Last updated date: 26-Apr-2023

Originally Written in English




Acute cholangitis, also known as ascending cholangitis, is a potentially fatal infection of the biliary tree caused by an ascending bacterial infection. Choledocholithiasis is the most prevalent cause, with infection-causing stones in the common bile duct causing partial or full biliary system blockage. The clinical presentation, aberrant test values, and imaging investigations indicating infection and biliary blockage are used to make the diagnosis.

Early fluid resuscitation and antibiotic coverage are critical components of initial medical treatment. Septic shock might result from a delay in treatment. A biliary drainage operation may be accomplished with the use of endoscopic and surgical resources, depending on the course and severity of the condition.

When treated properly, acute cholangitis is a curable illness. However, if treatment is delayed for an extended period of time, mortality can be fairly high. Cholangitis may be classified into three types: primary biliary cholangitis, IgG4-related autoimmune cholangitis, and primary sclerosing cholangitis. 


Epidemiology of Cholangitis

Epidemiology of Cholangitis

Cholangitis is a rather rare condition. Annually, there are less than 200,000 instances of acute cholangitis in the United States. Individuals afflicted range in age from 50 to 60 years old. Males and females are equally affected. In the United States, 6–9% of hospitalized patients with gallstone disease are diagnosed with acute cholangitis.

The prevalence of cholelithiasis varies according to ethnicity. It is more common in Native Americans and Hispanics, less common in Whites, and much less common in Asians and African Americans. Furthermore, Asian populations and nations with intestinal parasites, as well as people with sickle cell disease, are at a higher risk. 


Pathophysiology of Cholangitis

Pathophysiology of Cholangitis

Bile is formed by the liver and serves to remove cholesterol and bilirubin from the body, as well as emulsify lipids to make them more water soluble and aid in digestion. Bile is produced by hepatocytes (liver cells) in the liver and expelled via the common hepatic duct. Because of back pressure (exerted by the sphincter of Oddi), some bile is held in the gall bladder and may be released during digestion.

In addition, the gallbladder concentrates bile by absorbing water and dissolved salts from it. The common bile duct and the ampulla of Vater transport all bile to the duodenum (initial section of the small intestine). The sphincter of Oddi is a circular muscle found at the intersection of the ampulla of Vater and the duodenum that regulates the flow of bile and pancreatic secretions into the digestive system.

Because of specific defensive processes, the biliary tree is typically bacteria-free. Oddi's sphincter serves as a mechanical barrier. The biliary system is generally under low pressure (8 to 12 cmH2O) and allows bile to flow freely. The continual forward flow of bile in the duct flushes bacteria, if present, into the duodenum and prevents infection from occurring. Bile salts and immunoglobulin, which are released by the bile duct epithelium, also have a protective effect.

Bacterial contamination alone does not generally cause cholangitis in the absence of blockage. However, increased pressure inside the biliary system (over 20 cmH2O) caused by bile duct blockage expands gaps between the cells lining the duct, allowing bacterially tainted bile to enter the blood stream. It also has a negative impact on the function of Kupffer cells, which are specialized macrophage cells that aid in the prevention of germs entering the biliary tract.

Finally, increasing biliary pressure reduces bile IgA immunoglobulin synthesis. This causes bacteremia (the presence of bacteria in the bloodstream) and the systemic inflammatory response syndrome (SIRS), which includes fever (often with rigors), tachycardia, increased respiratory rate, and an increase in white blood cell count; SIRS in the presence of a suspected or confirmed infection is known as sepsis.

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).

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. Other theories about the origin of the bacteria, such as through the portal vein or transmigration from the colon, are considered less likely. 


Microscopic features seen in Cholangitis

Cholangitis in Microscopic

Histological pictures of cholangitis show neutrophils inside the interlobular and infiltrating bile duct epithelial lumens. Furthermore, percutaneous liver biopsies frequently reveal cholestasis within the hepatic parenchyma as well as neutrophils in the bile duct lumen. 


What causes Cholangitis?

Cholangitis Causes

The most prevalent cause of acute cholangitis is a bacterial infection of the bile ducts. A biliary blockage is required for the development of acute cholangitis. Complete blockage can result in elevated biliary pressure, which commonly results in bacteremia.

The most common cause of biliary obstruction is caused by choledocholithiasis. Other causes include benign or malignant strictures of biliary ducts, pancreatic cancer, ampullary adenoma or cancer, porta hepatis tumor, parasites (Clonorchis sinensis, Fasciola hepatica), roundworm (Ascaris lumbricoides), tapeworm (Taenia saginata), biliary sludge deposits due to biliary stent obstruction, gallstone impaction in the neck of the gallbladder or the cystic duct leading to compression on common bile or common hepatic duct known as Mirizzi syndrome, peri-ampullary diverticulum of the duodenum leading to biliary obstruction known as Lemmel syndrome and acquired immunodeficiency syndrome (AIDS).

Pathogens that have been identified as the causal agents of acute ascending cholangitis include gram-negative and anaerobic organisms, with the most prevalent being E. coli, Klebsiella, Enterobacter, Pseudomonas, and Citrobacter.

In patients with biliary blockage, iatrogenic bacterial introduction is prevalent during endoscopic retrograde cholangiopancreatography (ERCP). Increased triglyceride consumption, sedentary lifestyle, BMI larger than 30, and fast weight loss are the most important risk factors for the development of acute cholangitis. 


Signs and symptoms of Cholangitis

Signs and symptoms of Cholangitis

Cholangitis has a wide range of clinical manifestations, ranging from mild to severe, including life-threatening fulminant sepsis. Fever, chills, malaise, rigors, widespread abdominal discomfort, jaundice, pruritus, and pale stools.

Medical history, including recent cholecystectomy, cholelithiasis, post-ERCP, previous history of cholangitis, and history of AIDS, may increase the risk of cholangitis. Individuals with cholangitis tend to appear quite ill and often present with severe sepsis or septic shock. 

On physical exam, they present with fever, right upper quadrant tenderness, jaundice, abdominal distension, altered mental status, or hemodynamic instability.

A conclusive diagnosis of acute cholangitis would involve systemic manifestations of infection as well as endoscopic, percutaneous, or surgical evidence of purulent bile. Although technically feasible, it is invasive and may not be the greatest use of resources. As a result, clinical techniques such as the Charcot triad and Tokoyo guidelines have been adopted in clinical practice.

The clinical manifestations of cholangitis are fever, right upper abdomen discomfort, and jaundice, according to the Charcot triad. The Reynolds pentad augments the triad with impaired mental state and sepsis. Many individuals with acute cholangitis may not exhibit traditional symptoms and signs. The Charcot triad has a high specificity (95.9%), but a low sensitivity (26.4 %). Approximately 90 % have a fever, and 60 to 70 % are jaundiced.

The Tokyo guidelines have a sensitivity of 100% and a specificity of 87.4%, both of which are much higher than the Charcot triad. Tokoyo guidelines contain two of the three Charcot criteria, as well as systemic inflammation (raised white blood cell count and C-reactive protein rise), abnormal liver tests, imaging showing biliary dilatation, and evidence of etiology (e.g., biliary stones, strictures, and stents). 


How is Cholangitis evaluated?

Cholangitis Evaluation

Blood tests:

Routine blood tests reveal signs of acute inflammation (increased white blood cell count and C-reactive protein level) as well as abnormal liver function tests (LFTs). In most cases, elevated bilirubin, alkaline phosphatase, and -glutamyl transpeptidase levels will be consistent with blockage. However, in the early stages, pressure on the liver cells may be the most prominent sign, and the tests may be similar to those seen in hepatitis, with increases in alanine transaminase and aspartate transaminase.

Blood cultures are frequently conducted on patients who have a fever and signs of an acute infection. In 36% of cases, they give the bacteria causing the illness after 24–48 hours of incubation. During an ERCP, bile may also be submitted for culture. Gram-negative bacilli are the most commonly associated with ascending cholangitis: Escherichia coli (25–50%), Klebsiella (15–20%), and Enterobacter (5–10%). Enterococcus is responsible for 10–20% of gram-positive cocci.


Imaging modalities:

Given that ascending cholangitis is frequently associated with bile duct blockage, several techniques of medical imaging may be used to determine the location and nature of the obstruction. Because ultrasonography is the most readily available, it is frequently the initial investigation. Ultrasound can detect bile duct dilatation and identify 38% of bile duct stones; however, it is less effective in detecting stones farther down the bile duct.

Ultrasound can assist identify cholangitis from cholecystitis (gallbladder inflammation), which has similar symptoms to cholangitis but shows differently on ultrasound. Magnetic resonance cholangiopancreatography (MRCP), which employs magnetic resonance imaging (MRI), is a superior test with equivalent sensitivity to ERCP. Smaller stones, on the other hand, may be overlooked on MRCP depending on the hospital's capability.

Endoscopic retrograde cholangiopancreatography is still the gold standard test for biliary blockage (ERCP).  At that moment, radiocontrast is injected into the duct to obstruct it, and X-rays are taken to gain a visual of the biliary system. On an endoscopic view of the ampulla, a protuberant ampulla from an impacted gallstone in the common bile duct or a frank ejection of pus from the common bile duct orifice can be seen.

Gallstones are apparent as non-opacified spots in the contour of the duct on X-ray imaging (called cholangiograms). ERCP has mostly been supplanted with MRCP for diagnostic reasons. ERCP is only used first-line in severely sick patients who cannot wait for definitive testing; however, if the index of suspicion for cholangitis is high, an ERCP is usually performed to empty the clogged common bile duct.

If a tumor or other cause other than gallstones is suspected, computed tomography (CT) and endoscopic ultrasonography (EUS) may be used to determine the etiology of the blockage. EUS can be used to take a biopsy (tissue sample) of a suspected mass. EUS may also be used to diagnose stone disease instead of ERCP, albeit this is dependent on local availability. 


Treatment of Cholangitis 

Treatment of Cholangitis 

Fluids and antibiotics:

Cholangitis necessitates hospitalization. Intravenous fluids are given, particularly if the blood pressure is low, and antibiotics are started. Treatment with broad-spectrum antibiotics is typically required until it is determined which bacterium is causing the infection and which drugs it is susceptible to.

Combinations of penicillins and aminoglycosides are commonly utilized, however ciprofloxacin has been proven to be successful in the majority of instances and may be chosen over aminoglycosides due to less adverse effects. Metronidazole is frequently used to specifically treat anaerobic pathogens, particularly in people who are critically unwell or at risk of anaerobic infections. Antibiotics are used for 7–10 days. To counteract the low blood pressure, drugs that raise blood pressure (vasopressors) may be necessary.



The only way to cure cholangitis is to treat the underlying biliary blockage. This is normally postponed until 24–48 hours after admission, when the patient is stable and has improved with antibiotics, but it may be necessary as an emergency if the patient continues to deteriorate despite proper therapy, or if antibiotics are ineffective in lowering the symptoms of infection (which happens in 15 % of cases).

The most frequent method for unblocking the bile duct is endoscopic retrograde cholangiopancreatography (ERCP). Endoscopy (passing a fiberoptic tube through the stomach into the duodenum), identification of the ampulla of Vater, and insertion of a tiny tube into the bile duct are all part of the procedure. A sphincterotomy (cutting the sphincter of Oddi) is often performed to allow devices to be inserted to retrieve gallstones that are clogging the common bile duct; alternatively, or additionally, the common bile duct aperture can be expanded with a balloon.

Stones can be removed by direct suction or by trawling the bile duct with different tools such as balloons and baskets to pull stones into the duodenum. Obstructions produced by bigger stones may necessitate the use of a mechanical lithotriptor to smash the stone prior to removal. Extracorporeal shock wave lithotripsy may be used to treat obstructing stones that are too big to be removed or shattered mechanically by ERCP.

To break down the stones, acoustic shock waves are supplied outside the body. Electrohydraulic lithotripsy is an alternate approach for removing very big blocking stones, in which a tiny endoscope known as a cholangioscope is implanted via ERCP to directly see the stone. A probe generates shock waves that break down the blocking stone using electricity. To remove the stone, surgical exploration of the common bile duct (called choledochotomy) is sometimes necessary, which can be done by laparoscopy.

A stent, a hollow tube that maintains the duct open, can be used to cross narrow sections. In uncomplicated gallstone disease, removable plastic stents are utilized, however permanent self-expanding metal stents with a longer lifespan are employed if the blockage is caused by tumor pressure, such as pancreatic cancer. A nasobiliary drain, which is a plastic tube that travels from the bile duct via the stomach and nose and provides continuous bile drainage into a receptible, may be left behind.


Percutaneous biliary drainage:

When a patient is too unwell to endure endoscopy or when a retrograde endoscopic approach fails to reach the obstruction, a percutaneous transhepatic cholangiogram (PTC) may be performed to evaluate the biliary system in preparation for the installation of a percutaneous biliary drain (PBD). 

In the case of a proximal stricture or bilioenteric anastomosis, this is frequently required (a surgical connection between the bile duct and small bowel, such as the duodenum or jejunum). Once access is gained across the stricture, balloon dilation can be done and stones swept forward into the duodenum. Because of the possible hazards of percutaneous biliary drain placement and the need for frequent drain care, ERCP remains first-line treatment.



Although not all gallstones associated with ascending cholangitis originate in the gallbladder, cholecystectomy (surgical removal of the gallbladder) is often indicated in persons who have been treated for cholangitis caused by gallstone disease. 

This is usually postponed until all symptoms have subsided and an ERCP or MRCP has established that the bile duct is free of gallstones. Those who do not have a cholecystectomy have a higher chance of recurring biliary discomfort, jaundice, recurrent cholangitis, and the need for another ERCP or cholecystostomy; the risk of mortality is also greatly raised.


Complications of Cholangitis

Complications of Cholangitis

Acute cholangitis can range in severity from mild disease to liver or multiorgan failure. Following complications are associated with cholangitis:

  • Hepatic abscess
  • Acute cholecystitis.
  • Portal vein thrombosis.
  • Acute biliary pancreatitis.
  • Liver failure.
  • Acute renal failure.
  • Bacteremia/septicaemia.
  • Multiple organ failure.


Prognosis of Cholangitis

Prognosis of Cholangitis

Acute cholangitis is associated with a high risk of mortality, with irreversible shock and multiple organ failure being the most common cause. 

Improvements in diagnosis and treatment have resulted in a decrease in mortality: prior to 1980, the death rate was higher than 50%, while after 1980, it was 10–30%. Patients who show symptoms of multiple organ failure are likely to die unless they get early biliary drainage and systemic antibiotic therapy. Heart failure and pneumonia are two further reasons of mortality after severe cholangitis.

Older age, female gender, a history of liver cirrhosis, biliary narrowing due to cancer, acute kidney injury, and the presence of liver abscesses are risk factors for death. Complications from 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 infarction (lack of blood flow to the heart, leading to heart attacks).




Acute cholangitis (ascending cholangitis) is a bacterial infection of the biliary system that usually occurs as a result of biliary blockage and stasis (e.g., due to choledocholithiasis, biliary stricture).

The Charcot triad, which consists of RUQ pain, fever, and jaundice, is the hallmark clinical presentation of acute cholangitis, though it does not appear in all individuals.

Acute cholangitis is diagnosed based on a combination of clinical characteristics, evidence of systemic inflammation (i.e., leukocytosis, CRP), and evidence of cholestasis (e.g., elevated direct bilirubin, GGT, and ALP). The primary purpose of imaging is to determine the underlying etiology of biliary blockage.

The cornerstones of treatment are empiric antibiotic medication and prompt biliary drainage (e.g., ERCP + papillotomy, EUS-guided biliary drainage) within 48 hours of presentation. In stable patients with moderate cholangitis, treatment of the underlying cause (e.g., ERCP-guided stone extraction or CBD stenting) may be undertaken concurrently with urgent biliary draining, or postponed until clinical improvement in patients with severe cholangitis.