Acute Cholangitis

Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. The diagnosis is confirmed with ultrasound showing dilation of the common bile duct (CBD) or gallstones, elevated liver function tests, and leukocytosis. Treatment includes hemodynamic stabilization, broad-spectrum antibiotics, urgent biliary drainage, and cholecystectomy to prevent recurrence.

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Overview

Epidemiology

  • Relatively uncommon
  • Men and women are equally affected.
  • More common in adults
  • Peak incidence is in the 6th and 7th decades of life.
  • Increased incidence in Northern Europeans, Hispanics, and Native Americans

Etiology

  • Obstruction of the biliary system:
    • Choledocholithiasis (responsible for 60% of cases)
    • Biliary strictures
    • Malignancy
    • Extrinsic compression (pancreatic pseudocyst or acute pancreatitis)
    • Parasites (Ascaris lumbicoides
  • Iatrogenic manipulation of the bile tract:
    • ERCP (endoscopic retrograde cholangiopancreatography) 
    • Sphincterotomy
    • Stent placement
  • Causative organisms:
    • Gram-negative bacteria (most common)
      • Escherichia coli
      • Klebsiella 
      • Pseudomonas
      • Serratia
      • Proteus
      • Bacteroides
    • Gram-positive bacteria
      • Enterococcus
      • Streptococcus
      • Clostridia

Mnemonic: Bacteria responsible for cholangitis—KEEPS:

  • K: Klebsiella
  • E: Enterococcus
  • E: E. coli
  • P: Proteus
  • S: Serratia

Pathophysiology

  • Obstruction of the common bile duct (CBD) → biliary stasis → bacteria ascend from the duodenum → bacterial overgrowth and suppuration → biliary sepsis 
  • Disruption of the sphincter of Oddi can result in a loss of the mechanical barrier to duodenal reflux → ascension of bacteria and subsequent infection

Clinical Presentation

  • Charcot’s triad (50%–75% of patients will have all 3 features): 
    1. Right upper quadrant (RUQ) abdominal pain 
    2. Fever 
    3. Jaundice
  • Reynold’s pentad (signals severe disease): 
    1. RUQ abdominal pain 
    2. Fever 
    3. Jaundice 
    4. Hypotension 
    5. Altered mental status
  • Other signs or symptoms:
    • Nausea and vomiting
    • Abdominal distention
    • Acholic (without bile) stools
    • Dark urine
    • Pruritus
    • Tachycardia

Diagnosis

Laboratory tests

  • ↑ WBC count
  • Hepatic function test
    • ↑ alkaline phosphatase (ALP), bilirubin, and gamma-glutamyl transpeptidase (GGT) → cholestasis
    • Mild ↑ AST (aspartate aminotransferase) and ALT (alanine aminotransferase)
  • Lipase → rule out concurrent pancreatitis
  • Blood cultures → potentially isolate the causative organism

Imaging

Note: If the patient is hemodynamically unstable and has clinical evidence of acute cholangitis, this imaging workup will be skipped. The patient should proceed directly to biliary decompression.

  • Abdominal ultrasound (US) 
    • Possible findings: 
      • Biliary duct dilation (most common finding) 
      • Gallstones
    • A normal US does not rule out acute cholangitis.
  • Computed tomography (CT)
    • Can be used if ultrasound is unremarkable
    • Possible findings: 
      • Dilated intrahepatic and extrahepatic ducts 
      • Inflammation of the biliary tree 
      • Malignancy
      • Abscesses 
    • Gallstones are poorly visualized.
  • Magnetic resonance cholangiopancreatography (MRCP)
    • Used if US or CT is not diagnostic
    • Possible findings: 
      • Choledocholithiasis
      • Biliary strictures
      • Ductal dilation
      • Malignancy
  • Biliary scintigraphy (hepatobiliary iminodiacetic acid (HIDA))
    • Detects biliary obstruction
    • Takes time, therefore not recommended for critical or unstable patients
  • Endoscopic retrograde cholangiopancreatography (ERCP)
    • Diagnostic and therapeutic
    • May skip the above imaging and proceed directly to ERCP in patients with Charcot’s triad and elevated liver tests
Gallbladder wall thickening acute cholangitis

Acute cholangitis: Abdominal ultrasound showing gallbladder wall thickening, pericholecystic fluid and cholelithiasis (a). The common bile duct is dilated (b).

Image: “Abdominal ultrasound” by Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Avenida Professor Egas Moniz, Lisboa, 1649-035, Portugal. License: CC BY 4.0

Management

  • Assess the patient’s vital signs to determine whether emergent biliary drainage is required (see algorithm below).
  • Supportive therapy:
    • Intravenous fluid resuscitation
    • Electrolyte correction
    • Close vital sign monitoring
    • Vasopressors for septic shock
    • Intensive care unit admission for critical patients
  • Antibiotic coverage for gram negatives and anaerobes:
    • Ciprofloxacin or levofloxacin plus metronidazole
    • 3rd- or 4th-generation cephalosporins plus metronidazole
    • Piperacillin-tazobactam
    • Ertapenem
  • Biliary decompression:
    • ERCP 
      • With sphincterotomy and stone extraction
      • Usually the treatment of choice
    • Percutaneous transhepatic cholangiogram (PTC) with catheter drainage 
      • Requires a dilated biliary system
      • Involves transhepatic insertion of a needle into the bile duct, allowing drainage and stone extraction
      • Performed if ERCP is not available or unsuccessful
    • Surgery
      • Reserved for patients who fail the above interventions
      • Cholecystectomy can usually be performed at the same time.
  • All patients with gallstones should also be evaluated for cholecystectomy to prevent recurrence.
Acute cholangitis options

A simplified management algorithm for acute cholangitis based on the hemodynamic stability of the patient: Definitive treatment requires source control with biliary drainage. Therefore, this treatment is performed emergently in patients who are hemodynamically unstable.

Image by Lecturio.

Complications and Prognosis

Complications

  • Septic shock
  • Liver abscess or microabscesses
  • Acute renal failure
  • Liver failure
  • Procedure complications
    • Bleeding
    • Fistula formation
    • Bile leak

Prognosis

  • May be life-threatening, especially in the elderly or immunocompromised
  • Mortality rate
    • Approximately 11% overall
    • 20%–30% in severe disease
  • Depends on:
    • Early recognition and diagnosis
    • Response to treatment
    • Patient comorbidities
  • Higher morbidity and mortality seen with:
    • Women
    • Age > 50 years
    • Cirrhosis
    • Failure to respond to antibiotics
    • Liver abscess
    • Acute renal failure

Differential Diagnosis

The following table outlines common biliary diagnoses and how they may be differentiated from acute cholangitis:

ConditionPathologyClinical presentationDiagnosisManagement
CholelithiasisPresence of gallstones in the gallbladderAsymptomatic or biliary colic (constant, dull RUQ pain lasting < 6 hours)
  • US
  • Normal blood tests
  • None, if asymptomatic
  • Cholecystectomy if symptomatic
CholecystitisCystic duct obstruction with inflammation of the gallbladderConstant RUQ pain (> 6 hours), fever, nausea and vomiting, Murphy’s sign
  • US
  • HIDA (if US is equivocal)
  • Blood tests: ↑ WBC
  • Liver tests may be normal or mild ↑
  • Urgent cholecystectomy
  • Antibiotics
CholedocholithiasisCBD obstruction due to a stonePostprandial colicky RUQ pain > 6 h, jaundice
  • US
  • MRCP (if US is equivocal)
  • Blood tests: ↑ ALT, ↑ AST, ↑ ALP, ↑ bilirubin
ERCP and cholecystectomy
Acute cholangitisBile duct infectionRUQ pain, fever, jaundice, hypotension, tachycardia
  • US
  • ERCP
  • Blood tests: ↑ ALT, ↑ AST, ↑ bilirubin, ↑ WBC
  • ERCP and cholecystectomy
  • Antibiotics
  • Sepsis management

Other potential diagnoses to consider:

  • Acute appendicitis: an infection of the appendix. Patients present with right lower quadrant or periumbilical pain, fever, guarding, and tenderness at Mcburney’s point. Diagnosis is based on history and exam, and is supplemented by imaging showing appendiceal thickening and fat stranding. The location of pain and imaging differentiate this condition from acute cholangitis. Treatment involves antibiotics and surgical removal of the appendix. 
  • Acute pancreatitis: inflammation of the pancreas. Patients present with a sudden onset of severe epigastric pain that is typically sharp and radiates to the back. Acute pancreatitis is associated with alcohol abuse and gallstones. Characteristic abdominal pain, lipase elevation, or imaging revealing pancreatic edema will give the diagnosis and differentiate the condition from acute cholangitis. Treatment includes bowel rest, pain control, and intravenous fluid hydration.
  • Nephrolithiasis: also known as kidney stones, which can irritate or obstruct the ureters. Patients present with sudden onset of severe, colicky flank pain; nausea; vomiting; and hematuria. Imaging will show stones in the kidney, ureter, or bladder. The history, exam, and imaging will differentiate this condition from acute cholangitis. Nephrolithiasis can be treated with supportive care, pain control, ureteral stents, lithotripsy, or surgery. 
  • Liver abscess: an abscess located in the liver, usually due to a bacterial infection. Patients will present with fever, RUQ abdominal pain, nausea, vomiting, and jaundice. Abdominal exam may reveal guarding and rebound tenderness. Laboratory tests will show leukocytosis and increased liver enzymes. Ultrasound or CT will reveal the diagnosis and differentiate this condition from acute cholangitis. Antibiotics are given, and the abscess needs to be drained with CT guidance, ERCP, or surgery.

References

  1. Zakko, S. (2019). Acute cholangitis: Clinical manifestations, diagnosis, and management. In Chopra, S and Grover, S (Eds.), UpToDate. Retrieved November 5, 2020, from https://www.uptodate.com/contents/acute-cholangitis-clinical-manifestations-diagnosis-and-management
  2. Scott, T.M., Rosh, A.J. (2017). Acute cholangitis. In Brenner, B.E. (Ed.), Medscape. Retrieved November 10, 2020, from https://emedicine.medscape.com/article/774245-overview
  3. Lindenmeyer, C.C. (2020). Choledocholithiasis and cholangitis.[online]. MSD Manual Professional Edition. Retrieved November 10, 2020, from https://www.msdmanuals.com/professional/hepatic-and-biliary-disorders/gallbladder-and-bile-duct-disorders/choledocholithiasis-and-cholangitis

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