67. Cholangitis

1. Definition

• Acute (ascending) cholangitis → bacterial infection of the bile ducts caused by biliary obstruction and stasis
• Needs two things → obstruction plus infected bile
• Recurrent pyogenic cholangitis (oriental cholangiohepatitis) → repeated infection with intrahepatic brown pigment stones and strictures
• Primary sclerosing cholangitis (PSC) → chronic autoimmune fibrosing disease of the ducts (not infective; see differential)

2. Epidemiology

• Acute cholangitis → complicates about 6–9% of admissions with gallstones
• Median age 50–60; equal sex
• Mortality → over 50% before modern drainage; now about 2–10% (higher in severe cholangitis)
• Recurrent pyogenic cholangitis → East Asia (parasites, malnutrition)
• Iatrogenic → after ERCP or with blocked stents; after biliary-enteric anastomosis

3. Aetiology and risk factors

Causes of obstruction

• CBD stones (choledocholithiasis) → most common (about 30–70%)
• Malignant stricture → pancreatic head cancer, cholangiocarcinoma, ampullary cancer, gallbladder cancer, nodes at the porta (infection rarer than with stones, more after instrumentation)
• Benign stricture → after cholecystectomy (bile duct injury), chronic pancreatitis, PSC, anastomotic stricture
• Blocked biliary stent, after ERCP or PTC
• Parasites → Ascaris lumbricoides, Clonorchis sinensis, Opisthorchis, Fasciola
• Choledochal cyst, Mirizzi syndrome, periampullary diverticulum
• Sump syndrome (after side-to-side choledochoduodenostomy)
• Hydatid cyst rupture into the ducts

Organisms

• Usually ascend from the duodenum (and portal blood)
• Gram-negative → E. coli (most), Klebsiella, Enterobacter, Pseudomonas (after instrumentation)
• Enterococcus
• Anaerobes → Bacteroides, Clostridium (elderly, biliary-enteric anastomosis)
• Often polymicrobial

4. Pathogenesis

1. Bile duct blocked → bile stasis
2. Bacteria multiply in stagnant bile (normal bile is sterile; sphincter of Oddi and bile flow protect)
3. Pressure in the ducts rises (over 20–25 cm H₂O)
4. Cholangiovenous and cholangiolymphatic reflux → bacteria and endotoxin pass into the blood
5. Bacteraemia, septic shock, multiorgan failure
6. Untreated → liver abscesses, suppurative cholangitis (pus in the ducts)
7. Key point → antibiotics alone cannot clear an obstructed system; the duct must be drained

5. Classification

Tokyo Guidelines 2018 (TG18): diagnosis

• A Systemic inflammation → fever (over 38 °C) or rigors; raised white cell count or CRP
• B Cholestasis → jaundice (bilirubin ≥ 34 µmol/L); abnormal LFT
• C Imaging → biliary dilatation; cause seen (stone, stricture, stent)
• Suspected → A + B or C; definite → A + B + C

Tokyo Guidelines 2018: severity

• Grade I (mild) → responds to initial treatment
• Grade II (moderate) → any two of:
  • White cell count over 12 or under 4 × 10⁹/L
  • Fever ≥ 39 °C
  • Age ≥ 75
  • Bilirubin ≥ 85 µmol/L (5 mg/dL)
  • Albumin under 0.7 × lower limit
• Grade III (severe) → organ dysfunction (cardiovascular, neurological, respiratory, renal, hepatic, haematological)

Other

• Acute, recurrent, suppurative
• Recurrent pyogenic cholangitis
• Charcot's triad and Reynolds' pentad (clinical)

6. Clinical picture

Symptoms

• Charcot's triad (about 50–70%):
  1. Fever with rigors
  2. Jaundice
  3. RUQ pain
• Reynolds' pentad (severe, suppurative; about 5–7%) → Charcot's triad plus:
  1. Hypotension (shock)
  2. Confusion
• Dark urine, pale stools, itch
• Elderly → may present with confusion, falls or hypotension only
• History → gallstones, biliary surgery, stent, ERCP

Signs

• High swinging fever, rigors
• Jaundice
• RUQ tenderness; usually no peritonism
• Septic shock → tachycardia, hypotension, oliguria, altered mental state
• Liver may be tender and enlarged

7. Diagnosis

• Bloods:
  • FBC → leucocytosis (or low white count in severe sepsis)
  • CRP
  • LFT → raised bilirubin, ALP, GGT (cholestatic); transaminases may rise sharply early with a stone
  • U&E, creatinine, coagulation (INR), platelets, albumin
  • Blood cultures (positive in 20–70%), lactate, blood gas
  • Amylase or lipase (gallstone pancreatitis)
• Ultrasound → first test: dilated CBD (over 6–7 mm) and intrahepatic ducts, stones, liver abscess
• CT → cause (tumour, stricture, stent), abscess; dilated ducts
• MRCP → stones and strictures; plan therapy in stable patients
• EUS → small stones, ampullary tumours
• ERCP → diagnostic and therapeutic; bile culture
• Score sepsis → qSOFA, SOFA; Tokyo grade

8. Differential diagnosis

• Acute cholecystitis (no or mild jaundice, Murphy's sign)
• Gallstone pancreatitis (often together)
• Liver abscess
• Viral or alcoholic hepatitis
• Right lower lobe pneumonia, pyelonephritis (fever and pain)
• Primary sclerosing cholangitis (chronic, ulcerative colitis, beaded ducts)
• IgG4-related sclerosing cholangitis
• Sepsis from another source with cholestasis

9. Treatment

Conservative

• Sepsis Six within the first hour:
  1. Oxygen
  2. Blood cultures
  3. IV antibiotics → broad-spectrum, e.g. piperacillin-tazobactam; or ceftriaxone with metronidazole; meropenem for severe or resistant cases (local guidance)
  4. IV fluids (balanced crystalloid)
  5. Lactate
  6. Urine output (catheter)
• Correct coagulopathy (vitamin K, FFP or platelets before procedures)
• Critical care → vasopressors, organ support for grade III
• Antibiotics duration → 4–7 days after source control; 2 weeks if Enterococcus or streptococcal bacteraemia
• Analgesia

Surgical: biliary drainage

• Timing by Tokyo grade:
  • Grade I → antibiotics; drainage if no response in 24 hours; treat the cause (ERCP, cholecystectomy)
  • Grade II → early drainage within 24–48 hours
  • Grade III → urgent drainage as soon as organ support starts (within 12–24 hours)
• ERCP → first choice:
  • Endoscopic sphincterotomy with stone extraction, or
  • Plastic stent or nasobiliary drain alone in the very sick (quick decompression; stones cleared later)
  • Coagulopathy → stent without sphincterotomy
• Percutaneous transhepatic biliary drainage (PTBD) → ERCP failed or not possible (altered anatomy after gastric bypass or hepaticojejunostomy), hilar strictures
• EUS-guided biliary drainage (choledochoduodenostomy, hepaticogastrostomy) → failed ERCP in expert centres
• Open surgical drainage → rarely now; when endoscopic and percutaneous routes fail:
  • CBD exploration with T-tube drainage
  • Mortality much higher than endoscopic drainage in sick patients
• Definitive treatment of the cause once recovered:
  • Laparoscopic cholecystectomy after stone cholangitis (same admission or within weeks)
  • Cancer → staging and resection (Whipple, hepatectomy) or metal stent (palliation)
  • Benign strictures → endoscopic stents, Roux-en-Y hepaticojejunostomy
  • Recurrent pyogenic cholangitis → clear stones, hepatectomy of the affected segments, hepaticojejunostomy with access loop

10. Complications

• Septic shock, multiorgan failure, death
• Liver abscesses (multiple, pyogenic)
• Portal vein thrombosis (pylephlebitis)
• Acute kidney injury (sepsis, jaundice: hepatorenal)
• Recurrent cholangitis, secondary biliary cirrhosis (long-standing obstruction)
• ERCP complications → post-ERCP pancreatitis, bleeding after sphincterotomy, duodenal perforation, stent blockage or migration
• PTBD → bleeding (haemobilia), bile leak, catheter dislodgement

Prognosis

• Poor outcome → shock, confusion, renal failure, age over 75, malignant obstruction, delayed drainage
• Mortality → grade I under 2%; grade III about 5–10%