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Ascending cholangitis
Ascending cholangitis
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Ascending cholangitis
Other namesacute cholangitis, cholangitis
Duodenoscopy image of pus extruding from the ampulla of Vater, indicative of cholangitis
SpecialtyGastroenterology
General surgery
Symptomsjaundice, fever and abdominal pain

Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct, usually caused by bacteria ascending from its junction with the duodenum (first part of the small intestine). It tends to occur if the bile duct is already partially obstructed by gallstones.[1][2]

Cholangitis can be life-threatening, and is regarded as a medical emergency.[1] Characteristic symptoms include yellow discoloration of the skin or whites of the eyes, fever, abdominal pain, and in severe cases, low blood pressure and confusion. Initial treatment is with intravenous fluids and antibiotics, but there is often an underlying problem (such as gallstones or narrowing in the bile duct) for which further tests and treatments may be necessary, usually in the form of endoscopy to relieve obstruction of the bile duct.[1][3] The word is from Greek chol-, bile + ang-, vessel + -itis, inflammation.

Signs and symptoms

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Charcot's triad

A person with cholangitis may complain of abdominal pain (particularly in the right upper quadrant of the abdomen), fever, rigors (uncontrollable shaking) and a feeling of uneasiness (malaise). Some may report jaundice (yellow discoloration of the skin and the whites of the eyes).[1]

Physical examination findings typically include jaundice and right upper quadrant tenderness.[1] Charcot's triad is a set of three common findings in cholangitis: abdominal pain, jaundice, and fever.[4] This was assumed in the past to be present in 50–70% of cases, although more recently the frequency has been reported as 15–20%.[1] Reynolds' pentad includes the findings of Charcot's triad with the presence of septic shock and mental confusion.[5] This combination of symptoms indicates worsening of the condition and the development of sepsis, and is seen less commonly still.[1][2]

In the elderly, the presentation may be atypical; they may directly collapse due to sepsis without first showing typical features.[2] Those with an indwelling stent in the bile duct (see below) may not develop jaundice.[2]

Causes

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Bile duct obstruction, which is usually present in acute cholangitis, is generally due to gallstones. 10–30% of cases, however, are due to other causes such as benign stricturing (narrowing of the bile duct without an underlying tumor), postoperative damage or an altered structure of the bile ducts such as narrowing at the site of an anastomosis (surgical connection), various tumors (cancer of the bile duct, gallbladder cancer, cancer of the ampulla of Vater, pancreatic cancer, cancer of the duodenum), anaerobic organisms such as Clostridium and Bacteroides (especially in the elderly and those who have undergone previous surgery of the biliary system).[1]

Parasites which may infect the liver and bile ducts may cause cholangitis; these include the roundworm Ascaris lumbricoides and the liver flukes Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus.[6] In people with AIDS, a large number of opportunistic organisms has been known to cause AIDS cholangiopathy, but the risk has rapidly diminished since the introduction of effective AIDS treatment.[1][7] Cholangitis may also complicate medical procedures involving the bile duct, especially ERCP. To prevent this, it is recommended that those undergoing ERCP for any indication receive prophylactic (preventative) antibiotics.[3][8]

The presence of a permanent biliary stent (e.g. in pancreatic cancer) slightly increases the risk of cholangitis, but stents of this type are often needed to keep the bile duct patent under outside pressure.[1]

Pathogenesis

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Diagram showing liver and related parts of the digestive system

Bile is produced by the liver, and serves to eliminate cholesterol and bilirubin from the body, as well as emulsifying of fats to make them more soluble in water and aid in their digestion. Bile is formed in the liver by hepatocytes (liver cells) and excreted into the common hepatic duct. Part of the bile is stored in the gall bladder because of back pressure (exerted by the sphincter of Oddi), and may be released at the time of digestion. The gallbladder also concentrates the bile by absorbing water and dissolved salts from it. All bile reaches the duodenum (first part of the small intestine) through the common bile duct and the ampulla of Vater. The sphincter of Oddi, located at the junction of the ampulla of Vater and the duodenum, is a circular muscle that controls the release of both bile and pancreatic secretions into the digestive tract.[1]

The biliary tree is normally relatively free of bacteria because of certain protective mechanisms. The sphincter of Oddi acts as a mechanical barrier. The biliary system normally has low pressure (8 to 12 cmH2O)[9] and allows bile to flow freely through. The continuous forward flow of the bile in the duct flushes bacteria, if present, into the duodenum, and does not allow the establishment of an infection. The constitution of bile—bile salts[1] and immunoglobulin[2] secreted by the epithelium of the bile duct also has a protective role.

Bacterial contamination alone in absence of obstruction does not usually result in cholangitis.[2] However increased pressure within the biliary system (above 20 cmH2O)[10] resulting from obstruction in the bile duct widens spaces between the cells lining the duct, bringing bacterially contaminated bile in contact with the blood stream. It also adversely affects the function of Kupffer cells, which are specialized macrophage cells that assist in preventing bacteria from entering the biliary system. Finally, increased biliary pressure decreases production of IgA immunoglobulins in the bile.[11] This results in bacteremia (bacteria in the blood stream) and gives rise to the systemic inflammatory response syndrome (SIRS) comprising fever (often with rigors), tachycardia, increased respiratory rate and increased white blood cell count; SIRS in the presence of suspected or confirmed infection is called sepsis.[1] Biliary obstruction itself disadvantages the immune system and impairs its capability to fight infection, by impairing the function of certain immune system cells (neutrophil granulocytes) and modifying the levels of immune hormones (cytokines).[1]

In ascending cholangitis, it is assumed that organisms migrate backwards up the bile duct as a result of partial obstruction and decreased function of the sphincter of Oddi.[1] Other theories about the origin of the bacteria, such as through the portal vein or transmigration from the colon, are considered less likely.[1]

Diagnosis

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Blood tests

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Routine blood tests show features of acute inflammation (raised white blood cell count and elevated C-reactive protein level), and usually abnormal liver function tests (LFTs). In most cases the LFTs will be consistent with obstruction: raised bilirubin, alkaline phosphatase and γ-glutamyl transpeptidase. In the early stages, however, pressure on the liver cells may be the main feature and the tests will resemble those in hepatitis, with elevations in alanine transaminase and aspartate transaminase.[1]

Blood cultures are often performed in people with fever and evidence of acute infection. These yield the bacteria causing the infection in 36% of cases,[12] usually after 24–48 hours of incubation. Bile, too, may be sent for culture during ERCP (see below). The most common bacteria linked to ascending cholangitis are gram-negative bacilli: Escherichia coli (25–50%), Klebsiella (15–20%) and Enterobacter (5–10%). Of the gram-positive cocci, Enterococcus causes 10–20%.[13]

Medical imaging

[edit]
Cholangiogram through a nasobiliary drain showing the common bile duct in black (diagonally from top left to bottom right in the center) with an interruption in the contour due to a large gallstone.

Given that ascending cholangitis usually occurs in the setting of bile duct obstruction, various forms of medical imaging may be employed to identify the site and nature of this obstruction. The first investigation is usually ultrasound, as this is the most easily available.[1] Ultrasound may show dilation of the bile duct and identifies 38% of bile duct stones; it is relatively poor at identifying stones farther down the bile duct. Ultrasound can help distinguish between cholangitis and cholecystitis (inflammation of the gallbladder), which has similar symptoms to cholangitis but appears differently on ultrasound.[14] A better test is magnetic resonance cholangiopancreatography (MRCP), which uses magnetic resonance imaging (MRI); this has a comparable sensitivity to ERCP.[14] Smaller stones, however, can still be missed on MRCP depending on the quality of the hospital's facilities.[1]

The gold standard test for biliary obstruction is still endoscopic retrograde cholangiopancreatography (ERCP). This involves the use of endoscopy (passing a tube through the mouth into the esophagus, stomach and thence to the duodenum) to pass a small cannula into the bile duct. At that point, radiocontrast is injected to opacify the duct, and X-rays are taken to get a visual impression of the biliary system. On the endoscopic image of the ampulla, one can sometimes see a protuberant ampulla from an impacted gallstone in the common bile duct or the frank extrusion of pus from the common bile duct orifice. On the X-ray images (known as cholangiograms), gallstones are visible as non-opacified areas in the contour of the duct. For diagnostic purposes, ERCP has now generally been replaced by MRCP. ERCP is only used first-line in critically ill patients in whom delay for diagnostic tests is not acceptable; however, if the index of suspicion for cholangitis is high, an ERCP is typically done to achieve drainage of the obstructed common bile duct.[1]

If other causes rather than gallstones are suspected (such as a tumor), computed tomography and endoscopic ultrasound (EUS) may be performed to identify the nature of the obstruction. EUS may be used to obtain biopsy (tissue sample) of suspicious masses.[1] EUS may also replace diagnostic ERCP for stone disease, although this depends on local availability.[3]

Treatment

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Fluids and antibiotics

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Cholangitis requires admission to hospital. Intravenous fluids are administered, especially if the blood pressure is low, and antibiotics are commenced. Empirical treatment with broad-spectrum antibiotics is usually necessary until it is known for certain which pathogen is causing the infection, and to which antibiotics it is sensitive. Combinations of penicillins and aminoglycosides are widely used, although ciprofloxacin has been shown to be effective in most cases, and may be preferred to aminoglycosides because of fewer side effects. Metronidazole is often added to specifically treat the anaerobic pathogens, especially in those who are very ill or at risk of anaerobic infections. Antibiotics are continued for 7–10 days.[1] Drugs that increase the blood pressure (vasopressors) may also be required to counter the low blood pressure.[2]

Endoscopy

[edit]

The definitive treatment for cholangitis is relief of the underlying biliary obstruction.[1] This is usually deferred until 24–48 hours after admission, when the patient is stable and has shown some improvement with antibiotics, but may need to happen as an emergency in case of ongoing deterioration despite adequate treatment,[1] or if antibiotics are not effective in reducing the signs of infection (which happens in 15% of cases).[2][3]

Endoscopic retrograde cholangiopancreatography (ERCP) is the most common approach in unblocking the bile duct. This involves endoscopy (passing a fiberoptic tube through the stomach into the duodenum), identification of the ampulla of Vater and insertion of a small tube into the bile duct. A sphincterotomy (making a cut in the sphincter of Oddi) is typically done to ease the flow of bile from the duct and to allow insertion of instruments to extract gallstones that are obstructing the common bile duct; alternatively or additionally, the common bile duct orifice can be dilated with a balloon.[15] Stones may be removed either by direct suction or by using various instruments, including balloons and baskets to trawl the bile duct in order to pull stones into the duodenum. Obstructions that are caused by larger stones may require the use of an instrument known as a mechanical lithotriptor in order to crush the stone prior to removal.[16] Obstructing stones that are too large to be removed or broken mechanically by ERCP may be managed by extracorporeal shock wave lithotripsy. This technique uses acoustic shock waves administered outside the body to break down the stones.[17] An alternative technique to remove very large obstructing stones is electrohydraulic lithotripsy, where a small endoscope known as a cholangioscope is inserted by ERCP to directly visualize the stone. A probe uses electricity to generate shock waves that break down the obstructing stone.[18] Rarely, surgical exploration of the common bile duct (termed choledochotomy), which can be performed with laparoscopy, is required to remove the stone.[19]

Narrowed areas may be bridged by a stent, a hollow tube that keeps the duct open. Removable plastic stents are used in uncomplicated gallstone disease, while permanent self-expanding metal stents with a longer lifespan are used if the obstruction is due to pressure from a tumor such as pancreatic cancer. A nasobiliary drain may be left behind; this is a plastic tube that passes from the bile duct through the stomach and the nose and allows continuous drainage of bile into a receptible. It is similar to a nasogastric tube, but passes into the common bile duct directly, and allows for serial x-ray cholangiograms to be done to identify the improvement of the obstruction. The decision on which of the aforementioned treatments to apply is generally based on the severity of the obstruction, findings on other imaging studies, and whether the patient has improved with antibiotic treatment.[1] Certain treatments may be unsafe if blood clotting is impaired, as the risk of bleeding (especially from sphincterotomy) is increased in the use of medication such as clopidogrel (which inhibits platelet aggregation) or if the prothrombin time is significantly prolonged. For a prolonged prothrombin time, vitamin K or fresh frozen plasma may be administered to reduce bleeding risk.[1]

Percutaneous biliary drainage

[edit]

In cases where a person is too ill to tolerate endoscopy or when a retrograde endoscopic approach fails to access the obstruction, a percutaneous transhepatic cholangiogram (PTC) may be performed to evaluate the biliary system for placement of a percutaneous biliary drain (PBD).[20][3] This is often necessary in the case of a proximal stricture or a bilioenteric anastomosis (a surgical connection between the bile duct and small bowel, such as the duodenum or jejunum).[2] Once access across the stricture is obtained, balloon dilation can be performed and stones can be swept forward into the duodenum.[20] Due to potential complications of percutaneous biliary drain placement and the necessity of regular drain maintenance,[2] a retrograde approach via ERCP remains first-line therapy.[1]

Cholecystectomy

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Not all gallstones implicated in ascending cholangitis actually originate from the gallbladder, but cholecystectomy (surgical removal of the gallbladder) is generally recommended in people who have been treated for cholangitis due to gallstone disease. This is typically delayed until all symptoms have resolved and ERCP or MRCP have confirmed that the bile duct is clear of gallstones.[1][2][3] Those who do not undergo cholecystectomy have an increased risk of recurrent biliary pain, jaundice, further episodes of cholangitis, and need for further ERCP or cholecystostomy; the risk of death is also significantly increased.[21]

Biliary sepsis

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Biliary sepsis is a systemic complication of acute cholangitis that occurs when infection spreads from the bile ducts into the bloodstream.

A systemic infection resulting from bacterial translocation from the biliary tract, most commonly due to acute cholangitis or suppurative cholecystitis. It is a life-threatening complication of biliary obstruction (e.g., choledocholithiasis, strictures) and requires urgent intervention.[22]

Prognosis

[edit]

Acute cholangitis carries a significant risk of death, the leading cause being irreversible shock with multiple organ failure (a possible complication of severe infections).[7] Improvements in diagnosis and treatment have led to a reduction in mortality: before 1980, the mortality rate was greater than 50%, but after 1980 it was 10–30%.[7] Patients with signs of multiple organ failure are likely to die unless they undergo early biliary drainage and treatment with systemic antibiotics. Other causes of death following severe cholangitis include heart failure and pneumonia.[23]

Risk factors indicating an increased risk of death include older age, female gender, a history of liver cirrhosis, biliary narrowing due to cancer, acute kidney injury and the presence of liver abscesses.[24] Complications following severe cholangitis include kidney failure, respiratory failure (inability of the respiratory system to oxygenate blood and/or eliminate carbon dioxide), abnormal heart rhythms, wound infection, pneumonia, gastrointestinal bleeding and myocardial ischemia (lack of blood flow to the heart, leading to heart attacks).[23]

Epidemiology

[edit]

In the Western world, about 15% of all people have gallstones in their gallbladder but the majority are unaware of this and have no symptoms. Over ten years, 15–26% will have one or more episodes of biliary colic (abdominal pain due to the passage of gallstones through the bile duct into the digestive tract), and 2–3% will develop complications of obstruction: acute pancreatitis, cholecystitis or acute cholangitis.[3] Prevalence of gallstone disease increases with age and body mass index (a marker of obesity). However, the risk is also increased in those who lose weight rapidly (e.g. after weight loss surgery) due to alterations in the composition of the bile that makes it prone to form stones. Gallstones are slightly more common in women than in men, and pregnancy increases the risk further.[25]

History

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Dr Jean-Martin Charcot, working at the Salpêtrière Hospital in Paris, France, is credited with early reports of cholangitis, as well as his eponymous triad, in 1877.[4] He referred to the condition as "hepatic fever" (fièvre hépatique).[4][7] Dr Benedict M. Reynolds, an American surgeon, reignited interest in the condition in his 1959 report with colleague Dr Everett L. Dargan, and formulated the pentad that carries his name.[5] It remained a condition generally treated by surgeons, with exploration of the bile duct and excision of gallstones, until the ascendancy of ERCP in 1968.[26] ERCP is generally performed by internal medicine or gastroenterology specialists. In 1992 it was shown that ERCP was generally safer than surgical intervention in ascending cholangitis.[27]

See also

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References

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[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Ascending cholangitis

View on Grokipedia
from Grokipedia
Ascending cholangitis, also known as acute cholangitis, is a potentially life-threatening bacterial of the biliary tree that arises from obstruction of the bile ducts, most commonly due to gallstones (choledocholithiasis). This condition leads to bacterial ascension from the into the biliary system, causing inflammation and possible systemic . 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. The primary etiology involves partial or complete biliary obstruction, which increases intraductal pressure and facilitates bacterial proliferation and translocation into the bloodstream. Common causative pathogens include and species, though other such as Enterococcus and anaerobes can be involved. Beyond gallstones, which account for the majority of cases, contributing factors include benign strictures, malignant tumors (e.g., or ), 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. Risk factors encompass prior biliary interventions, sclerosing cholangitis, infection, and travel to regions with parasitic endemicity. 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. Fever occurs in about 90% of patients, often accompanied by chills, while jaundice and pain are present in 60% to 70%. In severe cases, Reynolds' pentad, which adds hypotension and altered mental status indicative of septic shock, is rarely observed (less than 5%). Additional symptoms may include nausea, vomiting, dark urine, and pale stools due to cholestasis. Without prompt intervention, complications such as hepatic abscesses, multiorgan failure, or overwhelming sepsis can develop. 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 (e.g., fever >38°C or ), cholestasis (e.g., total ≥2 mg/dL), and biliary dilatation or evidence of on imaging. Laboratory tests typically reveal , elevated liver enzymes (e.g., , gamma-glutamyl transferase), hyperbilirubinemia, and positive blood cultures in 20% to 70% of cases. Imaging modalities include abdominal ultrasound (first-line for detecting dilatation or stones), (MRCP) for detailed anatomy, or ERCP for both and therapeutic intervention. Management prioritizes rapid , antibiotics, and biliary decompression to prevent mortality, which exceeds 50% without drainage but drops below 10% with timely treatment. Initial 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. Biliary drainage via ERCP is the gold standard, achieving success in 94% to 98% of procedures, with as an alternative for failed ERCP. In mild cases, drainage can be delayed 24 to 48 hours, but urgent intervention is required for moderate to severe presentations. Long-term prognosis is favorable with early intervention, though recurrent episodes may necessitate or addressing underlying strictures.

Background

Definition and epidemiology

Ascending cholangitis, also known as acute cholangitis, is a life-threatening bacterial infection of the that occurs when obstruction allows bacteria to ascend retrogradely from the into the bile ducts. This condition typically arises in the context of biliary obstruction, most commonly due to choledocholithiasis, leading to and potential systemic complications if untreated. Epidemiologically, ascending cholangitis is relatively uncommon, with an incidence of 0.3% to 1.6% among patients hospitalized for gallstone disease. In the , analyses estimate approximately 10,000 to 50,000 cases annually, though rates per 100,000 admissions have shown a slight increase, from approximately 30 in 2005 to higher figures in recent years. Globally, incidence rates are comparable, with a study in the estimating 28 cases per 100,000 individuals annually. 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 prevalence in aging populations. There is no significant gender disparity, with males and females affected equally, though associations exist with comorbidities such as and prior biliary interventions that elevate risk in susceptible groups. Regions with elevated disease, including parts of and , report higher case volumes, and recent data through 2025 indicate stable incidence overall but rising absolute cases linked to demographic aging.

Historical context

The recognition of ascending cholangitis as a distinct clinical entity began in the , with early descriptions linking biliary obstruction to infectious processes. In 1877, French neurologist , working at the Salpêtrière Hospital in , first detailed the condition as "hepatic fever," reporting cases where , fever, and arose from biliary tract obstruction complicated by . 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. The terminology evolved over time to reflect growing insights into its . Initially termed simply "cholangitis" to denote bile duct , the prefix "ascending" gained prominence in the early to underscore the mechanism of bacterial ascent from the into the biliary system, often facilitated by obstruction. This shift highlighted the enteric origin of pathogens, distinguishing it from other forms of biliary . 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. 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. Historically, treatments prior to 2025 relied heavily on supportive measures and invasive interventions; early 20th-century approaches centered on surgical drainage, such as or exploration, which carried high mortality due to risks. The introduction of antibiotics in the 1940s and 1950s marked a turning point by targeting bacterial pathogens like , while the 1970s advent of endoscopic sphincterotomy revolutionized care, enabling less invasive biliary decompression and reducing the need for open surgery.

Etiology and pathogenesis

Causes and risk factors

Ascending cholangitis is primarily caused by bacterial secondary to biliary obstruction, with choledocholithiasis ( stones) being the most frequent , accounting for 28 to 70% of cases. This obstruction impedes flow, allowing enteric to ascend from the into the . Other obstructive causes include biliary strictures, often resulting from malignancies such as or from chronic conditions like , as well as parasitic infestations (e.g., in endemic regions) and iatrogenic factors like incomplete placement or bacterial introduction during (ERCP). 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 . Key risk factors predisposing individuals to ascending cholangitis include middle to advanced age (typically 50 to 60 years or older), (BMI >30 kg/m²), history of prior , (e.g., from or ), and chronic biliary disorders such as . These factors increase the likelihood of formation or biliary stasis, heightening susceptibility to obstruction and subsequent . Hospitalizations for choledocholithiasis and cholangitis have been increasing, reflecting a growing burden of disease. In rare instances, non-obstructive ascending cholangitis may arise from bacterial translocation across the intestinal mucosa in critically ill patients, without identifiable biliary blockage.

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 of the biliary . This pressure increase facilitates the of enteric from the into the biliary tree, often due to transient incompetence of the , allowing pathogens such as and species to ascend and colonize the ducts. stasis further promotes bacterial overgrowth by creating an anaerobic environment conducive to proliferation and formation on ductal surfaces, enhancing adherence and persistence of infection. The entry of 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. This local response escalates to acute cholangitis, with heightened intraductal pressure enhancing and promoting cholangio-venous reflux of infected into the hepatic circulation, potentially leading to bacteremia and systemic . The resulting endotoxemia amplifies the inflammatory milieu, contributing to widespread endothelial activation and coagulation disturbances. 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. These pathways underscore the critical interplay between mechanical obstruction, microbial proliferation, and immune-mediated amplification in driving the severity of ascending cholangitis.

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 , fever with chills, and , which is observed in approximately 15-40% of cases according to recent studies, lower than earlier estimates of 50-70%. The abdominal pain is often colicky and may radiate to the back or , while the fever can be high-grade and accompanied by rigors. results from biliary obstruction leading to elevation, manifesting as yellowing of the skin and . Patients may also experience additional symptoms such as , , , and, in severe cases, altered mental status due to systemic effects of . In severe cases, the addition of and altered mental status to Charcot's triad forms , observed in 10-20% of patients and indicating . These features can vary in intensity but commonly contribute to overall and discomfort. On physical examination, right upper quadrant abdominal tenderness is a prominent finding. Signs of , such as dry mucous membranes, or shock, including and , may be evident in more advanced presentations. 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.

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. Grade I (mild) is defined as acute cholangitis with but without or the need for urgent biliary drainage, typically managed with antibiotics and supportive care alone. Grade II (moderate) involves the presence of at least two clinical predictors of severity, including (>12,000/μL) or (<4,000/μL), high fever (≥39°C), age ≥75 years, hyperbilirubinemia (>5 mg/dL), or (<25 g/L or <0.7 times the lower limit of normal). These predictors indicate a higher risk of complications, necessitating early biliary decompression in addition to medical therapy. 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). This grade demands intensive care, including hemodynamic stabilization and emergent biliary drainage once the patient is stable. Key clinical predictors like advanced age (>75 years), hyperbilirubinemia (>5 mg/dL), and further stratify risk within these grades, with older patients showing heightened vulnerability to progression. The TG18 severity grading also serves as a prognostic tool, incorporating components of (e.g., fever and ), cholestasis (e.g., levels), and to enable risk stratification and timely intervention. 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.

Diagnosis

Laboratory tests

Laboratory investigations play a crucial role in supporting the of by demonstrating evidence of , , and potential . Initial tests typically include a , , inflammatory markers, cultures, studies, and renal function assessment. Inflammatory markers often reveal , with counts exceeding 10,000/μL in most cases, reflecting the systemic inflammatory response to biliary . C- levels are commonly elevated above 1 mg/dL, serving as a sensitive indicator of inflammation. levels may be measured to help assess severity, as elevated concentrations are associated with severe bacterial infections in the biliary tree. Liver function tests characteristically show a cholestatic pattern, with total levels ≥2 mg/dL indicating obstructive . is markedly elevated, often more than twice the upper limit of normal, due to biliary obstruction. Transaminases, such as and aspartate aminotransferases, exhibit only mild elevations, distinguishing cholangitis from hepatocellular . Blood cultures are positive in 20-70% of cases, identifying common pathogens like and 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 or international normalized ratio (PT/INR >1.5) in severe cases, reflecting hepatic dysfunction or . Renal function tests can demonstrate elevated serum creatinine levels (>2 mg/dL) in patients with associated , indicating .

Imaging studies

serves as the initial modality of choice for suspected ascending cholangitis due to its non-invasive nature, wide availability, lack of , and ability to rapidly assess for biliary obstruction. It effectively detects (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, 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 walls, a hallmark finding in the appropriate clinical context, further supports the . In more complex cases or when is inconclusive, computed tomography (CT) or is employed to delineate the and extent of biliary . CT excels in identifying complications such as periductal inflammation, abscesses, strictures, or underlying malignancies, providing comprehensive evaluation of the and staging potential tumors, though it has lower sensitivity for choledocholithiasis compared to other modalities. , 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 and high diagnostic accuracy without the need for contrast agents in stable patients. Endoscopic retrograde cholangiopancreatography (ERCP) and (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 , offering direct duct opacification to identify obstructive lesions. Both modalities enable assessment of infection-related changes like or debris within the ducts. Recent advancements as of 2025 highlight the expanding role of (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.

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 . These criteria, current as of 2025, are divided into three parts: Part A assesses , Part B evaluates , and Part C confirms the biliary through imaging. Part A requires of , including fever and/or shaking chills, or laboratory indicators such as count >10,000/mm³ or <4,000/mm³, or level of at least 1 mg/dL. Part B involves signs of , such as with total ≥2 mg/dL (≥34.2 μmol/L) or abnormal including , gamma-glutamyl transferase, aspartate aminotransferase, or elevated to at least 1.5 times the upper limit of normal. Part C mandates imaging findings like biliary dilatation or direct of the underlying cause, such as a stone, stricture, or in the . A suspected diagnosis is made when one item from Part A and one from Part B are present, prompting urgent evaluation. A definite requires fulfillment of one item from each part (A + B + C), providing high diagnostic accuracy. Validation studies report varying , such as 86% sensitivity and 63% specificity in one post-ERCP cohort. Differential diagnosis considerations include , which typically presents with right upper quadrant pain and fever but lacks prominent and biliary dilatation on , and , characterized by epigastric pain radiating to the back with elevated / but without cholestatic liver enzyme patterns. 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.

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 and infection, particularly in those with hemodynamic instability or . This approach is guided by severity assessment, with more aggressive interventions for severe cases involving . 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. 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. Empiric broad-spectrum intravenous antibiotics are initiated immediately upon suspicion of ascending cholangitis to cover common enteric pathogens, including gram-negative bacilli like and species, as well as enterococci and anaerobes. Preferred regimens include piperacillin-tazobactam (4.5 g every 6 hours) as first-line therapy, or alternatives such as a (e.g., ) in regions with high extended-spectrum prevalence, or plus for penicillin-allergic patients. Therapy should be de-escalated based on blood and biliary culture results, typically within 48-72 hours, to narrow coverage and minimize resistance. 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. Supportive care includes analgesia with opioids for , antiemetics such as for , and close monitoring of and organ function. Patients with severe , characterized by altered mental status or shock, require admission for advanced hemodynamic support, including vasopressors if fluid resuscitation alone is insufficient.

Biliary decompression

Biliary decompression is essential for resolving the obstruction that perpetuates in ascending cholangitis, with (ERCP) serving as the preferred initial method due to its efficacy in achieving drainage and addressing the underlying cause. During ERCP, endoscopic sphincterotomy is typically performed to facilitate access, followed by stone extraction if choledocholithiasis is present or placement of a biliary to restore flow. This approach yields technical success rates exceeding 90% in most cases, particularly when performed by experienced endoscopists. According to the Tokyo Guidelines 2018 (TG18), timing of decompression is guided by 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. Delaying beyond this window in moderate or severe cholangitis increases risks of complications and mortality. When ERCP is unsuccessful or contraindicated, such as in patients with altered or hemodynamic instability, percutaneous transhepatic cholangiography (PTC) with biliary drainage is employed as an alternative to provide external or internal-external decompression. PTC involves - or fluoroscopy-guided needle access to the biliary tree for placement, offering reliable relief in up to 95% of suitable candidates and serving as a bridge to definitive . 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. These fully covered designs, often with anti-migration features, have improved clinical outcomes in inoperable cases by enhancing drainage durability and .

Surgical options

Surgical interventions for ascending cholangitis are typically reserved for definitive of underlying causes after initial biliary decompression, particularly in cases where endoscopic approaches fail or are not feasible. These procedures aim to address obstructions such as gallstones, strictures, or tumors, thereby preventing recurrence. 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. Laparoscopic is preferred due to its minimally invasive nature, lower complication rates, and shorter recovery time compared to open . Early or index admission , 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. For cases involving bile duct strictures, tumors, or failed endoscopic stone extraction, choledochotomy—surgical exploration and incision of the —or biliary reconstruction procedures such as Roux-en-Y hepaticojejunostomy are indicated. These interventions, often performed via open , 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 . However, emergency surgical decompression carries higher mortality rates (20-60%) and morbidity compared to endoscopic methods, underscoring its role as a salvage option. Indications for include persistent obstruction despite endoscopic or percutaneous drainage, multiple recurrent episodes, or underlying requiring resection. Biliary drainage serves as a bridge to these elective or urgent procedures in hemodynamically stable patients. As of 2025, robotic-assisted approaches, such as robotic exploration (RACBDE), are increasingly utilized for complex cases, including in elderly patients with choledocholithiasis contributing to cholangitis. These techniques offer enhanced precision, reduced conversion to open , and improved outcomes in minimally invasive stone clearance, though they remain more costly than standard .

Complications and prognosis

Acute complications

Ascending cholangitis, if untreated or inadequately managed, can rapidly progress to biliary , characterized by systemic dissemination of pathogens leading to bacteremia in 25-40% of cases. This bacteremia often escalates to , a life-threatening condition involving profound and tissue hypoperfusion, with mortality rates reaching 10-30% in instances of delayed biliary drainage. in this context stems from the overwhelming inflammatory response to ascending bacterial infection, primarily involving gram-negative organisms such as . 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. Multi-organ failure frequently complicates severe cases, manifesting as hepatic dysfunction, respiratory distress, and cardiovascular collapse due to the cascading effects of endotoxemia. 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. Key risk factors for these acute complications include delayed biliary decompression beyond 48 hours, which significantly heightens the likelihood of progression to and organ failure. Elderly patients face elevated risks due to diminished physiological reserve and higher prevalence of . Comorbidities such as , , or pre-existing renal disease further compound vulnerability by impairing and biliary clearance mechanisms. Prompt source control through biliary drainage remains essential to mitigate these complications, as it interrupts the infectious nidus and halts progression, reducing overall mortality to less than 10% with timely intervention.

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%. In severe untreated cases, however, mortality can escalate to up to 50%, primarily due to progression to and multiorgan failure. 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. 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. Long-term sequelae may include the development of chronic or recurrent pyogenic cholangitis, characterized by repeated infections and biliary obstruction. In patients with frequent recurrences, progressive hepatic parenchymal damage can lead to liver and . Additionally, post-endoscopic retrograde cholangiopancreatography (ERCP) , a potential complication of drainage procedures, occurs in about 5% of cases and may contribute to chronic pancreatic insufficiency in severe instances. 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.

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