parasitic infestations (e.g., Ascaris lumbricoides in endemic regions) and iatrogenic factors like incomplete stent placement or bacterial introduction during endoscopic retrograde cholangiopancreatography (ERCP).^[1]^[15] These account for 15 to 72% of cases, varying by region and population, with higher rates of malignancy and parasitic causes in certain areas such as Asia.^[15] Key risk factors predisposing individuals to ascending cholangitis include middle to advanced age (typically 50 to 60 years or older), obesity (BMI >30 kg/m²), history of prior cholecystectomy, immunosuppression (e.g., from chemotherapy or HIV), and chronic biliary disorders such as primary sclerosing cholangitis.^[15]^[5] These factors increase the likelihood of gallstone formation or biliary stasis, heightening susceptibility to obstruction and subsequent infection. Hospitalizations for choledocholithiasis and cholangitis have been increasing, reflecting a growing burden of gallstone disease.^[1]^[7] In rare instances, non-obstructive ascending cholangitis may arise from bacterial translocation across the intestinal mucosa in critically ill patients, without identifiable biliary blockage.^[15]

Pathophysiological mechanisms

Ascending cholangitis develops through a sequence of events initiated by biliary obstruction, which induces stasis and elevates intraductal pressure, typically exceeding 20 cm H₂O, thereby compromising the barrier function of the biliary epithelium.^[17] This pressure increase facilitates the reflux of enteric bacteria from the duodenum into the biliary tree, often due to transient incompetence of the sphincter of Oddi, allowing pathogens such as Escherichia coli and Klebsiella species to ascend and colonize the bile ducts.^[1] Bile stasis further promotes bacterial overgrowth by creating an anaerobic environment conducive to proliferation and biofilm formation on ductal surfaces, enhancing adherence and persistence of infection.^[18] The entry of bacteria triggers an inflammatory cascade characterized by the release of endotoxins from gram-negative organisms, which stimulate the biliary mucosa to produce proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6.^[17] This local response escalates to acute cholangitis, with heightened intraductal pressure enhancing vascular permeability and promoting cholangio-venous reflux of infected bile into the hepatic circulation, potentially leading to bacteremia and systemic sepsis.^[18] The resulting endotoxemia amplifies the inflammatory milieu, contributing to widespread endothelial activation and coagulation disturbances.^[1] As the condition progresses, sustained biliary hypertension and unchecked bacterial invasion cause parenchymal liver damage through ischemic injury and direct toxic effects, culminating in cholangiolysis—the enzymatic degradation of bile ductules—and the formation of intrahepatic abscesses.^[17] These pathways underscore the critical interplay between mechanical obstruction, microbial proliferation, and immune-mediated amplification in driving the severity of ascending cholangitis.^[18]

Clinical features

Signs and symptoms

Ascending cholangitis typically presents with a classic triad of symptoms known as Charcot's triad, consisting of right upper quadrant abdominal pain, fever with chills, and jaundice, which is observed in approximately 15-40% of cases according to recent studies, lower than earlier estimates of 50-70%.^[19]^[1] The abdominal pain is often colicky and may radiate to the back or shoulder, while the fever can be high-grade and accompanied by rigors.^[1] Jaundice results from biliary obstruction leading to bilirubin elevation, manifesting as yellowing of the skin and sclera.^[20] Patients may also experience additional symptoms such as nausea, vomiting, lethargy, and, in severe cases, altered mental status due to systemic effects of infection. In severe cases, the addition of hypotension and altered mental status to Charcot's triad forms Reynolds' pentad, observed in 10-20% of patients and indicating septic shock.^[2] These features can vary in intensity but commonly contribute to overall malaise and discomfort.^[20] On physical examination, right upper quadrant abdominal tenderness is a prominent finding.^[1] Signs of dehydration, such as dry mucous membranes, or shock, including hypotension and tachycardia, may be evident in more advanced presentations.^[20] Symptom presentation can differ based on the degree of biliary obstruction; partial obstruction often leads to intermittent or recurrent symptoms, whereas complete blockage typically causes a more acute onset with rapid progression.^[21]

Severity assessment

Severity assessment of ascending cholangitis, also known as acute cholangitis, relies primarily on the Tokyo Guidelines 2018 (TG18), which classify the condition into three grades to guide therapeutic decisions and predict outcomes.^[4] Grade I (mild) is defined as acute cholangitis with systemic inflammation but without organ dysfunction or the need for urgent biliary drainage, typically managed with antibiotics and supportive care alone.^[4] Grade II (moderate) involves the presence of at least two clinical predictors of severity, including leukocytosis (>12,000/μL) or leukopenia (<4,000/μL), high fever (≥39°C), age ≥75 years, hyperbilirubinemia (>5 mg/dL), or hypoalbuminemia (<25 g/L or <0.7 times the lower limit of normal).^[4] These predictors indicate a higher risk of complications, necessitating early biliary decompression in addition to medical therapy.^[4] Grade III (severe) acute cholangitis is characterized by organ dysfunction in at least one system, such as cardiovascular (hypotension requiring dopamine ≥5 μg/kg/min or norepinephrine), neurological (disturbed consciousness with Glasgow Coma Scale <15), respiratory (PaO₂/FiO₂ ratio <300), renal (serum creatinine ≥2.0 mg/dL or oliguria), hepatic (PT-INR ≥1.5), or hematological (platelet count <100,000/μL).^[4] This grade demands intensive care, including hemodynamic stabilization and emergent biliary drainage once the patient is stable.^[4] Key clinical predictors like advanced age (>75 years), hyperbilirubinemia (>5 mg/dL), and hypoalbuminemia further stratify risk within these grades, with older patients showing heightened vulnerability to progression.^[13] The TG18 severity grading also serves as a prognostic tool, incorporating components of inflammation (e.g., fever and leukocytosis), cholestasis (e.g., bilirubin levels), and organ dysfunction to enable risk stratification and timely intervention.^[4] As of 2025, no major revisions to the TG18 severity criteria have been issued, though recent studies emphasize prompt application of these scores in elderly patients to improve outcomes, given their inclusion as a core predictor.^[22]

Diagnosis

Laboratory tests

Laboratory investigations play a crucial role in supporting the diagnosis of ascending cholangitis by demonstrating evidence of infection, cholestasis, and potential organ dysfunction. Initial blood tests typically include a complete blood count, liver function tests, inflammatory markers, blood cultures, coagulation studies, and renal function assessment. Inflammatory markers often reveal leukocytosis, with white blood cell counts exceeding 10,000/μL in most cases, reflecting the systemic inflammatory response to biliary infection. C-reactive protein levels are commonly elevated above 1 mg/dL, serving as a sensitive indicator of inflammation. Procalcitonin levels may be measured to help assess severity, as elevated concentrations are associated with severe bacterial infections in the biliary tree.^[4] Liver function tests characteristically show a cholestatic pattern, with total bilirubin levels ≥2 mg/dL indicating obstructive jaundice. Alkaline phosphatase is markedly elevated, often more than twice the upper limit of normal, due to biliary obstruction. Transaminases, such as alanine and aspartate aminotransferases, exhibit only mild elevations, distinguishing cholangitis from hepatocellular injury. Blood cultures are positive in 20-70% of cases, identifying common pathogens like Escherichia coli and Klebsiella species that ascend from the gut. This finding contributes to the evidence of inflammatory response in diagnostic frameworks such as the Tokyo Guidelines. Coagulation studies may show prolonged prothrombin time or international normalized ratio (PT/INR >1.5) in severe cases, reflecting hepatic dysfunction or disseminated intravascular coagulation. Renal function tests can demonstrate elevated serum creatinine levels (>2 mg/dL) in patients with associated sepsis, indicating acute kidney injury.

Imaging studies

Ultrasound serves as the initial imaging modality of choice for suspected ascending cholangitis due to its non-invasive nature, wide availability, lack of ionizing radiation, and ability to rapidly assess for biliary obstruction. It effectively detects common bile duct (CBD) dilatation, typically defined as a CBD diameter greater than 6 mm in adults, with a sensitivity approaching 99% for identifying ductal dilatation as evidence of obstruction. Additionally, ultrasound can visualize gallstones and intraductal debris, though its sensitivity for detecting CBD stones ranges from 50% to 80%, limited by factors such as bowel gas interference and operator dependence. Thickening of the bile duct walls, a hallmark finding in the appropriate clinical context, further supports the diagnosis.^[23]^[16] In more complex cases or when ultrasound is inconclusive, computed tomography (CT) or magnetic resonance cholangiopancreatography (MRCP) is employed to delineate the etiology and extent of biliary pathology. CT excels in identifying complications such as periductal inflammation, abscesses, strictures, or underlying malignancies, providing comprehensive evaluation of the abdomen and staging potential tumors, though it has lower sensitivity for choledocholithiasis compared to other modalities. MRCP, a non-invasive technique, offers detailed visualization of the biliary tree and is particularly valuable for confirming stones, strictures, or the level of obstruction, with sensitivity exceeding 90% for CBD stones in multiple studies. Its advantages include no radiation exposure and high diagnostic accuracy without the need for contrast agents in stable patients.^[24]^[1]^[25] Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) provide direct visualization of the biliary ducts for diagnostic confirmation in invasive settings. ERCP allows real-time imaging of ductal abnormalities, including stones and strictures, with high diagnostic accuracy, though it carries risks associated with its procedural nature. PTC is reserved for cases where ERCP is not feasible, such as altered anatomy, offering direct duct opacification to identify obstructive lesions. Both modalities enable assessment of infection-related changes like pus or debris within the ducts.^[1] Recent advancements as of 2025 highlight the expanding role of endoscopic ultrasound (EUS) in elderly patients with ascending cholangitis, particularly for detecting small CBD stones missed by transabdominal ultrasound or MRCP, achieving sensitivities of 95% or higher without radiation exposure. EUS provides high-resolution proximity imaging of the biliary system, making it a safer alternative in frail populations prone to procedural complications.^[26]^[10]

Diagnostic criteria

The diagnosis of ascending cholangitis relies on the Tokyo Guidelines 2018 (TG18), which establish a tiered system to confirm the condition based on clinical, laboratory, and imaging evidence. These criteria, current as of 2025, are divided into three parts: Part A assesses systemic inflammation, Part B evaluates cholestasis, and Part C confirms the biliary etiology through imaging.^[4] Part A requires evidence of systemic inflammation, including fever and/or shaking chills, or laboratory indicators such as white blood cell count >10,000/mm³ or <4,000/mm³, or C-reactive protein level of at least 1 mg/dL.^[4] Part B involves signs of cholestasis, such as jaundice with total bilirubin ≥2 mg/dL (≥34.2 μmol/L) or abnormal liver function tests including alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase, or alanine aminotransferase elevated to at least 1.5 times the upper limit of normal.^[4] Part C mandates imaging findings like biliary dilatation or direct evidence of the underlying cause, such as a stone, stricture, or stent in the bile duct.^[4] A suspected diagnosis is made when one item from Part A and one from Part B are present, prompting urgent evaluation.^[4] A definite diagnosis requires fulfillment of one item from each part (A + B + C), providing high diagnostic accuracy. Validation studies report varying sensitivity and specificity, such as 86% sensitivity and 63% specificity in one post-ERCP cohort.^[27] Differential diagnosis considerations include acute cholecystitis, which typically presents with right upper quadrant pain and fever but lacks prominent jaundice and biliary dilatation on imaging, and acute pancreatitis, characterized by epigastric pain radiating to the back with elevated amylase/lipase but without cholestatic liver enzyme patterns.^[1] Procalcitonin has been studied for predicting severity in acute cholangitis, with elevated levels (cut-offs around 1-3 ng/mL) associated with severe cases and need for urgent decompression, but it is not part of the diagnostic criteria.^[28]

Management

Initial medical therapy

The initial medical therapy for ascending cholangitis focuses on rapid stabilization of the patient through fluid resuscitation, empiric antimicrobial administration, and supportive measures to address systemic inflammation and infection, particularly in those with hemodynamic instability or sepsis.^[1] This approach is guided by severity assessment, with more aggressive interventions for severe cases involving organ dysfunction.^[29] Fluid resuscitation is a cornerstone of initial management, involving aggressive intravenous administration of crystalloid solutions such as normal saline or lactated Ringer's to correct hypotension and hypovolemia, targeting a mean arterial pressure greater than 65 mmHg in hypotensive patients.^[1] Electrolyte imbalances, common due to fever and gastrointestinal losses, should be monitored and corrected concurrently with cardiac monitoring and pulse oximetry to ensure adequate circulation.^[30] Empiric broad-spectrum intravenous antibiotics are initiated immediately upon suspicion of ascending cholangitis to cover common enteric pathogens, including gram-negative bacilli like Escherichia coli and Klebsiella species, as well as enterococci and anaerobes.^[1] Preferred regimens include piperacillin-tazobactam (4.5 g every 6 hours) as first-line therapy, or alternatives such as a carbapenem (e.g., meropenem) in regions with high extended-spectrum beta-lactamase prevalence, or ciprofloxacin plus metronidazole for penicillin-allergic patients.^[30] Therapy should be de-escalated based on blood and biliary culture results, typically within 48-72 hours, to narrow coverage and minimize resistance.^[1] For mild cases without complications, the duration is generally 4-7 days following clinical improvement, though recent evidence supports shorter courses (e.g., 3-5 days) in rapid responders per updates to the Tokyo Guidelines 2018 antimicrobial recommendations.^[29]^[31] Supportive care includes analgesia with opioids for abdominal pain, antiemetics such as ondansetron for nausea, and close monitoring of vital signs and organ function.^[1] Patients with severe disease, characterized by altered mental status or shock, require intensive care unit admission for advanced hemodynamic support, including vasopressors if fluid resuscitation alone is insufficient.^[30]

Biliary decompression

Biliary decompression is essential for resolving the obstruction that perpetuates infection in ascending cholangitis, with endoscopic retrograde cholangiopancreatography (ERCP) serving as the preferred initial method due to its efficacy in achieving drainage and addressing the underlying cause.^[32] During ERCP, endoscopic sphincterotomy is typically performed to facilitate access, followed by stone extraction if choledocholithiasis is present or placement of a biliary stent to restore flow.^[13] This approach yields technical success rates exceeding 90% in most cases, particularly when performed by experienced endoscopists.^[33] According to the Tokyo Guidelines 2018 (TG18), timing of decompression is guided by disease severity: urgent intervention is recommended for severe cases (grade III) once the patient is stabilized, while early drainage within 24 to 48 hours is advised for moderate cases (grade II) alongside supportive care.^[13] Delaying beyond this window in moderate or severe cholangitis increases risks of complications and mortality.^[34] When ERCP is unsuccessful or contraindicated, such as in patients with altered anatomy or hemodynamic instability, percutaneous transhepatic cholangiography (PTC) with biliary drainage is employed as an alternative to provide external or internal-external decompression.^[35] PTC involves ultrasound- or fluoroscopy-guided needle access to the biliary tree for catheter placement, offering reliable relief in up to 95% of suitable candidates and serving as a bridge to definitive therapy.^[36] Recent advancements as of 2024-2025 have emphasized the use of covered self-expandable metal stents (SEMS) during ERCP or PTC for malignant biliary obstructions complicating cholangitis, demonstrating prolonged patency compared to uncovered stents due to minimized tumor ingrowth.^[37]^[38] These fully covered designs, often with anti-migration features, have improved clinical outcomes in inoperable cases by enhancing drainage durability and quality of life.^[38]

Surgical options

Surgical interventions for ascending cholangitis are typically reserved for definitive management of underlying causes after initial biliary decompression, particularly in cases where endoscopic approaches fail or are not feasible.^[14] These procedures aim to address obstructions such as gallstones, strictures, or tumors, thereby preventing recurrence.^[15] Cholecystectomy is the standard surgical option for gallstone-related ascending cholangitis, performed after resolution of the acute infection to reduce the risk of recurrent episodes.^[39] Laparoscopic cholecystectomy is preferred due to its minimally invasive nature, lower complication rates, and shorter recovery time compared to open surgery. Early or index admission cholecystectomy, within the same hospitalization as the acute event, has been shown to be safe and associated with decreased readmission rates and morbidity, without increased risk of complications.^[40] For cases involving bile duct strictures, tumors, or failed endoscopic stone extraction, choledochotomy—surgical exploration and incision of the common bile duct—or biliary reconstruction procedures such as Roux-en-Y hepaticojejunostomy are indicated.^[15] These interventions, often performed via open surgery, allow for direct stone removal, T-tube placement for drainage, or bypass of obstructions, and are particularly necessary in recurrent cholangitis or concomitant pathologies like acute cholecystitis.^[14] However, emergency surgical decompression carries higher mortality rates (20-60%) and morbidity compared to endoscopic methods, underscoring its role as a salvage option.^[14] Indications for surgery include persistent obstruction despite endoscopic or percutaneous drainage, multiple recurrent episodes, or underlying malignancy requiring resection.^[15] Biliary drainage serves as a bridge to these elective or urgent procedures in hemodynamically stable patients.^[14] As of 2025, robotic-assisted approaches, such as robotic common bile duct exploration (RACBDE), are increasingly utilized for complex cases, including in elderly patients with choledocholithiasis contributing to cholangitis.^[41] These techniques offer enhanced precision, reduced conversion to open surgery, and improved outcomes in minimally invasive stone clearance, though they remain more costly than standard laparoscopy.^[41]

Complications and prognosis

Acute complications

Ascending cholangitis, if untreated or inadequately managed, can rapidly progress to biliary sepsis, characterized by systemic dissemination of biliary tract pathogens leading to bacteremia in 25-40% of cases.^[5] This bacteremia often escalates to septic shock, a life-threatening condition involving profound hypotension and tissue hypoperfusion, with mortality rates reaching 10-30% in instances of delayed biliary drainage.^[5] Septic shock in this context stems from the overwhelming inflammatory response to ascending bacterial infection, primarily involving gram-negative organisms such as Escherichia coli.^[1] Beyond sepsis, acute complications include the formation of hepatic abscesses, which arise from direct extension of infection into the liver parenchyma and can lead to further systemic spread if ruptured.^[1] Multi-organ failure frequently complicates severe cases, manifesting as hepatic dysfunction, respiratory distress, and cardiovascular collapse due to the cascading effects of endotoxemia.^[5] Acute kidney injury is another critical sequela, often resulting from hypotension-induced hypoperfusion or direct nephrotoxic effects of bacterial toxins, exacerbating overall morbidity and mortality.^[5] Key risk factors for these acute complications include delayed biliary decompression beyond 48 hours, which significantly heightens the likelihood of progression to septic shock and organ failure.^[42] Elderly patients face elevated risks due to diminished physiological reserve and higher prevalence of immunosuppression.^[1] Comorbidities such as diabetes, malignancy, or pre-existing renal disease further compound vulnerability by impairing immune response and biliary clearance mechanisms.^[5] Prompt source control through biliary drainage remains essential to mitigate these complications, as it interrupts the infectious nidus and halts sepsis progression, reducing overall mortality to less than 10% with timely intervention.^[1]

Long-term outcomes

With timely treatment, including antibiotics and biliary decompression, the overall mortality rate for ascending cholangitis (also known as acute cholangitis) is approximately 5-10%.^[5] In severe untreated cases, however, mortality can escalate to up to 50%, primarily due to progression to septic shock and multiorgan failure.^[43] Key prognostic factors include the timing of intervention; early biliary drainage within 24-48 hours significantly improves survival by reducing persistent organ failure and shortening hospital stays.^[44] Without addressing underlying causes such as biliary stones or strictures, the risk of recurrence ranges from 10-30% within the first few years following an initial episode.^[45] Long-term sequelae may include the development of chronic or recurrent pyogenic cholangitis, characterized by repeated infections and biliary obstruction.^[46] In patients with frequent recurrences, progressive hepatic parenchymal damage can lead to liver cirrhosis and portal hypertension.^[47] Additionally, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, a potential complication of drainage procedures, occurs in about 5% of cases and may contribute to chronic pancreatic insufficiency in severe instances.^[48] As of 2025, adherence to updated guidelines, such as the Tokyo Guidelines, has led to improved long-term outcomes in resource-rich settings, with reduced recurrence and mortality through multidisciplinary care and timely access to advanced interventions.^[49]

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a game-changer for acute cholangitis patients in a resource-limited ...
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