What is cholangitis?

Cholangitis: Definition and Management

Cholangitis is an infectious disease characterized by acute inflammation and infection in the bile ducts resulting from a combination of biliary obstruction and bacterial growth in bile. 1

Definition and Pathophysiology

• Cholangitis occurs when there is biliary obstruction combined with bacterial colonization of the bile ducts, with bacteria reaching the biliary system either by ascending from the intestine or through the portal venous system 1
• The most common cause of cholangitis is choledocholithiasis (bile duct stones), which creates stasis and provides an environment for bacterial proliferation 1
• Increased biliary pressure leads to biliovenous reflux of bacteria and purulent bile into the circulation, causing systemic inflammation and sepsis with subsequent organ dysfunction 2

Clinical Presentation

• Classic presentation includes Charcot's triad (fever, jaundice, and abdominal pain), though many patients do not present with all three symptoms 3
• Symptoms can range from mild to severe with septic shock, and presentation may be atypical, particularly in patients with primary sclerosing cholangitis (PSC) 1
• In PSC patients, signs of bacterial cholangitis can be mild and nonspecific, and patients may present without significant changes in baseline liver biochemistry as infections can be limited to smaller segments of the liver 1

Diagnosis

• Diagnosis is based on clinical presentation, laboratory findings, and imaging studies 1
• According to recently proposed criteria for cholangitis in PSC patients, diagnosis requires either:
  • A single criterion (suppurative cholangitis on ERCP), or
  • At least 1 major criterion (body temperature >38°C, leukocyte count >12/nl, or C-reactive protein >75 mg/L), and
  • At least 2 minor criteria (positive bile culture, increase in ALP or total bilirubin above 2x ULN, no other focus of infection) 1
• Imaging studies such as ultrasound, CT scan, MRCP, or ERCP are essential to identify the underlying cause of obstruction 1

Microbiology

• Biliary infections are often polymicrobial 1
• The most common organisms isolated include Escherichia coli, Klebsiella, Enterococcus, Clostridium, Streptococcus, Pseudomonas, and Bacteroides species 1
• Blood and bile cultures should be obtained to guide antibiotic therapy, as there is a high rate of antibiotic resistance 4
• One study found that 72% of patients had positive blood cultures with at least one resistant organism present, and 36% had organisms resistant to multiple antibiotics 4

Management

Antibiotic Therapy

• Prompt initiation of antimicrobial therapy is crucial for improving survival 1
• For patients presenting with sepsis, appropriate antibiotics should be initiated within 1 hour of diagnosis; in less severe cases, within 6 hours 1
• Common first-line agents for mild episodes include fluoroquinolones such as ciprofloxacin 1
• More severe cases are usually treated with intravenous cephalosporins or extended spectrum penicillins with anaerobic coverage 1
• Antifungal therapy should be considered in those with cholangitis not responding to antibiotic therapy, as Candida species have been isolated from bile in some patients 1

Biliary Decompression

• Acute bacterial cholangitis should be treated with antibiotics and subsequent biliary decompression if an underlying relevant stricture is present 1
• The timing of biliary decompression is dictated by the severity of acute cholangitis:
  • Severe (grade 3) acute cholangitis requires urgent decompression
  • Moderate (grade 2) acute cholangitis requires early decompression
  • Mild (grade 1) acute cholangitis can be initially observed on medical treatment 1
• Early biliary drainage (within 24 hours after admission) has been associated with lower 30-day mortality in grade 2 acute cholangitis 1
• ERCP is the treatment of choice for biliary decompression in patients with moderate/severe acute cholangitis 1
• A randomized controlled trial demonstrated that endoscopic nasobiliary drainage + endoscopic sphincterotomy had significantly lower morbidity and mortality than T-tube drainage under laparotomy 1
• Endoscopic biliary decompression options include biliary stent or nasobiliary drain placement above the obstruction site ± sphincterotomy 1
• Percutaneous transhepatic biliary drainage (PTBD) should be reserved for patients in whom ERCP is unsuccessful or not feasible 2

Complications and Prognosis

• If left untreated, cholangitis can progress to septic shock, multiple organ dysfunction, and death 3
• Historically, mortality from cholangitis approached 100%, but with early recognition, antibiotics, resuscitation, and biliary decompression, outcomes have significantly improved 3
• Current mortality rates are still as high as 15% despite advances in antimicrobial therapy and improved access to emergency biliary tract decompression procedures 5
• Recurrent episodes of cholangitis may contribute to disease progression in patients with PSC 1

Special Considerations

• ERCP is a major risk factor for cholangitis in PSC patients, especially with stenting, and prophylactic antibiotics should be routinely used 1
• In patients with PSC, cholangitis was reported as the most common PSC-related clinical event, observed in 13% of patients over a median follow-up of 23 months 1
• High-grade strictures with stagnation of bile facilitate bacterial colonization, with bacterial infection of bile reported in 62% of PSC patients with high-grade strictures 1
• Portal bacteremia, reported in patients with active colitis, may be another important contributing factor to cholangitis 1