Criteria for risk stratification proposed by the American Society of Gastrointestinal Endoscopy (ASGE) are frequently used worldwide. Following ASGE guidelines in 2010, patients are routinely categorized according to the probability of choledocolithiasis in low risk (<10%), intermediate risk (10%-50%) and high risk (>50%) . Patients with intermediate risk benefit from additional biliary imaging [18,19] and options for this include magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS) and intraoperative cholangiography (IOC) . In their updated guidelines of 2019, ASGE suggests either EUS or MRCP to confirm choledocolithiasis in intermediate risk patients . The differences between both classifications change the risk in 6 of our patients as described in Table 7.
Moreover, the wide range of imaging studies paired with their varying sensitivity and specificity, has enriched the discussion regarding subsequent steps after intermediate risk classification. Meeralam et al. published a meta-analysis comparing EUS and MRCP diagnostic accuracy in which, albeit cost effectiveness and adverse events were not taken into consideration, MRCP provided good diagnostic accuracy with a sensitivity and specificity of 87% and 92% respectively . By protocol and availability at our institution, patients with intermediate risk for choledocolithiasis are assessed by MRCP. From 327 MRCP performed in this study, up to 24,9% were positive for choledocolithiasis. Toro-Calle et al, found a choledocolithiasis frequency of 26.6% in patients with intermediate risk, which is comparable with our results . It is worth noting that the seemingly low frequency of choledocolithiasis in this group of patients may be related to lower sensitivity (33% to 71%) of MRCP in the setting of small stones (<3mm) [23,24], which was present in up to 4.72% of our patients according to US findings. Yet, Badger et al found that most of the patients that underwent MRCP were followed with a more invasive test in 82% of cases, increasing the conflicting findings among literature .
Liver chemistries are measured as indirect markers of hepatobiliary disease , standard markers include AST, ALT, alkaline phosphatase and bilirubin as moderate predictors of choledocolithiasis in ASGE guidelines . Aminotransferases including AST and ALT are enzymes involved in the transfer of amino groups of aspartate and alanine to ketoglutaric acid and referred to as transaminases ; regarding this predictors for intermediate risk, there is inconsistency in literature findings, some studies have shown that gamma glutamyl transferase (GGT) has the highest sensitivity, others demonstrate superiority in ALT for choledocolithiasis . In our institution, median values of total bilirubin and alkaline phosphatase were within normal limits, whereas median values of transaminases were approximately 3 times over cutoff level; GGT levels were not measured. AST and ALT were elevated more than threefold in at least 50% of patients with choledocolithiasis; nonetheless no statistical significance correlation was found. Zare et al, in a prospective study performed in 350 patients for the assessment of liver function tests in the diagnosis of common bile duct stones in patients with cholecystitis found ALT as an independent predictor of cholelithiasis (OR: 2; P=0.04) . More recently, novel predictive scores are being proposed showing AUC of 0.77 and 0.76 for AST and ALT respectively in a cohort of 1089 patients . Other descriptive studies have shown AST as the least sensitive parameter altered approximately 50.8% of times . Thus, despite the discrepancy of liver enzyme specificity, ongoing elevation of liver tests can provide support on deciding further imaging studies .
Common bile duct (CBD) stones should be diagnosed on time, despite the lack of a consensus on the usefulness of liver enzymes measurement as in CBD stones; multiple studies suggest a positive association between: Alkaline phosphatase, alanine transaminase (ALT) and choledocolithiasis . Isherwood et al, described the association between choledocolithiasis and echographic finding of common bile duct dilation more than 6 mm OR 3.16 (p=0.06), and elevated values of alkaline phosphatase OR 4.64 (p<0.00), and alanine transaminase (OR 5.40 p<0.001). Nonetheless, despite in our study CBD dilation had an increased odds ratio (12,48 IC 3.97 - 39.18), transaminases did not show an statistically significant relationship as a diagnosis predictor.
Finally, our results and the comparison with the literature, shows the complexity in the diagnosis process, with important covariates that could mislead a timely diagnosis, and could delay the surgical management of cholelithiasis; these exposes the need of more specific and sensible predictive tools for CBD stones.
Among limitations of this study are its retrospective nature, the lack of stronger associations between the variables and the outcome and the scarcity of previous studies to compare our findings. Even though a considerable group of patients with cholelithiasis have concomitant intermediate choledocolithiasis the risk the scores available still give very loose recommendations regarding follow-up steps.