Background 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. Objectives To determine and compare the accuracy of ultrasound versus liver function tests for the diagnosis of common bile duct stones. Search methods 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. Selection criteria 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. Data collection and analysis Two authors independently collected data from each study. Where meta-analysis was possible, we used the bivariate model to summarise sensitivity and specificity. Main results 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 mu mol/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 mu mol/L) was 0.84 (95% CI 0.64 to 0.95), and alkaline phosphatase (cutoff 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 mu mol/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. Authors' conclusions 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.
