Acalculous Biliary Pain

ByYedidya Saiman, MD, PhD, Lewis Katz School of Medicine, Temple University
Reviewed/Revised Aug 2023
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Acalculous biliary pain is biliary colic without gallstones, resulting from structural or functional disorders; it is sometimes treated with laparoscopic cholecystectomy or endoscopic sphincterotomy.

(See also Overview of Biliary Function.)

Biliary colic can occur in the absence of gallstones, particularly in young women. Acalculous biliary pain can lead to laparoscopic cholecystectomy in some patients. Common causes of such biliary pain include the following:

  • Microscopic stones (biliary sludge)—not detected by routine abdominal ultrasonography

  • Abnormal gallbladder emptying (gallbladder dyskinesia)

  • Biliary tract hypersensitivity

  • Sphincter of Oddi dysfunction (including papillary stenosis and functional gallbladder, biliary sphincter, or pancreatic sphincter disorders [1])

  • Hypersensitivity of the adjacent duodenum

  • Gallstones that have spontaneously passed

General reference

  1. 1. Cotton PB, Elta GH, Carter AR, et al: Gallbladder and sphincter of Oddi disorders. Gastroenterology S0016-5085(16)00224-9, 2016. doi: 10.1053/j.gastro.2016.02.033

Diagnosis of Acalculous Biliary Pain

  • Usually ultrasonography and sometimes endoscopic retrograde cholangiopancreatography (ERCP) with sphincter of Oddi manometry

The best diagnostic approach remains unclear.

Acalculous biliary pain is suspected in patients with biliary colic when diagnostic imaging cannot detect gallstones. Imaging should include ultrasonography and, where available, endoscopic ultrasonography (for small stones < 1 cm).

Abnormal laboratory tests may reveal evidence of a biliary tract abnormality (eg, elevated alkaline phosphatase, bilirubin, alanine aminotransferase, or aspartate aminotransferase) or a pancreatic abnormality (eg, elevated lipase) during an episode of acute pain. Cholescintigraphy with cholecystokinin infusion measures gallbladder emptying (ejection fraction); potentially interfering drugs such as calcium channel blockers, opioids, and anticholinergics should not be used. ERCP with biliary manometry detects papillary stenosis and sphincter of Oddi dysfunction.

Sphincter of Oddi dysfunction (functional gallbladder disorder, functional biliary sphincter disorder, and functional pancreatic sphincter disorder)—characterized by functional acalculous biliary pain—is diagnosed according to the Rome IV criteria (1). All of the following criteria must be met:

  • Pain occurs in the epigastrium and/or right upper quadrant.

  • Symptoms recur at different intervals.

  • Pain increases to a steady degree and lasts 30 minutes or longer.

  • Pain is severe enough to interrupt daily activities or lead to an emergency department visit.

  • Pain is not significantly related to bowel movements.

  • Pain is not significantly relieved by postural change or acid suppression.

Supportive criteria include:

  • Pain with nausea and/or vomiting

  • Pain that radiates to the back and/or right infrascapular region

  • Pain that interrupts sleep 

A functional gallbladder disorder is diagnosed when the Rome IV criteria are met, in the absence of cholelithiasis or a structural etiology of the pain. Typically, scintigraphy is abnormal or gallbladder ejection fraction is decreased.

A functional biliary sphincter of Oddi disorder is diagnosed when the Rome IV criteria are met, in the absence of cholelithiasis or a structural etiology to the pain, plus elevated aminotransferases or a dilated common bile duct (but not both). Typically, serum pancreatic tests are normal, sphincter of Oddi manometry may be abnormal, and scintigraphy may be abnormal.

A functional pancreatic sphincter of Oddi disorder is diagnosed when the Rome IV criteria are met in patients with a history of recurrent idiopathic episodes of acute pancreatitis (typical pain with amylase or lipase >3 times normal and/or imaging evidence of acute pancreatitis) plus no clear etiology, with negative endoscopic ultrasound imaging, and with abnormal sphincter of Oddi manometry.

Diagnosis reference

  1. 1. Cotton PB, Elta GH, Carter AR, et al: Rome IV. Gallbladder and sphincter of Oddi disorders. Gastroenterology S0016-5085(16)00224-9, 2016. doi: 10.1053/j.gastro.2016.02.033

Treatment of Acalculous Biliary Pain

  • Unclear but sometimes laparoscopic cholecystectomy or endoscopic sphincterotomy

Laparoscopic cholecystectomy improves outcomes for patients with microscopic stones and possibly abnormal gallbladder motility. Otherwise, the role of laparoscopic cholecystectomy or endoscopic sphincterotomy remains unclear. Pharmacologic therapies have no proven benefit.

General reference

  1. 1. Cotton PB, Elta GH, Carter CR, et al: Gallbladder and sphincter of Oddi disorders. Gastroenterology 150(6):1420-1249.e2, 2016. doi:10.1053/j.gastro.2016.02.033

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