Background
Bile, produced in the liver and stored temporarily in the gallbladder, is released into the small bowel on eating fatty food. The common bile duct is the tube through which bile flows from the gallbladder to the small bowel. Stones in the common bile duct (common bile duct stones), usually formed in the gallbladder before migration into the bile duct, can obstruct the flow of bile leading to jaundice (yellowish discolouration of skin, white of the eyes, and dark urine); infection of the bile (cholangitis); and inflammation of the pancreas (pancreatitis), which can be life threatening. Various diagnostic tests can be performed for the diagnosis of common bile duct stones. Depending upon the availability of resources, these stones are removed endoscopically (usually the case) or may be removed as a part of the operation performed to remove the gallbladder (it is important to remove the gallbladder since the stones continue to form in the gallbladder and can cause recurrent problems). Non-invasive tests such as ultrasound (use of sound waves higher than audible range to differentiate tissues based on how they reflect the sound waves) and blood markers of bile flow obstruction such as serum bilirubin and serum alkaline phosphatase are used to identify people at high risk of having common bile duct stones. Using non-invasive tests means that only those people at high risk can be subjected to further tests. We reviewed the evidence on the accuracy of ultrasound and liver function tests for detection of common bile duct stones. The evidence is current to September 2012.
Study characteristics
We identified five studies including 523 participants that reported the diagnostic test accuracy of ultrasound. One of these studies, involving 262 participants, also reported the diagnostic test accuracy of serum bilirubin and serum alkaline phosphatase. All the studies included people with symptoms. One study included only participants who had not undergone previous cholecystectomy (removal of gallbladder). This information was not available from the remaining studies.
Key results
Based on an average sensitivity of 73% for ultrasound, we would expect that on average 73 out of 100 people with common bile duct stones will be detected while the remaining 27 people will be missed and will not receive appropriate treatment. The average number of people with common bile duct stones detected using ultrasound may vary between 44 and 90 out of 100 people. Based on an average specificity of 91% for ultrasound, we would expect that on average 91 out of 100 people without common bile duct stones would be identified as not having common bile duct stones; 9 out of 100 would be false positives and not receive appropriate treatment. The average number of false positives could vary between 5 and 16 out of 100 people.
Evidence from one study suggested that using a level of serum alkaline phosphatase higher than 125 units to distinguish between people who have and people who do not have common bile duct stones gave better diagnostic accuracy than using a level twice the normal limit (which usually ranges between 0 and 40). The study also showed better accuracy for serum alkaline phosphatase compared to serum bilirubin.
The sensitivity of serum alkaline phosphatase at the 125 units cut-off was 92%, which means that 92 out of 100 people with common bile duct stones would be detected but 8 out of 100 people will be missed. The number detected could vary between 74 and 99 out of 100 people. Based on the specificity of 79%, 79 out of 100 people without common bile duct stones will be correctly identified as not having common bile duct stones while the remaining 21 people will be false positives. The number of false positives could vary between 16 and 26 out of 100 people. This suggests that further non-invasive tests may be useful to diagnose common bile duct stones prior to the use of invasive tests.
Quality of evidence
All the studies were of low methodological quality, which may undermine the validity of our findings.
Future research
Further studies of high methodological quality are necessary.
Many people may have common bile duct stones in spite of having a negative ultrasound or liver function test. Such people may have to be re-tested with other modalities if the clinical suspicion of common bile duct stones is very high because of their symptoms. False-positive results are also possible and further non-invasive testing is recommended to confirm common bile duct stones to avoid the risks of invasive testing.
It should be noted that these results were based on few studies of poor methodological quality and the results for ultrasound varied considerably between studies. Therefore, the results should be interpreted with caution. Further studies of high methodological quality are necessary to determine the diagnostic accuracy of ultrasound and liver function tests.
Ultrasound and liver function tests (serum bilirubin and serum alkaline phosphatase) are used as screening tests for the diagnosis of common bile duct stones in people suspected of having common bile duct stones. There has been no systematic review of the diagnostic accuracy of ultrasound and liver function tests.
To determine and compare the accuracy of ultrasound versus liver function tests for the diagnosis of common bile duct stones.
We searched MEDLINE, EMBASE, Science Citation Index Expanded, BIOSIS, and Clinicaltrials.gov to September 2012. We searched the references of included studies to identify further studies and systematic reviews identified from various databases (Database of Abstracts of Reviews of Effects, Health Technology Assessment, Medion, and ARIF (Aggressive Research Intelligence Facility)). We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively.
We included studies that provided the number of true positives, false positives, false negatives, and true negatives for ultrasound, serum bilirubin, or serum alkaline phosphatase. We only accepted studies that confirmed the presence of common bile duct stones by extraction of the stones (irrespective of whether this was done by surgical or endoscopic methods) for a positive test result, and absence of common bile duct stones by surgical or endoscopic negative exploration of the common bile duct, or symptom-free follow-up for at least six months for a negative test result as the reference standard in people suspected of having common bile duct stones. We included participants with or without prior diagnosis of cholelithiasis; with or without symptoms and complications of common bile duct stones, with or without prior treatment for common bile duct stones; and before or after cholecystectomy. At least two authors screened abstracts and selected studies for inclusion independently.
Two authors independently collected data from each study. Where meta-analysis was possible, we used the bivariate model to summarise sensitivity and specificity.
Five studies including 523 participants reported the diagnostic accuracy of ultrasound. One studies (262 participants) compared the accuracy of ultrasound, serum bilirubin and serum alkaline phosphatase in the same participants. All the studies included people with symptoms. One study included only participants without previous cholecystectomy but this information was not available from the remaining studies. All the studies were of poor methodological quality. The sensitivities for ultrasound ranged from 0.32 to 1.00, and the specificities ranged from 0.77 to 0.97. The summary sensitivity was 0.73 (95% CI 0.44 to 0.90) and the specificity was 0.91 (95% CI 0.84 to 0.95). At the median pre-test probability of common bile duct stones of 0.408, the post-test probability (95% CI) associated with positive ultrasound tests was 0.85 (95% CI 0.75 to 0.91), and negative ultrasound tests was 0.17 (95% CI 0.08 to 0.33).
The single study of liver function tests reported diagnostic accuracy at two cut-offs for bilirubin (greater than 22.23 μmol/L and greater than twice the normal limit) and two cut-offs for alkaline phosphatase (greater than 125 IU/L and greater than twice the normal limit). This study also assessed ultrasound and reported higher sensitivities for bilirubin and alkaline phosphatase at both cut-offs but the specificities of the markers were higher at only the greater than twice the normal limit cut-off. The sensitivity for ultrasound was 0.32 (95% CI 0.15 to 0.54), bilirubin (cut-off greater than 22.23 μmol/L) was 0.84 (95% CI 0.64 to 0.95), and alkaline phosphatase (cut-off greater than 125 IU/L) was 0.92 (95% CI 0.74 to 0.99). The specificity for ultrasound was 0.95 (95% CI 0.91 to 0.97), bilirubin (cut-off greater than 22.23 μmol/L) was 0.91 (95% CI 0.86 to 0.94), and alkaline phosphatase (cut-off greater than 125 IU/L) was 0.79 (95% CI 0.74 to 0.84). No study reported the diagnostic accuracy of a combination of bilirubin and alkaline phosphatase, or combinations with ultrasound.