Do primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) increase the risk of ascending cholangitis?

PSC Significantly Increases Risk of Ascending Cholangitis; PBC Does Not

Primary sclerosing cholangitis (PSC) substantially increases the risk of ascending cholangitis, while primary biliary cholangitis (PBC) does not carry this same risk. The fundamental difference lies in the disease mechanisms: PSC creates biliary strictures and stagnation that facilitate bacterial colonization, whereas PBC primarily affects small intrahepatic bile ducts without creating the structural conditions that predispose to ascending infection.

PSC and Cholangitis Risk

Baseline Risk in PSC

• Cholangitis is the most common PSC-related clinical event, occurring in 13% of patients over a median follow-up of 23 months 1
• Bacterial cholangitis can be the initial presentation of PSC in approximately 6% of patients 1
• The annual risk of cholangitis in PSC patients is substantial and represents a major cause of morbidity 1

Mechanisms of Increased Risk

High-grade strictures are the primary driver of cholangitis risk in PSC. The pathophysiology involves:

• Bile stagnation behind strictures facilitates bacterial colonization - bacterial infection occurs in 62% of PSC patients with high-grade strictures versus only 31% without strictures 1
• Enteric bacteria are found in bile of 51% of patients with high-grade stenosis but never in absence of significant strictures 1
• Portal bacteremia from active colitis (common in PSC patients with IBD) provides another route for biliary infection 1

Procedural Risk Amplification

ERCP is a major risk factor for bacterial cholangitis in PSC and prophylactic antibiotics should be routinely administered 1, 2:

• Positive bile cultures increase from 25% in ERCP-naive PSC patients to 60% in those with previous ERCP 1
• Biliary stenting dramatically increases cholangitis risk - one randomized trial showed 12% cholangitis rate with short-term stents versus 3% with balloon dilatation alone 1
• Meta-analyses demonstrate prophylactic antibiotics prevent cholangitis (RR: 0.54), septicemia (RR: 0.35), and bacteremia (RR: 0.50) 1, 2

Clinical Management Implications

For PSC patients with recurrent cholangitis:

• High-grade strictures require urgent biliary decompression as mortality is high without treatment 1
• Antibiotic therapy alone is insufficient without endoscopic drainage of obstructions 1
• Some patients with severe recurrent cholangitis may require permanent rotating antibiotics until liver transplantation 1
• Duct-to-duct biliary anastomosis at transplant is associated with lower cholangitis risk compared to choledochojejunostomy 1

PBC and Cholangitis Risk

PBC does not inherently increase the risk of ascending cholangitis. The key distinctions are:

• PBC affects small intrahepatic bile ducts (interlobular and septal ducts) without creating the large duct strictures that predispose to bacterial cholangitis 1
• There is no mention of cholangitis as a complication of PBC in major guidelines covering PBC management 1
• The disease mechanism involves immune-mediated destruction of small bile ducts rather than stricturing disease 3

Important Caveat

If a patient has overlap syndrome (features of both PSC and PBC), the cholangitis risk would be determined by the presence and severity of PSC-type stricturing disease 4. However, this represents a distinct clinical entity rather than PBC alone.

Practical Clinical Algorithm

When evaluating cholangitis risk:

1. PSC patients: Assume elevated baseline risk, intensify with high-grade strictures or prior ERCP
2. PBC patients: No increased baseline risk unless overlap features present
3. Before any ERCP in PSC: Mandatory prophylactic antibiotics 1, 2
4. PSC with recurrent cholangitis: Evaluate for dominant strictures requiring intervention 1

The mortality and morbidity implications are substantial - untreated severe cholangitis with high-grade strictures in PSC carries high mortality, making recognition and aggressive management essential 1.