What are the most common causes of cholangitis?

Most Common Causes of Cholangitis

The most common cause of acute cholangitis is choledocholithiasis (common bile duct stones), which accounts for the majority of cases in clinical practice, followed by benign and malignant biliary strictures. 1, 2, 3, 4

Primary Obstructive Causes

The pathogenesis of cholangitis requires two essential components: bacterial colonization of bile and increased biliary pressure from obstruction. 2, 3 The most frequent obstructive causes include:

Choledocholithiasis (Most Common)

• Common bile duct stones are found in 7-20% of patients undergoing cholecystectomy and represent the leading cause of acute cholangitis. 4
• Stones create biliary stasis that allows bacterial multiplication, and increased biliary pressures enable bacteria to penetrate cellular barriers and enter the bloodstream. 3

Malignant Strictures

• Cholangiocarcinoma and other benign/malignant neoplasms are major causes of secondary sclerosing cholangitis leading to cholangitis. 1
• Perihilar cholangiocarcinoma is the leading cause of perihilar biliary strictures resulting in cholestatic jaundice. 1

Benign Strictures

• Post-surgical strictures (following cholecystectomy, liver transplantation, hepaticojejunostomy) are common causes. 1, 5
• Anastomotic strictures after liver transplantation frequently lead to cholangitis. 1

Primary Sclerosing Cholangitis (PSC)

In patients with PSC, cholangitis is the most common clinical event, occurring in 13% of patients over 23 months of follow-up. 6

• Bacterial cholangitis can be the initial presentation in approximately 6% of PSC patients. 6
• High-grade strictures are the primary driver of cholangitis risk, with enteric bacteria found in bile of 51% of patients with high-grade stenosis but never in absence of significant strictures. 1, 6
• Portal bacteremia from active inflammatory bowel disease provides another route for biliary infection in PSC patients. 1, 6

Infectious and Parasitic Causes

Bacterial Pathogens

The most common organisms causing cholangitis are: 1, 2

• Escherichia coli (most frequent)
• Klebsiella species
• Enterococcus species
• Enterobacter species
• Pseudomonas species
• Anaerobes (Bacteroides, Clostridium)

Most infections are polymicrobial. 2, 3

Parasitic Causes (Geographic Variation)

In endemic regions, biliary parasites are important causes: 2

• Ascaris lumbricoides (nematode)
• Clonorchis sinensis and Opisthorchis species (liver flukes)
• Fasciola hepatica
• Echinococcus species

These parasites cause cholangitis through direct irritation, physical obstruction, stone formation, and bacterial introduction during migration from the duodenum. 2

Iatrogenic and Procedural Causes

ERCP is a major risk factor for bacterial cholangitis, with positive bile cultures increasing from 25% in ERCP-naive patients to 60% in those with previous ERCP. 1, 6

• Biliary stenting dramatically increases risk: 12% cholangitis rate with short-term stents versus 3% with balloon dilatation alone. 1, 6
• Bacterobilia is reported in 55% of PSC patients at liver transplantation, increasing to 77% in those with previous biliary instrumentation. 1

Other Secondary Causes

Additional causes of secondary sclerosing cholangitis that predispose to cholangitis include: 1

• Immune-mediated: IgG4-related cholangitis, eosinophilic cholangitis, hepatic allograft rejection
• Ischemic: Hepatic artery thrombosis (especially post-transplant), sclerosing cholangitis of critically ill patients (including COVID-19-related)
• Toxic: Transarterial chemotherapy/embolization, ketamine
• Infectious: AIDS-related cholangiopathy (cryptosporidiosis, CMV), recurrent pyogenic cholangitis
• Other: Chronic pancreatitis, portal hypertensive biliopathy, Mirizzi syndrome

Critical Clinical Pitfall

A common pitfall is failing to recognize that antibiotic therapy alone is insufficient without biliary decompression in patients with high-grade strictures. 1, 6 Short-course antibiotics cannot eradicate bacteria from obstructed bile ducts, and patients with severe acute cholangitis and high-grade strictures require urgent biliary decompression as mortality is high without treatment. 1, 6