Abstract: 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. 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.

Plain-language summary: 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. 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. All the studies were of low methodological quality, which may undermine the validity of our findings. Further studies of high methodological quality are necessary.