Recommendations

Key Recommendations

Biliary pain, the most common symptom of cholelithiasis, results from either obstruction of the cystic duct or from obstruction and/or passage of a gallstone through the common bile duct. Biliary pain, cholecystitis, cholangitis, or pancreatitis develop annually in 1% to 2% of those with asymptomatic cholelithiasis.[1][2][9][14][15][16][17]

Features of cholecystitis, cholangitis, or pancreatitis may clinically overlap; therefore, accurate diagnostic imaging is critical. In addition to standard laboratory evaluation, the initial radiographic test of choice for symptomatic cholelithiasis is a transabdominal ultrasound.[71][72] Subsequent imaging choice depends on the index of clinical suspicion for complications of cholelithiasis.

History

Typical biliary pain (biliary colic) occurs in the right upper quadrant or epigastric area, sometimes after the consumption of food, often around 1 hour after eating, particularly in the evening or at night time.[73] This constant pain increases in intensity and lasts for several hours. Pain of short duration (<30 minutes) is not biliary colic, while that of long duration (over 5 hours) suggests cholecystitis or another major complication.[1] Pain may be accompanied by nausea.[1]

Risk factors should be identified; these include a positive family history, obesity, diabetes, metabolic syndrome, use of certain drugs (e.g., octreotide, glucagon-like peptide-1 receptor agonists, ceftriaxone), terminal ileum disease, pregnancy, cirrhosis, and hemolytic anemia (e.g., sickle cell anemia or thalassemia).[4][5][21][22][50][52][53]

Physical exam

Physical exam is focused on identifying signs of any complications of cholelithiasis. Murphy's sign (inspiratory arrest when palpating the gallbladder fossa) is the most common abdominal exam feature in patients with symptomatic cholelithiasis.[1] It has a high sensitivity (97%) but poor specificity (48%) for acute cholecystitis.[74] Dyspepsia, heartburn, flatulence, and bloating are common, but are not characteristic for gallstone disease.[1][2]

Fever suggests a complication such as acute cholecystitis. Jaundice is rare in simple acute cholecystitis, being more suggestive of a stone in the common duct, cholangitis, or pancreatitis.[31][75]

Laboratory testing

Complete blood count and liver biochemistry are usually normal with an episode of simple biliary pain.

  • An elevated white blood cell count suggests acute cholecystitis, cholangitis, or pancreatitis.[1][31] See Acute cholecystitis and Acute cholangitis.

  • Obstructive choledocholithiasis is commonly associated with deranged liver function tests; specifically, elevated alkaline phosphatase and elevated bilirubin.

  • Brief biliary obstruction with subsequent stone passage causes an early, transient elevation in alanine aminotransferase before the alkaline phosphatase rises.[76]

Patients who present with severe sudden-onset mid-epigastric or left upper quadrant abdominal pain (with or without radiation to the back) should have serum lipase levels taken to exclude pancreatitis.[1] See Acute pancreatitis.

  • Serum lipase and amylase have similar sensitivity and specificity, but lipase levels remain elevated for longer (up to 14 days after symptom onset vs. 5 days for amylase), providing a higher likelihood of picking up the diagnosis in patients with a delayed presentation.[77][78]

Abdominal ultrasound

The initial imaging test of choice in patients with suspected biliary pain is abdominal ultrasound to detect gallbladder stones or bile duct dilation caused by biliary obstruction.[1][71][72][79][80] If the history and exam, laboratory test results, and ultrasound findings are in agreement, no further imaging is needed.[81]

  • If available, targeted point of care ultrasound (POCUS), performed at the bedside, can help to diagnose gallstones and expedite subsequent clinical decision making.[71][72][82][83]

  • Abdominal ultrasound, however, has low sensitivity for choledocholithiasis, despite being accurate in identifying any associated bile duct dilation.[84][85]

  • For acute calculous cholecystitis, abdominal ultrasound has high sensitivity for detecting stones, as well as distension of the gallbladder lumen, plus any inflammatory features, gallbladder wall thickening, pericholecystic fluid, and/or a positive radiologic Murphy's sign.[84]

[Figure caption and citation for the preceding image starts]: Ultrasound of acute cholecystitis and presence of gallstones: the arrow points to a gallstone in the fundus of the gallbladder with its echogenic shadow belowCourtesy of Charles Bellows and W. Scott Helton; used with permission [Citation ends].Ultrasound of acute cholecystitis and presence of gallstones: the arrow points to a gallstone in the fundus of the gallbladder with its echogenic shadow below[Figure caption and citation for the preceding image starts]: Gallbladder ultrasound demonstrating cholelithiasis with characteristic shadowingCourtesy of Kuojen Tsao; used with permission [Citation ends].Gallbladder ultrasound demonstrating cholelithiasis with characteristic shadowing

Subsequent imaging

Further imaging may be required based on the clinical characteristics and associated index of clinical suspicion for complications.

  • If choledocholithiasis is suspected (e.g., dilated bile ducts or abnormal liver biochemistry), magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound scan (EUS) is warranted.[75][84]

  • MRCP has a sensitivity of 95% and specificity of 97% for the detection of bile duct stones.[75][86] However, it has a reduced sensitivity (65%) for the detection of small (<5 mm) biliary stones.[86][87]

  • EUS is similarly accurate for the detection of bile duct stones, especially in patients who are unable to undergo an MRCP (e.g., those with implanted devices). Depending on local expertise, EUS may be more accurate than MRCP, and can be useful for detecting patients at low to moderate risk of bile duct stones (negative imaging but positive symptoms and/or blood tests) who would benefit from a subsequent endoscopic retrograde cholangiopancreatography (ERCP).[1][20][88][89][90][91][92][93][94][95]

  • If initial imaging is negative but clinical features and/or blood tests are suggestive of choledocholithiasis and the patient is at high risk of complications (e.g., acute cholangitis, acute pancreatitis), ERCP is recommended. ERCP can be both diagnostic and therapeutic, enabling removal of any obstructing stones to provide biliary drainage.[94] [ Cochrane Clinical Answers logo ] [Evidence B]

  • An unremarkable abdominal ultrasound in the presence of biliary pain may warrant an abdominal computed tomography scan to evaluate for alternative diagnoses (e.g., acute cholangitis or gallstone pancreatitis) and to identify potential complications of acute cholecystitis (e.g., emphysema of the gallbladder wall, abscess formation, perforation).[1][79][95]

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