Cholangitis

Overview

Cholangitis, also called acute cholangitis or ascending cholangitis, occurs when obstructed biliary flow leads to cholestasis and infection of the biliary tree. Cholangitis is commonly caused by choledocholithiasis and a variety of pathologies that obstruct the biliary tree. The severity of cholangitis ranges from mild to life-threatening, with mortality rates approaching 10% for the most severe cases. Prompt diagnosis followed by fluid resuscitation, administration of antibiotics, and biliary decompression constitute the fundamental management principles.

The urgency of biliary decompression depends on disease severity; all patients who fail to improve or deteriorate within 12 to 24 hours of instituting medical therapy (i.e., supportive care and antibiotic therapy) should undergo immediate biliary decompression by either endoscopic (see Chapters 20 and 30 ) or percutaneous (see Chapters 31 and 52 ) approaches based on the type and suspected location of the obstruction in the biliary tree. A distal biliary tree obstruction is best decompressed endoscopically, whereas obstructions proximal to the hepatic bifurcation or from biliary-enteric anastomoses should be decompressed percutaneously in most situations. Procedures to achieve goals beyond decompression, such as papillotomy, balloon stricture dilation, or biliary tract debris clearance, should be avoided in the setting of recent or present sepsis. Operative biliary decompression should be reserved only for those patients who fail nonoperative decompression, as it is associated with high morbidity and mortality. The extent of operative biliary decompression, should, in most cases, be limited to T-tube type decompression of the common bile duct (CBD) with definitive management of the underlying cause of the biliary obstruction deferral until the patient’s condition has improved. Continuation of antibiotic therapy should be guided by the persistence of residual biliary obstruction because of the increased risk of recurrent cholangitis.

An international consensus on evidence-based care for patients with cholangitis was first published in 2007 as the Tokyo Guidelines (TG) and was subsequently updated in 2013 (TG13) and 2018 (TG18). These guidelines are referenced throughout this chapter.

Cholangitis presents along a spectrum of severity ranging from mild, intermittent, and recurrent episodes of fever, jaundice, and abdominal pain, as described by Charcot in 1877, to rapidly progressive systemic illness that results in shock, mental status changes, and death. The pathogenesis of cholangitis involves (1) obstruction of bile flow, (2) elevation of intraductal biliary pressure, (3) colonization of bile with microorganisms, and (4) translocation of bacteria into the vascular and lymphatic system, with a subsequent systemic inflammatory response that can progress to life-threatening sepsis. Complications include hepatic abscesses, recurrent cholangitis, and secondary biliary cirrhosis.

The most common causes of biliary obstruction are choledocholithiasis (see Chapter 37 ), neoplasia (see Chapters 49 , 51 , 62 , and 63 ), and occluded biliary stents. Other notable causes ( Box 43.1 ) include benign biliary strictures (see Chapter 42 ), conditions that cause extrinsic compression of the bile duct, parasites, and inflammatory/immune-mediated syndromes.

BOX 43.1

Adapted from Kimura Y, et al. TG13 current terminology, etiology, and epidemiology of acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci. 2013 Jan;20(1):8–23.

AIDS, Acquired immunodeficiency syndrome; ERCP, endoscopic retrograde cholangiopancreatography; PTC, percutaneous transhepatic cholangiography.

Causes of Cholangitis

1.
Biliary stones
- a.
  Choledocholithiasis
- b.
  Hepatolithiasis
- c.
  Mirizzi syndrome
2.
Benign biliary strictures
- a.
  Congenital factors
- b.
  Biliary surgery
  - i.
    Damaged bile duct
  - ii.
    Strictured choledochojejunostomy
- c.
  Chronic pancreatitis
- d.
  Primary sclerosing cholangitis
- e.
  Orthotopic liver transplantation
- f.
  Cholangiopathy in patients with AIDS
3.
Malignant biliary obstruction
- a.
  Pancreas
- b.
  Bile duct/gallbladder
- c.
  Ampulla
- d.
  Duodenum
4.
Nonsurgical biliary interventions
- a.
  ERCP
- b.
  PTC
- c.
  Biliary stents
5.
Parasitic infection
6.
Miscellaneous

Diagnosis

Biliary infection is suspected in patients who present with any combination of fever, chills (often severe rigors), abdominal pain, jaundice, nausea, vomiting, or altered mental status. A detailed medical history is obtained with specific attention to constitutional symptoms, gallstone or biliary disease, malignancy, autoimmune disease, prior biliary interventions, and prior abdominal surgery. A thorough physical examination is undertaken in which the presence or absence of altered mental status, jaundice, focal or generalized abdominal tenderness, and peritonitis are noted. Vital signs should be measured, and the situation is deemed urgent when significant hemodynamic changes are present. Laboratory testing includes complete blood count (CBC) with platelet count and differential, basic metabolic panel (BMP), and hepatic function panel. When feasible, blood cultures should be drawn in the presence of fever, rigors, or before empiric antimicrobial administration. Arterial blood gas analysis is indicated in patients with hemodynamic instability, respiratory insufficiency, alterations in mental status, or when other laboratory testing suggests the presence of organ dysfunction. In terms of diagnostic imaging, abdominal ultrasound and computed tomography (CT) imaging are useful first-line studies for detecting biliary obstruction.

The diagnosis of cholangitis based on the Charcot’s triad (fever, right upper quadrant abdominal pain, and jaundice) or Reynaud’s pentad (the Charcot’s triad plus lethargy and hypotension) provides high specificity but low sensitivity. More updated diagnostic criteria are provided by TG, which are based on several multicenter outcomes studies and establish a common definition and diagnostic criteria ( Box 43.2 ) that incorporates clinical, laboratory, and imaging findings. Given the importance of early recognition and treatment, these diagnostic criteria prioritize sensitivity over specificity, providing an overall accuracy of 90% to diagnose cholangitis. Although not included in the criteria, the presence of abdominal pain and history of biliary disease or previous biliary instrumentation are helpful adjunct factors. Acute cholecystitis and acute hepatitis represent common etiologies and must be considered in the differential diagnosis.

BOX 43.2

Adapted from Kiriyama S, et al. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos). J Hepatobiliary Pancreat Sci. 2018;25(1):17–30.

PT-INR, Prothrombin time-international normalized ratio; WBC, white blood cell count.

Tokyo Guidelines Criteria for Acute Cholangitis

Diagnostic criteria

A.
Systemic Inflammation
- A-1.
  Fever (>38°C) and/or shaking chills
- A-2.
  Laboratory evidence of inflammatory response (WBC <4 or >10, C-reactive protein >1)
B.
Cholestasis
- B-1.
  Jaundice (total bilirubin >2 mg/dL)
- B-2.
  Abnormal liver function tests
C.
Imaging
- C-1.
  Biliary dilatation
- C-2.
  Imaging evidence of biliary obstruction

Suspected diagnosis: one item in A + one item in either B or C.

Definite diagnosis: one item in A, one item in B, and one item in C.

Severity grading

Grade III (severe) acute cholangitis – acute cholangitis associated with the onset of dysfunction in at least one of the following organs/systems:

1.
Cardiovascular dysfunction: hypotension requiring dopamine ≥5 lg/kg per min, or any dose of norepinephrine
2.
Neurologic dysfunction: disturbance of consciousness
3.
Respiratory dysfunction: PaO ₂ /FiO ₂ ratio <300
4.
Renal dysfunction: oliguria, serum creatinine >2.0 mg/dL
5.
Hepatic dysfunction: PT-INR >1.5
6.
Hematologic dysfunction: platelet count <100,000/mm ³

Grade II (moderate) acute cholangitis - acute cholangitis associated with any two of the following conditions:

1.
Abnormal WBC count (>12,000 cells/mm ³ , <4000 cells/mm ³ )
2.
High fever (≥39°C)
3.
Age (≥75 years old)
4.
Hyperbilirubinemia (total bilirubin ≥5 mg/dL)
5.
Hypoalbuminemia

Grade I (mild) acute cholangitis - acute cholangitis that does not meet the criteria of “grade III (severe)” or “grade II (moderate)” acute cholangitis at initial diagnosis. Early diagnosis, early biliary drainage and/or treatment for etiology, and antimicrobial administration are fundamental for all grades of acute cholangitis.

In addition to providing a standardized diagnostic approach, TG also established a prognostic severity grading system based on clinical and laboratory parameters (see Box 43.2 ): a large retrospective study ( n = 7294) found mortality rates of 2.4%, 4.7%, and 8.4% for TG18 severity grades I (mild), II (moderate), and III (severe), respectively. Furthermore, this study noted a significantly lower 30-day mortality in patients with grade II disease who were treated with biliary decompression within 24 to 48 hours, suggesting that TG18 severity grading may be useful for identifying patients most likely to benefit from early biliary drainage. Nonetheless, biliary decompression/drainage should be performed for any patients regardless of severity grade who do not respond to initial supportive care and antimicrobial therapy.

Imaging studies

Noninvasive imaging modalities to visualize the biliary tree and gallbladder include transabdominal ultrasound, CT, magnetic resonance cholangiopancreatography (MRCP; see Chapter 16 ), and radionuclide imaging (e.g., hepatobiliary iminodiacetic acid [HIDA] scan; see Chapter 17 ). Nonoperative invasive modalities requiring sedation and/or local or general anesthesia include endoscopic ultrasonography (EUS; see Chapter 22 ), intraductal ultrasonography (IDUS), endoscopic retrograde cholangiopancreatography (ERCP; see Chapters 20 and 30 ), and percutaneous transhepatic cholangiopancreatography (PTC; see Chapters 31 and 52 ). The most widely used initial diagnostic imaging test remains a contrast-enhanced CT scan of the abdomen and pelvis.

Transabdominal ultrasound

Transabdominal ultrasound is the preferred first-line imaging study when evaluating a patient with suspected cholangitis due to its low cost, wide availability, and lack of ionizing radiation. Ultrasound can reliably detect the presence of intrahepatic and extrahepatic biliary dilation with a sensitivity of 85% to 95%. It is important to note that biliary dilation may be absent in acute obstruction, as this takes time to develop. Transabdominal ultrasound has limited sensitivity, however, for detecting choledocholithiasis, particularly small stones or lesions in the distal CBD that are often obscured by bowel gas. The sensitivity of ultrasound to detect CBD stones varies between 20% and 75%, with increased sensitivity in the case of multiple large stones within a dilated CBD and less sensitivity in the case of stone impaction in the retropancreatic segment of the CBD.

Computed tomography

CT imaging overcomes the technical limitations of ultrasound and can accurately detect biliary obstruction and characterize the cause of biliary stenosis. In cholangitis, contrast-enhanced CT may reveal bile duct thickening and enhancement (see Chapter 16 ). The arterial phase may reveal inhomogeneous enhancement of hepatic parenchyma. Findings of biliary ductal dilatation or abrupt termination of the CBD are indirect findings in choledocholithiasis. However, because up to 24% of gallstones have the same density as bile, the sensitivity of CT for detecting CBD stones ranges from 25% to 90%. CT can also detect complications of cholangitis, including hepatic abscess ( Fig. 43.1 ) and pylephlebitis (suppurative thrombosis of the portal vein). Due to its availability and convenience, CT imaging may be completed ahead of transabdominal ultrasound or magnetic resonance imaging (MRI) when other abdominal pathologies are considered in the differential diagnosis. A key drawback of CT is the risk of nephrotoxicity associated with the use of contrast material, particularly in under resuscitated or hemodynamically unstable patients.

FIGURE 43.1, Abdominal computed tomographphy (CT) scan demonstrating a hepatic abscess involving the right hepatic lobe with surrounding inflammatory changes.

Magnetic resonance cholangiopancreatography

MRCP provides noninvasive three-dimensional (3D) imaging of the biliary tree using a heavily T2-weighted scheme that emphasizes the intensity of stationary fluids (see Chapter 16 ). It outperforms both ultrasound and CT in its ability to delineate the bile duct and identify both malignant disease and CBD stones causing obstruction. In a systematic review, the sensitivity and specificity of MRCP for the detection of choledocholithiasis were 93% and 96%, respectively. MRCP cannot differentiate stones from air bubbles, sludge, or blood clots, as all of these lack liquid. Furthermore, MRCP cannot detect stones less than 3 mm in size, nor can it detect impacted stones in the ampulla, which require evaluation of T1 images before and after gadolinium injection. The drawbacks of MRCP are cost, limited accessibility, and specific contraindications, such as morbid obesity and metallic foreign bodies/devices. Therefore MRCP is typically reserved for cases in which diagnosis proves difficult with ultrasound or CT.

Endoscopic ultrasound

EUS can provide additional diagnostic information and allows therapeutic intervention (see Chapter 22 ). Once endoscopically passed through the stomach and into the duodenum, the ultrasound probe is in close proximity to the CBD. By using high-frequency ultrasound (7.5–12 MHz), the resolution of EUS is exceptional (<1 mm), and allows accurate detection of small gallstones or other obstructive etiologies. EUS has a sensitivity approaching 100% and a specificity of greater than 90%, with an overall accuracy of 96% to detect bile duct stones. EUS can be combined with fine-needle aspiration to provide tissue diagnosis or ERCP during the same session if clinically warranted. The major limitations of endoscopic techniques are that they cannot be performed in patients with altered anatomy, such as those with a prior distal gastrectomy or gastric bypass, or in the presence of a significantly calcified pancreas or hilar biliary pathology.

Intraductal ultrasonography

IDUS can be performed endoscopically or percutaneously by introducing a flexible, thin-caliber (2-mm) ultrasound probe into the biliary and/or pancreatic ducts using wire guidance. IDUS utilizes high-frequency ultrasound (12.30 MHz) to provide high resolution (0.07–0.018 mm) at the cost of decreased depth of penetration (2–3 cm). Specialized centers have reported the cannulation rate of the major papilla to approach 100%, obviating the need for sphincterotomy in most cases. In addition, IDUS may identify lesions missed by traditional imaging, making it a useful adjunct to ERCP for the identification and characterization of bile duct lesions. Drawbacks include the need for specialized equipment, cost, and operator expertise.

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