Article Search
검색
검색 팝업 닫기

Metrics

Help

  • 1. Aims and Scope

    Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE

  • 2. Editorial Board

    Editor-in-Chief + MORE

    Editor-in-Chief
    Yong Chan Lee Professor of Medicine
    Director, Gastrointestinal Research Laboratory
    Veterans Affairs Medical Center, Univ. California San Francisco
    San Francisco, USA

    Deputy Editor

    Deputy Editor
    Jong Pil Im Seoul National University College of Medicine, Seoul, Korea
    Robert S. Bresalier University of Texas M. D. Anderson Cancer Center, Houston, USA
    Steven H. Itzkowitz Mount Sinai Medical Center, NY, USA
  • 3. Editorial Office
  • 4. Articles
  • 5. Instructions for Authors
  • 6. File Download (PDF version)
  • 7. Ethical Standards
  • 8. Peer Review

    All papers submitted to Gut and Liver are reviewed by the editorial team before being sent out for an external peer review to rule out papers that have low priority, insufficient originality, scientific flaws, or the absence of a message of importance to the readers of the Journal. A decision about these papers will usually be made within two or three weeks.
    The remaining articles are usually sent to two reviewers. It would be very helpful if you could suggest a selection of reviewers and include their contact details. We may not always use the reviewers you recommend, but suggesting reviewers will make our reviewer database much richer; in the end, everyone will benefit. We reserve the right to return manuscripts in which no reviewers are suggested.

    The final responsibility for the decision to accept or reject lies with the editors. In many cases, papers may be rejected despite favorable reviews because of editorial policy or a lack of space. The editor retains the right to determine publication priorities, the style of the paper, and to request, if necessary, that the material submitted be shortened for publication.

Search

Search

Year

to

Article Type

Online first

Split Viewer

Online first

Predictors of Choledocholithiasis in Cholecystectomy Patients and Their Cutoff Values and Prediction Model in Korea in Comparison with the 2019 ASGE Guidelines

Jung Hun Woo1 , Hwanhyi Cho1 , Kihyun Ryu1 , Young Woo Choi1 , Sanghyuk Lee1 , Tae Hee Lee1 , Dae Sung Kim1 , In Seok Choi2 , Ju Ik Moon2 , Seung Jae Lee2

Departments of 1Gastroenterology and 2General Surgery, Konyang University Myunggok Medical Research Institute, Daejeon, Korea

Correspondence to: Kihyun Ryu
ORCID https://orcid.org/0000-0003-0595-6776
E-mail medidrug@kyuh.ac.kr

Jung Hun Woo and Hwanhyi Cho contributed equally to this work as first authors.

Received: December 20, 2023; Revised: February 9, 2024; Accepted: February 13, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gut Liver.

Published online May 7, 2024

Copyright © Gut and Liver.

Background/Aims: In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) established clinical predictors for choledocholithiasis. Our study was designed to evaluate these predictors within the Korean clinical context, establish cutoff values, and develop a predictive model.
Methods: This retrospective study analyzed patients who underwent laparoscopic cholecystectomy. The relationships between choledocholithiasis and predictors including age, blood tests, and imaging findings were assessed through univariate and multivariate logistic regression analyses. We established Korean cutoff values for these predictors and developed a scoring system for choledocholithiasis using a multivariate logistic regression. The performance of this scoring system was then compared with that of the 2019 ASGE guidelines through a receiver operating characteristic curve.
Results: We established Korean cutoff values for age (>70 years), alanine aminotransferase (>26.5 U/L), aspartate aminotransferase (>28.5 U/L), gamma-glutamyl transferase (GGT; >82.5 U/L), alkaline phosphatase (ALP; >77.5 U/L), and total bilirubin (>0.95 mg/dL). In the multivariate analysis, only age >70 years, GGT >77.5 U/L, ALP >77.5 U/L, and common bile duct dilatation remained significant. We then developed a new Korean risk stratification model from the multivariate analysis, with an area under the curve of 0.777 (95% confidence interval, 0.75 to 0.81). Our model was stratified into the low-risk, intermediate-risk, and high-risk groups with the scores being <1.0, 1.0–5.5, and >5.5, respectively.
Conclusions: Predictors of choledocholithiasis in cholecystectomy patients and their cutoff values in Korean should be adjusted and further studies are needed to develop appropriate guidelines.

Keywords: Choledocholithiasis, Cholecystectomy, Preoperative period

Cholecystitis refers to inflammation of the gallbladder that range from mild symptoms, such as abdominal pain, nausea, and vomiting, to severe conditions like septic shock or gallbladder perforation. The treatment of choice for this condition is cholecystectomy.1,2 Choledocholithiasis refers to the presence of gallstones in the bile duct system, the common bile duct (CBD) and the common hepatic duct, both of which are integral components of a shared pathway facilitating bile flow from the liver to the duodenum.3 Choledocholithiasis is found in 10% to 20% of patients with cholecystitis or symptomatic cholelithiasis, commonly occurs as a result of the movement of gallstones from the gallbladder.4,5 Predicting CBD stones before cholecystectomy is important in the prognosis of patients with cholecystitis.6 For several decades, endoscopic retrograde cholangiopancreatography (ERCP) was considered the gold standard for diagnosing CBD stones.7 When the gallbladder is removed, the storage space for bile is decreased, leading to increased pressure within the bile ducts. This can cause bile duct stones to move to the distal part and become impacted at the sphincter, resulting in pancreatitis or cholangitis. Prophylactic removal of these stones prior to surgery can prevent the occurrence of such adverse events.8 However, up to 6%–15% of patients undergoing ERCP are at risk for several complications, such as post-ERCP pancreatitis, duodenal perforation, and hemorrhage.9 Therefore, ERCP should be conducted for therapeutic purposes.10 In the 1990s, both endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP), which are low-risk diagnostic modalities, were introduced as alternative diagnostic modalities to ERCP for detecting CBD stones.11

In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) revised its clinical guidelines for diagnosing and managing patients with calculous cholecystitis or symptomatic cholelithiasis, using clinical predictors to identify risk groups for choledocholithiasis. These predictors include imaging study findings (e.g., the presence of CBD stones on ultrasonography), abnormal laboratory results (e.g., abnormal liver function tests or elevated total bilirubin levels of 4 mg/dL), and clinical symptoms (e.g., abdominal pain, fever, and jaundice).5 Recently, various studies had been conducted on whether the predictors presented in the ASGE guidelines are effective, and some studies argued that these predictors need adjustment.12

In Korea, few studies examined the clinical utility of the predictors recommended by the ASGE guidelines. Many centers often do not screen for preoperative choledocholithiasis in candidates according to ASGE guidelines, and cases are frequently identified passively after cholecystectomy due to increased biliary pressure causing cholangitis or pancreatitis. This study, conducted at a single center, screened all patients undergoing cholecystectomy for benign cholecystitis, assessing the suspicion of choledocholithiasis through preoperative evaluation, subsequently determining the necessity for ERCP based on these assessments. Our study aimed to evaluate the performance of ASGE’s clinical predictors within a Korean clinical context. We also sought to establish a cutoff value for these predictors and subsequently build a predictive model tailored to the Korean patient population, enhancing its clinical applicability and usefulness in everyday practice.

1. Study design

We conducted a single-center retrospective study at Konyang University Hospital in South Korea. This study received approval from the Institutional Review Board of Konyang University Medical Center (IRB number: 2022-10-002-007) and conformed to the principles of the Declaration of Helsinki and Good Clinical Practice. The informed consent was waived.

Patients who underwent laparoscopic cholecystectomy between January 2009 and March 2021 were included. Patient data such as age, sex, and five blood test types (alkaline phosphatase [ALP], aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transferase [GGT], and total bilirubin) were obtained from the medical records. We screened the majority of patients with acute cholecystitis planned for cholecystectomy using EUS or MRCP, in whom choledocholithiasis was not clearly observed on computed tomography or abdominal ultrasonography. Conversely, we excluded patients with liver cirrhosis, viral hepatitis, chronic alcoholism, biliary malignancy, and previous biliary tract intervention such as surgery or ERCP.

2. Predictors and outcomes

Factors associated with CBD stone predictors have been determined according to the 2019 ASGE guidelines for predictor identification. Predictive factors are divided into three main areas: age, blood test results, and imaging findings. The age is classified with a cutoff point at 55 years. For blood tests, particularly liver enzyme levels, exceeding the values of 110 U/L for ALP, 35 U/L for AST, 45 U/L for ALT,13 60 U/L for GGT, and 4.0 mg/dL for total bilirubin is considered abnormal.14 Regarding imaging, CT or ultrasound is used to assess whether CBD dilatation and CBD stones are present or absent. CBD dilatation refers to CBD size more than 6 mm.15 The primary outcome was the presence of a CBD stone, which is confirmed via procedures such as ERCP, MRCP, EUS, or surgery.

3. Statistical analysis

A univariate logistic regression analysis was conducted to calculate the odds ratio (OR) between predictors and presence of CBD stones, with 95% confidence intervals. Multivariable logistic regression analysis, assessing the impact of predictors on CBD stones in the presence of other risk factors, was the main statistical method for our Korean score model. Predictors were chosen using a backward stepwise method. The Korean threshold for CBD stone predictors, including age and liver enzyme levels, was established by receiver operating characteristic curve analysis. The threshold was set at the point where sensitivity and specificity were maximized. Continuous variables were analyzed using the Student t-test or Mann-Whitney U test, as appropriate. Categorial variables, such as sex and risk groups, were compared using the Pearson chi-square test or Fisher exact test. All statistical data were analyzed using the SPSS software (version 25.0; IBM Corp., Armonk, NY, USA), and p-values <0.05 were considered statistically significant.

4. Scoring system development and verification

The effectiveness of Korean cutoff values was evaluated by calculating the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and OR.

Based on these Korean cutoff values, a threshold-based model was constructed using a multivariable logistic regression. Significant predictors that contribute to the scoring system were selected through a backward stepwise method. We assigned scores according to the presence of these predictors using their logit coefficient values. The total score was distributed into 10% segments, from which we designated three risk groups: the high-risk group (cutoff score >90%), intermediate-risk group (cutoff score 10%–90%), and low-risk group (cutoff score <10%). The effectiveness of the Korean threshold-based model was evaluated by sensitivity, specificity, likelihood ratio positive, and likelihood ratio negative.

The performance of our model was evaluated using the area under the receiver operating characteristic curve (AUC). Following the TRIPOD statement’s suggestion for model comparisons, we compared our proposed model with an existing guideline. Considering that CBD stone scoring models deemed acceptable in our context are still unestablished, we selected the widely adopted 2019 version of the ASGE guideline, to be compared with our model.

1. Baseline characteristics

Among the 1,850 patients who underwent laparoscopic cholecystectomy for calculous cholecystitis or symptomatic cholelithiasis, 1,223 were included in the study after excluding those with incomplete medical records and those who met the exclusion criteria (n=627). Of these included patients, 277 were diagnosed with CBD stones, whereas 946 patients had no CBD stones (Fig. 1).

Figure 1.Study population flow diagram.

Table 1 shows patients’ baseline characteristics. The mean age was slightly higher in those with CBD stones than in those without CBD stones (68.52 years vs 62.50 years). The percentages of patients aged ≥55 years old were higher in the CBD stone group than in the group without CBD stones (76.5% vs 65.3%). The median results of the liver function test–ALP, AST, ALT, and GGT–in the CBD stone group were 106.0, 37.0, 41.0, and 224.0 U/L, whereas those in the group without CBD stones were 69.0, 23.5, 17.0, and 32.0 U/L, respectively. Regarding the total bilirubin levels, the former group had 1.18 mg/dL, whereas the latter group had 0.72 mg/dL.

Table 1. Distribution of Variables between Groups According to CBD Stone Status

VariableCBD stonep-value
Present (n=277)Absent (n=946)
Age, yr68.52±16.6062.50±16.88<0.001
Age >55 yr212 (76.5)618 (65.3)<0.001
Male sex168 (60.6)421 (44.5)<0.001
Liver function test
ALP, U/L106.0 (78.0–169.0)69.0 (55.0–97.0)
AST, U/L37.0 (24.0–82.0)23.5 (18.0–39.0)
ALT, U/L41.0 (16.0–163.0)17.0 (12.0–42.0)
Total bilirubin, mg/dL1.18 (0.72–1.80)0.72 (0.51–1.08)
GGT, U/L224 (56.0–451.5)32.0 (17.0–109.0)
CBD dilatation138 (49.8)33 (3.4)<0.001
Risk<0.001
High risk120 (43.3)10 (1.0)
Intermediate risk155 (56.0)750 (79.3)
Low risk2 (0.7)186 (19.7)
Diagnostic method0.125
MRCP164 (59.2)623 (65.9)
EUS16 (5.8)44 (4.7)
Preoperative ERCP264 (95.3)0

Data are presented as mean±SD, number (%), or median (interquartile range).

CBD, common bile duct; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; MRCP, magnetic resonance cholangiopancreatography; EUS, endoscopic ultrasonography; ERCP, endoscopic retrograde cholangiopancreatography.



2. Utility of CBD stone predictors

The sensitivity, specificity, PPV, NPV, and OR for CBD stone predictors were obtained according to the 2019 ASGE guideline and the Korean cutoff value.

1) According to 2019 ASGE guidelines

As shown in Table 2, the sensitivity, specificity, PPV, and NPV were 76.5%, 34.7%, 25.5%, and 83.5% for age >55 years; 59.2%, 68.4%, 35.4%, and 85.1% for ALT >35 U/L; and 5.8%, 98.9%, 61.5%, and 78.2% for total bilirubin >4 mg/dL and CBD dilatation, respectively.

Table 2. Effectiveness of Predictors for Choledocholithiasis Based on ASGE Guidelines

PredictorSensitivity, %Specificity, %Predictive value, %p-value
PositiveNegative
Age >55 yr76.534.725.583.5<0.001
ALP >110 U/L48.081.443.084.2<0.001
AST >45 U/L42.678.937.182.4<0.001
ALT >35 U/L59.268.435.485.1<0.001
GGT >60 U/L73.667.039.589.7<0.001
TB >4 + CBD dilatation5.898.961.578.2<0.001

ASGE, American Society for Gastrointestinal Endoscopy; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct.



In the univariable logistic regression analysis, Table 3 shows that the OR was 1.731 (95% confidence interval [CI], 1.272 to 2.357) for age >55 years, 4.041 (95% CI, 3.033 to 5.384) for ALP >110 U/L, 2.768 (95% CI, 2.082 to 3.680) for AST >45 U/L, 3.140 (95% CI, 2.383 to 4.139) for ALT >35 U/L, 5.679 (95% CI, 4.208 to 7.663) for GGT >60 U/L, and 5.738 (95% CI, 2.573 to 12.794) for total bilirubin >4 mg/dL with CBD dilatation. In the multivariable logistic regression analysis, age >55 years, ALP >110 U/L, and GGT >60 U/L showed statistical significance, with ORs of 1.799 (95% CI, 1.286 to 2.517), 1.590 (95% CI, 1.059 to 2.190), and 4.025 (95% CI, 2.581 to 5.550) respectively. Other variables, such as AST, ALT, and total bilirubin >4 mg/dL with CBD dilatation, were not statistically significant, with p-values of 0.921, 0.145, and 0.074, respectively.

Table 3. Odds Ratio of Predictor for Choledocholithiasis Based on ASGE Guideline Predictors

Clinical predictorUnivariable analysisMultivariable analysis
Odds ratio (95% CI)p-valueOdds ratio (95% CI)p-value
Age >55 yr1.731 (1.272–2.357)<0.0011.799 (1.286–2.517)0.001
ALP >110 U/L4.041 (3.033–5.384)<0.0011.590 (1.059–2.190)0.023
AST >45 U/L2.768 (2.082–3.680)<0.0010.981 (0.668–1.441)0.921
ALT >35 U/L3.140 (2.383–4.139)<0.0011.318 (0.904–1.981)0.145
GGT >60 U/L5.679 (4.208–7.663)<0.0014.025 (2.581–5.550)<0.001
TB >4 + CBD dilatation5.738 (2.573–12.794)<0.0011.985 (0.930–4.960)0.074

ASGE, American Society for Gastrointestinal Endoscopy; CI, confidence interval; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct.



2) According to the Korean cutoff value

The Korean cutoff values that have achieved maximum sensitivity and specificity are as follows: age >70 years, ALP >77.5 U/L, AST >28.5 U/L, ALT >26.5 U/L, GGT >82.5 U/L, and total bilirubin >0.95 mg/dL. Compared with the existing ASGE guideline, we opted to distinguish between total bilirubin and CBD dilatation rather than considering them together because combining them may miss some patients with CBD stones who only present with one of these indicators (Table 4). The number of patients aged over 70 years was 505 (41.3% of total), which is less than the 830 patients aged over 55 years (67.9%). However, the percentage of patients with CBD stones was higher in the over 70 years old group, with 158 (31.3%), compared to 212 patients (25.5%) in the over 55 years old group.

Table 4. Comparison between the 2019 ASGE Guidelines and Korean Cutoff Values

2019 ASGEKorean
Cutoff valuesNo. (%)CBD stone
present, No. (%)
Cutoff valuesNo. (%)CBD stone
present, No. (%)
Age, yr>55830 (67.9)212 (25.5)>70 505 (41.3)158 (31.3)
ALP, U/L>110309 (25.3)133 (43.0)>77.5 584 (47.8)210 (36.0)
AST, U/L>45318 (26.0)118 (37.1)>28.5 524 (42.8)178 (34.0)
ALT, U/L>35463 (37.9)164 (35.4)>26.5 504 (41.2)175 (34.7)
GGT, U/L>60516 (42.2)204 (39.5)>82.5 463 (37.9)192 (41.5)
TB, mg/dL +CBD dilatationTB >4 +CBD dilatation26 (2.1)16 (61.5)---
TB, mg/dL--->0.95 477 (39.0)176 (36.9)
CBD dilatation---Present171 (14)138 (49.8)

ASGE, American Society for Gastrointestinal Endoscopy; CBD, common bile duct; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin.



The AUC values for predictors such as age, ALP, AST, ALT, GGT, and total bilirubin were 0.609, 0.722, 0.664, 0.657, 0.740, and 0.700, respectively. As shown in Table 5, The sensitivity, specificity, PPV, and NPV were 57.0%, 63.3%, 31.3%, and 83.4% for age >70 years; 75.8%, 60.5%, 36.0%, and 89.5% for ALP >77.5 U/L; 64.3%, 63.4%, 34.0%, and 85.8% for AST >28.5 U/L; 63.2%, 65.2%, 34.7%, and 85.8% for ALT >26.5 U/L; 69.3%, 71.4%, 41.5%, and 88.8% for GGT >82.5 U/L; 63.5%, 68.2%, 36.9%, and 86.5% for total bilirubin >0.95 mg/dL; and 49.8%, 96.5%, 80.7%, and 86.8% for the presence of CBD dilatation, respectively.

Table 5. Effectiveness of Predictors for Choledocholithiasis Based on Korean Cutoff Value

Clinical predictorSensitivity,%Specificity,%Predictive value, %p-value
PositiveNegative
Age >70 yr57.063.331.383.4<0.001
ALP >77.5 U/L75.860.536.089.5<0.001
AST >28.5 U/L64.363.434.085.8<0.001
ALT >26.5 U/L63.265.234.785.8<0.001
GGT >82.5 U/L69.371.441.588.8<0.001
TB >0.95 mg/dL63.568.236.986.5<0.001
CBD dilatation49.896.580.786.8<0.001

ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct.



3. Scoring model development and model performance

Table 6 presents the univariable and multivariable analyses. The incidence rate of CBD stones in relation to each predictor was determined through the univariable analysis, which indicated that all CBD stone predictors assessed in this study are significant risk factors for the incidence rate of CBD stones. In the multivariable analysis, the presence of CBD stones was significantly associated with age >70 years (OR, 2.117; 95% CI, 1.475 to 2.705), ALP >77.5 U/L (OR, 2.405; 95% CI, 1.386 to 2.964), GGT >82.5 U/L (OR, 2.604; 95% CI, 1.910 to 4.308), and CBD dilatation (OR, 24.359; 95% CI, 15.247 to 39.918). However, other predictors such as AST >28.5 U/L, ALT >26.5 U/L, and total bilirubin >0.95 mg/dL were not significant, considering that they had a p-value >0.05. Thus, we excluded ALT, AST, and total bilirubin in the score model. As shown in Table 7, the predictors included in the construction of the scoring model are age >70 years, ALP >77.5 U/L, GGT >82.5 U/L, and CBD dilatation. The adjusted score was calculated using the beta coefficient; ultimately, the total score ranges from 0 points to 7.8 points.

Table 6. Odds Ratio of Predictor for Choledocholithiasis Based on Korean Cutoff Value

Clinical predictorUnivariable analysisMultivariable analysis
Odds ratio (95% CI)p-valueOdds ratio (95% CI)p-value
Age >70 yr2.292 (1.746–3.009)<0.0012.117 (1.475–2.705)<0.001
ALP >77.5 U/L4.794 (3.536–6.499)<0.0012.405 (1.386–2.964)<0.001
AST >28.5 U/L3.118 (2.359–4.122)<0.0010.726 (0.639–1.445)0.198
ALT >26.5 U/L3.218 (2.436–4.251)<0.0011.337 (0.870–2.011)0.250
GGT >82.5 U/L5.626 (4.203–7.532)<0.0012.604 (1.910–4.308)<0.001
TB >0.95 mg/dL3.734 (2.821–4.942)<0.0011.415 (2.101–4.382)0.085
CBD dilatation27.468 (18.054–41.789)<0.00124.359 (15.247–39.918)<0.001

CI, confidence interval; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct.



Table 7. Modeling with Clinical Predictor Odds Ratio, β Coefficients, and Adjusted Scores with Korean Cutoff Value

PredictorOdds ratio (95% CI)p-valueβAdjusted score
Intercept–3.263
Age >70 yr2.119 (1.500–2.994)<0.0010.7511.0
GGT >82.5 U/L2.962 (1.969–4.456)<0.0011.0861.4
ALP >77.5 U/L2.470 (1.600–3.812)<0.0010.9041.2
CBD dilatation24.850 (15.657–39.440)<0.0013.2134.2

CI, confidence interval; GGT, gamma-glutamyl transferase; ALP, alkaline phosphatase; CBD, common bile duct.



According to the 2019 ASGE guideline, risk groups are divided into the following according to the probability of CBD stones: low-risk group (<10%), intermediate-risk group (10%–50%), and high-risk group (>50%).5 When compared with the 2010 ASGE guideline, the 2019 ASGE guideline increased the specificity from 55% to 80% and the PPV from 79% to 83%. The rate of diagnostic ERCP decreased from 21% to 17.4%.16 Furthermore, given that the diagnostic efficacy of EUS and MRCP improves and the incidence of adverse events diminishes, the current guidelines are progressively advocating for an increase in the proportion of intermediate-risk stratifications.17

To define the risk group classification, we applied an alternative approach that entailed dividing the data into segments, each representing a 10% increase in the model-predicted likelihood of CBD stones (Supplementary Table 1). Low probability was classified as less than 10%, consistent with previous literature; intermediate probability ranged from 10% to 90%; and high probability was demarcated as any value exceeding 90%.

Table 8 presents the score range for risk stratification, as well as the sensitivity, specificity, PPV, and NPV. According to the newly developed Korean risk stratification, the score for the low-risk group is below 1.0 point, accounting for 343 patients (28.1% of the total). Among these patients, 14 (4.1%) had CBD stones, whereas 329 (95.9%) had no CBD stones. This low-risk group had sensitivity, specificity, likelihood ratio (LHR)+, and LHR− values of 94.9%, 34.8%, 1.46, and 0.15, respectively. For the intermediate-risk group, the score range is 1.0 to 5.5 points, representing 755 patients (61.7% of the total). Among them, 149 (19.7%) had CBD stones, whereas 606 (80.3%) did not. The sensitivity, specificity, LHR+, and LHR− for this group were 53.8%, 35.9%, 0.84, and 1.79, respectively. In the high-risk group, the score is ≥5.5 points. This group had 125 patients (10.2%), with 114 (91.2%) having CBD stones and 11 (8.8%) having no CBD stones. The sensitivity, specificity, LHR+, and LHR− for this group were 41.2%, 98.8%, 34.33, and 0.60, respectively.

Table 8. Assessing the Utility of Korean Criteria Risk Stratification

RiskScorePrevalence, No. (%)CBD stone, No. (%)p-valueSensitivity, %Specificity, %LHR+LHR–
Present (n=277)Absent (n=946)
Low<1.0343 (28.1)14 (4.1)329 (95.9)<0.00194.934.81.460.15
Intermediate1.0–5.5755 (61.7)149 (19.7)606 (80.7)<0.00153.835.90.841.79
High>5.5125 (10.2)114 (91.2)11 (8.8)<0.00141.298.834.330.60

CBD, common bile duct; LHR+, likelihood ratio positive; LHR–, likelihood ratio negative.



When we referred to the ASGE guidelines, the low-risk group had 188 (15.4%) patients, with CBD stones found in only two patients (1.1%) (Table 9). The sensitivity, specificity, LHR+, and LHR− in this case are 99.3%, 19.7%, 1.24, and 0.04, respectively. The intermediate-risk group consisted of 905 patients (74.0%), with 155 (17.1%) having CBD stones and 750 (82.9%) not having CBD stones. The sensitivity, specificity, LHR+, and LHR− for this group were 56.0%, 20.7%, 0.71, and 3.83, respectively. Lastly, the high-risk group consisted of 130 patients (10.6%). Among them, 120 (92.3%) had CBD stones, whereas 10 (7.7%) had no CBD stones. The sensitivity, specificity, LHR+, and LHR− for this group were 43.3%, 98.9%, 39.36, and 0.57, respectively. The validity of the Korean risk stratification was evaluated by comparing the AUC with the ASGE criteria. The AUC for the Korean risk stratification was 0.777 (95% CI, 0.75 to 0.81), whereas that for the ASGE criteria was 0.763 (95% CI, 0.73 to 0.79).

Table 9. Assessing the Utility of ASGE Criteria Risk Stratification

RiskPrevalence, No. (%)CBD stone, No. (%)p-valueSensitivity, %Specificity, %LHR+LHR–
Present (n=277)Absent (n=946)
Low188 (15.4)2 (1.1)186 (98.9)<0.00199.319.71.240.04
Intermediate905 (74.0)155 (17.1)750 (82.9)<0.00156.020.70.713.83
High130 (10.6)120 (92.3)10 (7.7)<0.00143.398.939.360.57

ASGE, American society for Gastrointestinal Endoscopy; CBD, common bile duct; LHR+, likelihood ratio positive; LHR–, likelihood ratio negative.


With the widespread practice of ERCP procedures in Korea, there is a trend towards preoperative evaluation of choledocholithiasis instead of opting for intraoperative cholangiography or transcystic CBD stone removal during surgery.18 However, due to the risk of several complications associated with ERCP, the 2019 ASGE guideline aimed to reduce the number of ERCP procedures by increasing the use of safer diagnostic methods such as EUS and MRCP.19 Evaluating the optimal strategy for patients suspected of having CBD stones requires a comprehensive assessment. Factors such as the cost, potential risks, and accessibility of diagnostic methods must also be considered.20

The pathogenesis of gallstones in the East differs from that in the West. In the East, most of the gallstones are composed of bilirubin, whereas in the West, they mostly consisted of cholesterol.21,22 Furthermore, large population studies investigating on the usefulness of the ASGE guideline in the East, especially Asians, are still limited. Our study investigated whether the 2019 ASGE guideline predictors are suitable among Korean patients. In addition, we obtained Korean cutoff values for predictors using the receiver operating characteristic curve and made a threshold-based model. Our study results suggested that the Korean cutoff values are more helpful in predicting CBD stones than the predictor cutoff values of the ASGE guideline, considering the comprehensive evaluation of factors such as sensitivity, specificity, PPV, NPV, and OR.

Consistent with existing literature, the incidence of CBD stones increased with age, showing the prevalence rates of 20% over individuals over 40 years and 30% in those over 70 years.23 The “Intermediate probability” tier of the ASGE criteria includes age >55 years as a predictive factor. As society continues to age, we need to review and adjust the cutoff values for age. Therefore, our results suggest that age >70 years is more suitable for our conditions. With the Korean criteria, the low-risk group increased from 15% to 28%, specificity improved from 19.7% to 34.8%, LHR+ improved from 1.24 to 1.46, and LHR− improved from 0.04 to 0.15. However, the sensitivity level decreased from 99.3% to 94.9%. In South Korea, MRCP is expensive and can be difficult for patients who cannot hold their breath.24 EUS also requires patient cooperation. Given that the number of people in the intermediate-risk group declined and those in the low-risk group increased, we could see the less frequent use of MRCP, EUS, and ERCP, potentially allowing for surgery without extra tests. In terms of sensitivity, specificity, and LHR+, the intermediate-risk group was better than the ASGE guideline, whereas the high-risk group showed worse.

The AUC for risk stratification in the Korean criteria was 0.777 (95% CI, 0.75 to 0.81), which was higher than the AUC for risk probability in the ASGE criteria (0.763, 95% CI, 0.73 to 0.79), indicating that the Korean criteria perform better.

Our study has some limitations. First, our study was a single-center retrospective study. Therefore, various potential biases could arise, making the achievement of optimal data aggregation challenging. Second, this study, which validated a threshold-based model through the investigation of demographic characteristics, blood tests, and imaging studies, did not consider clinical factors such as cholangitis, pancreatitis, and jaundice. Future prospective studies are needed to conceptualize predictive factors that include clinical factors. Third, our study did not consider patients in whom stones were found on intraoperative cholangiography as opposed to EUS, MRCP, or ERCP.

In conclusion, Both the ASGE and European Society of Gastrointestinal Endoscopy guidelines recommend risk stratification when evaluating CBD stones before cholecystectomy and propose respective treatment strategies. However, these guidelines are based on studies conducted in the West. Hence, we need to examine whether the results observed in the West are the same as those in Asia and to consider potential modifications to the diagnostic criteria and treatment strategies accordingly. In our study, we evaluated the utility of the cutoff values and risk stratification recommended by the ASGE guidelines. Furthermore, we developed a threshold-based model using Korean cutoff values to help future therapeutic strategies. In the future, the predictors of CBD stones in Asia should be identified in detail through more extensive cohort studies, and appropriate guidelines must be established.

No potential conflict of interest relevant to this article was reported.

Study concept and design: K.R., J.H.W. Data acquisition: K.R. Data analysis and interpretation: J.H.W., H.C. Drafting of the manuscript: J.H.W. Critical revision of the manuscript for important intellectual content: all authors. Investigation: K.R., J.H.W., H.C. Methodology: K.R., J.H.W., H.C. Validation: K.R. Visualization: J.H.W., H.C. Approval of final manuscript: all authors.

  1. Gallaher JR, Charles A. Acute cholecystitis: a review. JAMA 2022;327:965-975.
    Pubmed CrossRef
  2. Ukegjini K, Schmied BM. Diagnosis and treatment of acute cholecystitis. Ther Umsch 2020;77:133-146.
    Pubmed CrossRef
  3. Zong Y, Stanger BZ. Molecular mechanisms of bile duct development. Int J Biochem Cell Biol 2011;43:257-264.
    Pubmed KoreaMed CrossRef
  4. Freitas ML, Bell RL, Duffy AJ. Choledocholithiasis: evolving standards for diagnosis and management. World J Gastroenterol 2006;12:3162-3167.
    Pubmed KoreaMed CrossRef
  5. Buxbaum JL, Abbas Fehmi SM, et al; ASGE Standards of Practice Committee. ASGE guideline on the role of endoscopy in the evaluation and management of choledocholithiasis. Gastrointest Endosc 2019;89:1075-1105.
    Pubmed KoreaMed CrossRef
  6. Portincasa P, Di Ciaula A, de Bari O, Garruti G, Palmieri VO, Wang DQ. Management of gallstones and its related complications. Expert Rev Gastroenterol Hepatol 2016;10:93-112.
    Pubmed CrossRef
  7. Depew WT. Endoscopic retrograde cholangiopancreatography. Can Med Assoc J 1981;125:531-533.
    Pubmed KoreaMed CrossRef
  8. Tanaka M, Ikeda S, Nakayama F. Change in bile duct pressure responses after cholecystectomy: loss of gallbladder as a pressure reservoir. Gastroenterology 1984;87:1154-1159.
    Pubmed CrossRef
  9. Kedia P, Tarnasky PR. Endoscopic management of complex biliary stone disease. Gastrointest Endosc Clin N Am 2019;29:257-275.
    Pubmed CrossRef
  10. Rácz I, Rejchrt S, Hassan M. Complications of ERCP: ethical obligations and legal consequences. Dig Dis 2008;26:49-55.
    Pubmed CrossRef
  11. Afzalpurkar S, Giri S, Kasturi S, Ingawale S, Sundaram S. Magnetic resonance cholangiopancreatography versus endoscopic ultrasound for diagnosis of choledocholithiasis: an updated systematic review and meta-analysis. Surg Endosc 2023;37:2566-2573.
    Pubmed CrossRef
  12. Toro-Calle J, Guzmán-Arango C, Ramírez-Ceballos M, Guzmán-Arango N. Are the ASGE criteria sufficient to stratify the risk of choledocholithiasis?. Rev Colomb Gastroenterol 2020;35:304-310.
    CrossRef
  13. He H, Tan C, Wu J, et al. Accuracy of ASGE high-risk criteria in evaluation of patients with suspected common bile duct stones. Gastrointest Endosc 2017;86:525-532.
    Pubmed CrossRef
  14. Yang MH, Chen TH, Wang SE, et al. Biochemical predictors for absence of common bile duct stones in patients undergoing laparoscopic cholecystectomy. Surg Endosc 2008;22:1620-1624.
    Pubmed CrossRef
  15. Carriere V, Conway J, Evans J, Shokoohi S, Mishra G. Which patients with dilated common bile and/or pancreatic ducts have positive findings on EUS?. J Interv Gastroenterol 2012;2:168-171.
    Pubmed KoreaMed CrossRef
  16. Lee YN, Moon JH. Optimal predictive criteria for common bile duct stones: the search continues. Clin Endosc 2021;54:147-148.
    Pubmed KoreaMed CrossRef
  17. Tse F, Liu L, Barkun AN, Armstrong D, Moayyedi P. EUS: a meta-analysis of test performance in suspected choledocholithiasis. Gastrointest Endosc 2008;67:235-244.
    Pubmed CrossRef
  18. Ragulin-Coyne E, Witkowski ER, Chau Z, et al. Is routine intraoperative cholangiogram necessary in the twenty-first century? A national view. J Gastrointest Surg 2013;17:434-442.
    Pubmed KoreaMed CrossRef
  19. Jacob JS, Lee ME, Chew EY, Thrift AP, Sealock RJ. Evaluating the revised American Society for Gastrointestinal Endoscopy Guidelines for common bile duct stone diagnosis. Clin Endosc 2021;54:269-274.
    Pubmed KoreaMed CrossRef
  20. Mark DH, Flamm CR, Aronson N. Evidence-based assessment of diagnostic modalities for common bile duct stones. Gastrointest Endosc 2002;56(6 Suppl):S190-S194.
    Pubmed CrossRef
  21. Tazuma S. Gallstone disease: epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic). Best Pract Res Clin Gastroenterol 2006;20:1075-1083.
    Pubmed CrossRef
  22. Stinton LM, Myers RP, Shaffer EA. Epidemiology of gallstones. Gastroenterol Clin North Am 2010;39:157-169.
    Pubmed CrossRef
  23. Hu KC, Chu CH, Wang HY, et al. How does aging affect presentation and management of biliary stones?. J Am Geriatr Soc 2016;64:2330-2335.
    Pubmed CrossRef
  24. Vacca G, Reginelli A, Urraro F, et al. Magnetic resonance severity index assessed by T1-weighted imaging for acute pancreatitis: correlation with clinical outcomes and grading of the revised Atlanta classification-a narrative review. Gland Surg 2020;9:2312-2320.
    Pubmed KoreaMed CrossRef

Article

ahead

Gut and Liver

Published online May 7, 2024

Copyright © Gut and Liver.

Predictors of Choledocholithiasis in Cholecystectomy Patients and Their Cutoff Values and Prediction Model in Korea in Comparison with the 2019 ASGE Guidelines

Jung Hun Woo1 , Hwanhyi Cho1 , Kihyun Ryu1 , Young Woo Choi1 , Sanghyuk Lee1 , Tae Hee Lee1 , Dae Sung Kim1 , In Seok Choi2 , Ju Ik Moon2 , Seung Jae Lee2

Departments of 1Gastroenterology and 2General Surgery, Konyang University Myunggok Medical Research Institute, Daejeon, Korea

Correspondence to:Kihyun Ryu
ORCID https://orcid.org/0000-0003-0595-6776
E-mail medidrug@kyuh.ac.kr

Jung Hun Woo and Hwanhyi Cho contributed equally to this work as first authors.

Received: December 20, 2023; Revised: February 9, 2024; Accepted: February 13, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims: In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) established clinical predictors for choledocholithiasis. Our study was designed to evaluate these predictors within the Korean clinical context, establish cutoff values, and develop a predictive model.
Methods: This retrospective study analyzed patients who underwent laparoscopic cholecystectomy. The relationships between choledocholithiasis and predictors including age, blood tests, and imaging findings were assessed through univariate and multivariate logistic regression analyses. We established Korean cutoff values for these predictors and developed a scoring system for choledocholithiasis using a multivariate logistic regression. The performance of this scoring system was then compared with that of the 2019 ASGE guidelines through a receiver operating characteristic curve.
Results: We established Korean cutoff values for age (>70 years), alanine aminotransferase (>26.5 U/L), aspartate aminotransferase (>28.5 U/L), gamma-glutamyl transferase (GGT; >82.5 U/L), alkaline phosphatase (ALP; >77.5 U/L), and total bilirubin (>0.95 mg/dL). In the multivariate analysis, only age >70 years, GGT >77.5 U/L, ALP >77.5 U/L, and common bile duct dilatation remained significant. We then developed a new Korean risk stratification model from the multivariate analysis, with an area under the curve of 0.777 (95% confidence interval, 0.75 to 0.81). Our model was stratified into the low-risk, intermediate-risk, and high-risk groups with the scores being <1.0, 1.0–5.5, and >5.5, respectively.
Conclusions: Predictors of choledocholithiasis in cholecystectomy patients and their cutoff values in Korean should be adjusted and further studies are needed to develop appropriate guidelines.

Keywords: Choledocholithiasis, Cholecystectomy, Preoperative period

INTRODUCTION

Cholecystitis refers to inflammation of the gallbladder that range from mild symptoms, such as abdominal pain, nausea, and vomiting, to severe conditions like septic shock or gallbladder perforation. The treatment of choice for this condition is cholecystectomy.1,2 Choledocholithiasis refers to the presence of gallstones in the bile duct system, the common bile duct (CBD) and the common hepatic duct, both of which are integral components of a shared pathway facilitating bile flow from the liver to the duodenum.3 Choledocholithiasis is found in 10% to 20% of patients with cholecystitis or symptomatic cholelithiasis, commonly occurs as a result of the movement of gallstones from the gallbladder.4,5 Predicting CBD stones before cholecystectomy is important in the prognosis of patients with cholecystitis.6 For several decades, endoscopic retrograde cholangiopancreatography (ERCP) was considered the gold standard for diagnosing CBD stones.7 When the gallbladder is removed, the storage space for bile is decreased, leading to increased pressure within the bile ducts. This can cause bile duct stones to move to the distal part and become impacted at the sphincter, resulting in pancreatitis or cholangitis. Prophylactic removal of these stones prior to surgery can prevent the occurrence of such adverse events.8 However, up to 6%–15% of patients undergoing ERCP are at risk for several complications, such as post-ERCP pancreatitis, duodenal perforation, and hemorrhage.9 Therefore, ERCP should be conducted for therapeutic purposes.10 In the 1990s, both endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP), which are low-risk diagnostic modalities, were introduced as alternative diagnostic modalities to ERCP for detecting CBD stones.11

In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) revised its clinical guidelines for diagnosing and managing patients with calculous cholecystitis or symptomatic cholelithiasis, using clinical predictors to identify risk groups for choledocholithiasis. These predictors include imaging study findings (e.g., the presence of CBD stones on ultrasonography), abnormal laboratory results (e.g., abnormal liver function tests or elevated total bilirubin levels of 4 mg/dL), and clinical symptoms (e.g., abdominal pain, fever, and jaundice).5 Recently, various studies had been conducted on whether the predictors presented in the ASGE guidelines are effective, and some studies argued that these predictors need adjustment.12

In Korea, few studies examined the clinical utility of the predictors recommended by the ASGE guidelines. Many centers often do not screen for preoperative choledocholithiasis in candidates according to ASGE guidelines, and cases are frequently identified passively after cholecystectomy due to increased biliary pressure causing cholangitis or pancreatitis. This study, conducted at a single center, screened all patients undergoing cholecystectomy for benign cholecystitis, assessing the suspicion of choledocholithiasis through preoperative evaluation, subsequently determining the necessity for ERCP based on these assessments. Our study aimed to evaluate the performance of ASGE’s clinical predictors within a Korean clinical context. We also sought to establish a cutoff value for these predictors and subsequently build a predictive model tailored to the Korean patient population, enhancing its clinical applicability and usefulness in everyday practice.

MATERIALS AND METHODS

1. Study design

We conducted a single-center retrospective study at Konyang University Hospital in South Korea. This study received approval from the Institutional Review Board of Konyang University Medical Center (IRB number: 2022-10-002-007) and conformed to the principles of the Declaration of Helsinki and Good Clinical Practice. The informed consent was waived.

Patients who underwent laparoscopic cholecystectomy between January 2009 and March 2021 were included. Patient data such as age, sex, and five blood test types (alkaline phosphatase [ALP], aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transferase [GGT], and total bilirubin) were obtained from the medical records. We screened the majority of patients with acute cholecystitis planned for cholecystectomy using EUS or MRCP, in whom choledocholithiasis was not clearly observed on computed tomography or abdominal ultrasonography. Conversely, we excluded patients with liver cirrhosis, viral hepatitis, chronic alcoholism, biliary malignancy, and previous biliary tract intervention such as surgery or ERCP.

2. Predictors and outcomes

Factors associated with CBD stone predictors have been determined according to the 2019 ASGE guidelines for predictor identification. Predictive factors are divided into three main areas: age, blood test results, and imaging findings. The age is classified with a cutoff point at 55 years. For blood tests, particularly liver enzyme levels, exceeding the values of 110 U/L for ALP, 35 U/L for AST, 45 U/L for ALT,13 60 U/L for GGT, and 4.0 mg/dL for total bilirubin is considered abnormal.14 Regarding imaging, CT or ultrasound is used to assess whether CBD dilatation and CBD stones are present or absent. CBD dilatation refers to CBD size more than 6 mm.15 The primary outcome was the presence of a CBD stone, which is confirmed via procedures such as ERCP, MRCP, EUS, or surgery.

3. Statistical analysis

A univariate logistic regression analysis was conducted to calculate the odds ratio (OR) between predictors and presence of CBD stones, with 95% confidence intervals. Multivariable logistic regression analysis, assessing the impact of predictors on CBD stones in the presence of other risk factors, was the main statistical method for our Korean score model. Predictors were chosen using a backward stepwise method. The Korean threshold for CBD stone predictors, including age and liver enzyme levels, was established by receiver operating characteristic curve analysis. The threshold was set at the point where sensitivity and specificity were maximized. Continuous variables were analyzed using the Student t-test or Mann-Whitney U test, as appropriate. Categorial variables, such as sex and risk groups, were compared using the Pearson chi-square test or Fisher exact test. All statistical data were analyzed using the SPSS software (version 25.0; IBM Corp., Armonk, NY, USA), and p-values <0.05 were considered statistically significant.

4. Scoring system development and verification

The effectiveness of Korean cutoff values was evaluated by calculating the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and OR.

Based on these Korean cutoff values, a threshold-based model was constructed using a multivariable logistic regression. Significant predictors that contribute to the scoring system were selected through a backward stepwise method. We assigned scores according to the presence of these predictors using their logit coefficient values. The total score was distributed into 10% segments, from which we designated three risk groups: the high-risk group (cutoff score >90%), intermediate-risk group (cutoff score 10%–90%), and low-risk group (cutoff score <10%). The effectiveness of the Korean threshold-based model was evaluated by sensitivity, specificity, likelihood ratio positive, and likelihood ratio negative.

The performance of our model was evaluated using the area under the receiver operating characteristic curve (AUC). Following the TRIPOD statement’s suggestion for model comparisons, we compared our proposed model with an existing guideline. Considering that CBD stone scoring models deemed acceptable in our context are still unestablished, we selected the widely adopted 2019 version of the ASGE guideline, to be compared with our model.

RESULTS

1. Baseline characteristics

Among the 1,850 patients who underwent laparoscopic cholecystectomy for calculous cholecystitis or symptomatic cholelithiasis, 1,223 were included in the study after excluding those with incomplete medical records and those who met the exclusion criteria (n=627). Of these included patients, 277 were diagnosed with CBD stones, whereas 946 patients had no CBD stones (Fig. 1).

Figure 1. Study population flow diagram.

Table 1 shows patients’ baseline characteristics. The mean age was slightly higher in those with CBD stones than in those without CBD stones (68.52 years vs 62.50 years). The percentages of patients aged ≥55 years old were higher in the CBD stone group than in the group without CBD stones (76.5% vs 65.3%). The median results of the liver function test–ALP, AST, ALT, and GGT–in the CBD stone group were 106.0, 37.0, 41.0, and 224.0 U/L, whereas those in the group without CBD stones were 69.0, 23.5, 17.0, and 32.0 U/L, respectively. Regarding the total bilirubin levels, the former group had 1.18 mg/dL, whereas the latter group had 0.72 mg/dL.

Table 1 . Distribution of Variables between Groups According to CBD Stone Status.

VariableCBD stonep-value
Present (n=277)Absent (n=946)
Age, yr68.52±16.6062.50±16.88<0.001
Age >55 yr212 (76.5)618 (65.3)<0.001
Male sex168 (60.6)421 (44.5)<0.001
Liver function test
ALP, U/L106.0 (78.0–169.0)69.0 (55.0–97.0)
AST, U/L37.0 (24.0–82.0)23.5 (18.0–39.0)
ALT, U/L41.0 (16.0–163.0)17.0 (12.0–42.0)
Total bilirubin, mg/dL1.18 (0.72–1.80)0.72 (0.51–1.08)
GGT, U/L224 (56.0–451.5)32.0 (17.0–109.0)
CBD dilatation138 (49.8)33 (3.4)<0.001
Risk<0.001
High risk120 (43.3)10 (1.0)
Intermediate risk155 (56.0)750 (79.3)
Low risk2 (0.7)186 (19.7)
Diagnostic method0.125
MRCP164 (59.2)623 (65.9)
EUS16 (5.8)44 (4.7)
Preoperative ERCP264 (95.3)0

Data are presented as mean±SD, number (%), or median (interquartile range)..

CBD, common bile duct; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; MRCP, magnetic resonance cholangiopancreatography; EUS, endoscopic ultrasonography; ERCP, endoscopic retrograde cholangiopancreatography..



2. Utility of CBD stone predictors

The sensitivity, specificity, PPV, NPV, and OR for CBD stone predictors were obtained according to the 2019 ASGE guideline and the Korean cutoff value.

1) According to 2019 ASGE guidelines

As shown in Table 2, the sensitivity, specificity, PPV, and NPV were 76.5%, 34.7%, 25.5%, and 83.5% for age >55 years; 59.2%, 68.4%, 35.4%, and 85.1% for ALT >35 U/L; and 5.8%, 98.9%, 61.5%, and 78.2% for total bilirubin >4 mg/dL and CBD dilatation, respectively.

Table 2 . Effectiveness of Predictors for Choledocholithiasis Based on ASGE Guidelines.

PredictorSensitivity, %Specificity, %Predictive value, %p-value
PositiveNegative
Age >55 yr76.534.725.583.5<0.001
ALP >110 U/L48.081.443.084.2<0.001
AST >45 U/L42.678.937.182.4<0.001
ALT >35 U/L59.268.435.485.1<0.001
GGT >60 U/L73.667.039.589.7<0.001
TB >4 + CBD dilatation5.898.961.578.2<0.001

ASGE, American Society for Gastrointestinal Endoscopy; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct..



In the univariable logistic regression analysis, Table 3 shows that the OR was 1.731 (95% confidence interval [CI], 1.272 to 2.357) for age >55 years, 4.041 (95% CI, 3.033 to 5.384) for ALP >110 U/L, 2.768 (95% CI, 2.082 to 3.680) for AST >45 U/L, 3.140 (95% CI, 2.383 to 4.139) for ALT >35 U/L, 5.679 (95% CI, 4.208 to 7.663) for GGT >60 U/L, and 5.738 (95% CI, 2.573 to 12.794) for total bilirubin >4 mg/dL with CBD dilatation. In the multivariable logistic regression analysis, age >55 years, ALP >110 U/L, and GGT >60 U/L showed statistical significance, with ORs of 1.799 (95% CI, 1.286 to 2.517), 1.590 (95% CI, 1.059 to 2.190), and 4.025 (95% CI, 2.581 to 5.550) respectively. Other variables, such as AST, ALT, and total bilirubin >4 mg/dL with CBD dilatation, were not statistically significant, with p-values of 0.921, 0.145, and 0.074, respectively.

Table 3 . Odds Ratio of Predictor for Choledocholithiasis Based on ASGE Guideline Predictors.

Clinical predictorUnivariable analysisMultivariable analysis
Odds ratio (95% CI)p-valueOdds ratio (95% CI)p-value
Age >55 yr1.731 (1.272–2.357)<0.0011.799 (1.286–2.517)0.001
ALP >110 U/L4.041 (3.033–5.384)<0.0011.590 (1.059–2.190)0.023
AST >45 U/L2.768 (2.082–3.680)<0.0010.981 (0.668–1.441)0.921
ALT >35 U/L3.140 (2.383–4.139)<0.0011.318 (0.904–1.981)0.145
GGT >60 U/L5.679 (4.208–7.663)<0.0014.025 (2.581–5.550)<0.001
TB >4 + CBD dilatation5.738 (2.573–12.794)<0.0011.985 (0.930–4.960)0.074

ASGE, American Society for Gastrointestinal Endoscopy; CI, confidence interval; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct..



2) According to the Korean cutoff value

The Korean cutoff values that have achieved maximum sensitivity and specificity are as follows: age >70 years, ALP >77.5 U/L, AST >28.5 U/L, ALT >26.5 U/L, GGT >82.5 U/L, and total bilirubin >0.95 mg/dL. Compared with the existing ASGE guideline, we opted to distinguish between total bilirubin and CBD dilatation rather than considering them together because combining them may miss some patients with CBD stones who only present with one of these indicators (Table 4). The number of patients aged over 70 years was 505 (41.3% of total), which is less than the 830 patients aged over 55 years (67.9%). However, the percentage of patients with CBD stones was higher in the over 70 years old group, with 158 (31.3%), compared to 212 patients (25.5%) in the over 55 years old group.

Table 4 . Comparison between the 2019 ASGE Guidelines and Korean Cutoff Values.

2019 ASGEKorean
Cutoff valuesNo. (%)CBD stone
present, No. (%)
Cutoff valuesNo. (%)CBD stone
present, No. (%)
Age, yr>55830 (67.9)212 (25.5)>70 505 (41.3)158 (31.3)
ALP, U/L>110309 (25.3)133 (43.0)>77.5 584 (47.8)210 (36.0)
AST, U/L>45318 (26.0)118 (37.1)>28.5 524 (42.8)178 (34.0)
ALT, U/L>35463 (37.9)164 (35.4)>26.5 504 (41.2)175 (34.7)
GGT, U/L>60516 (42.2)204 (39.5)>82.5 463 (37.9)192 (41.5)
TB, mg/dL +CBD dilatationTB >4 +CBD dilatation26 (2.1)16 (61.5)---
TB, mg/dL--->0.95 477 (39.0)176 (36.9)
CBD dilatation---Present171 (14)138 (49.8)

ASGE, American Society for Gastrointestinal Endoscopy; CBD, common bile duct; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin..



The AUC values for predictors such as age, ALP, AST, ALT, GGT, and total bilirubin were 0.609, 0.722, 0.664, 0.657, 0.740, and 0.700, respectively. As shown in Table 5, The sensitivity, specificity, PPV, and NPV were 57.0%, 63.3%, 31.3%, and 83.4% for age >70 years; 75.8%, 60.5%, 36.0%, and 89.5% for ALP >77.5 U/L; 64.3%, 63.4%, 34.0%, and 85.8% for AST >28.5 U/L; 63.2%, 65.2%, 34.7%, and 85.8% for ALT >26.5 U/L; 69.3%, 71.4%, 41.5%, and 88.8% for GGT >82.5 U/L; 63.5%, 68.2%, 36.9%, and 86.5% for total bilirubin >0.95 mg/dL; and 49.8%, 96.5%, 80.7%, and 86.8% for the presence of CBD dilatation, respectively.

Table 5 . Effectiveness of Predictors for Choledocholithiasis Based on Korean Cutoff Value.

Clinical predictorSensitivity,%Specificity,%Predictive value, %p-value
PositiveNegative
Age >70 yr57.063.331.383.4<0.001
ALP >77.5 U/L75.860.536.089.5<0.001
AST >28.5 U/L64.363.434.085.8<0.001
ALT >26.5 U/L63.265.234.785.8<0.001
GGT >82.5 U/L69.371.441.588.8<0.001
TB >0.95 mg/dL63.568.236.986.5<0.001
CBD dilatation49.896.580.786.8<0.001

ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct..



3. Scoring model development and model performance

Table 6 presents the univariable and multivariable analyses. The incidence rate of CBD stones in relation to each predictor was determined through the univariable analysis, which indicated that all CBD stone predictors assessed in this study are significant risk factors for the incidence rate of CBD stones. In the multivariable analysis, the presence of CBD stones was significantly associated with age >70 years (OR, 2.117; 95% CI, 1.475 to 2.705), ALP >77.5 U/L (OR, 2.405; 95% CI, 1.386 to 2.964), GGT >82.5 U/L (OR, 2.604; 95% CI, 1.910 to 4.308), and CBD dilatation (OR, 24.359; 95% CI, 15.247 to 39.918). However, other predictors such as AST >28.5 U/L, ALT >26.5 U/L, and total bilirubin >0.95 mg/dL were not significant, considering that they had a p-value >0.05. Thus, we excluded ALT, AST, and total bilirubin in the score model. As shown in Table 7, the predictors included in the construction of the scoring model are age >70 years, ALP >77.5 U/L, GGT >82.5 U/L, and CBD dilatation. The adjusted score was calculated using the beta coefficient; ultimately, the total score ranges from 0 points to 7.8 points.

Table 6 . Odds Ratio of Predictor for Choledocholithiasis Based on Korean Cutoff Value.

Clinical predictorUnivariable analysisMultivariable analysis
Odds ratio (95% CI)p-valueOdds ratio (95% CI)p-value
Age >70 yr2.292 (1.746–3.009)<0.0012.117 (1.475–2.705)<0.001
ALP >77.5 U/L4.794 (3.536–6.499)<0.0012.405 (1.386–2.964)<0.001
AST >28.5 U/L3.118 (2.359–4.122)<0.0010.726 (0.639–1.445)0.198
ALT >26.5 U/L3.218 (2.436–4.251)<0.0011.337 (0.870–2.011)0.250
GGT >82.5 U/L5.626 (4.203–7.532)<0.0012.604 (1.910–4.308)<0.001
TB >0.95 mg/dL3.734 (2.821–4.942)<0.0011.415 (2.101–4.382)0.085
CBD dilatation27.468 (18.054–41.789)<0.00124.359 (15.247–39.918)<0.001

CI, confidence interval; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct..



Table 7 . Modeling with Clinical Predictor Odds Ratio, β Coefficients, and Adjusted Scores with Korean Cutoff Value.

PredictorOdds ratio (95% CI)p-valueβAdjusted score
Intercept–3.263
Age >70 yr2.119 (1.500–2.994)<0.0010.7511.0
GGT >82.5 U/L2.962 (1.969–4.456)<0.0011.0861.4
ALP >77.5 U/L2.470 (1.600–3.812)<0.0010.9041.2
CBD dilatation24.850 (15.657–39.440)<0.0013.2134.2

CI, confidence interval; GGT, gamma-glutamyl transferase; ALP, alkaline phosphatase; CBD, common bile duct..



According to the 2019 ASGE guideline, risk groups are divided into the following according to the probability of CBD stones: low-risk group (<10%), intermediate-risk group (10%–50%), and high-risk group (>50%).5 When compared with the 2010 ASGE guideline, the 2019 ASGE guideline increased the specificity from 55% to 80% and the PPV from 79% to 83%. The rate of diagnostic ERCP decreased from 21% to 17.4%.16 Furthermore, given that the diagnostic efficacy of EUS and MRCP improves and the incidence of adverse events diminishes, the current guidelines are progressively advocating for an increase in the proportion of intermediate-risk stratifications.17

To define the risk group classification, we applied an alternative approach that entailed dividing the data into segments, each representing a 10% increase in the model-predicted likelihood of CBD stones (Supplementary Table 1). Low probability was classified as less than 10%, consistent with previous literature; intermediate probability ranged from 10% to 90%; and high probability was demarcated as any value exceeding 90%.

Table 8 presents the score range for risk stratification, as well as the sensitivity, specificity, PPV, and NPV. According to the newly developed Korean risk stratification, the score for the low-risk group is below 1.0 point, accounting for 343 patients (28.1% of the total). Among these patients, 14 (4.1%) had CBD stones, whereas 329 (95.9%) had no CBD stones. This low-risk group had sensitivity, specificity, likelihood ratio (LHR)+, and LHR− values of 94.9%, 34.8%, 1.46, and 0.15, respectively. For the intermediate-risk group, the score range is 1.0 to 5.5 points, representing 755 patients (61.7% of the total). Among them, 149 (19.7%) had CBD stones, whereas 606 (80.3%) did not. The sensitivity, specificity, LHR+, and LHR− for this group were 53.8%, 35.9%, 0.84, and 1.79, respectively. In the high-risk group, the score is ≥5.5 points. This group had 125 patients (10.2%), with 114 (91.2%) having CBD stones and 11 (8.8%) having no CBD stones. The sensitivity, specificity, LHR+, and LHR− for this group were 41.2%, 98.8%, 34.33, and 0.60, respectively.

Table 8 . Assessing the Utility of Korean Criteria Risk Stratification.

RiskScorePrevalence, No. (%)CBD stone, No. (%)p-valueSensitivity, %Specificity, %LHR+LHR–
Present (n=277)Absent (n=946)
Low<1.0343 (28.1)14 (4.1)329 (95.9)<0.00194.934.81.460.15
Intermediate1.0–5.5755 (61.7)149 (19.7)606 (80.7)<0.00153.835.90.841.79
High>5.5125 (10.2)114 (91.2)11 (8.8)<0.00141.298.834.330.60

CBD, common bile duct; LHR+, likelihood ratio positive; LHR–, likelihood ratio negative..



When we referred to the ASGE guidelines, the low-risk group had 188 (15.4%) patients, with CBD stones found in only two patients (1.1%) (Table 9). The sensitivity, specificity, LHR+, and LHR− in this case are 99.3%, 19.7%, 1.24, and 0.04, respectively. The intermediate-risk group consisted of 905 patients (74.0%), with 155 (17.1%) having CBD stones and 750 (82.9%) not having CBD stones. The sensitivity, specificity, LHR+, and LHR− for this group were 56.0%, 20.7%, 0.71, and 3.83, respectively. Lastly, the high-risk group consisted of 130 patients (10.6%). Among them, 120 (92.3%) had CBD stones, whereas 10 (7.7%) had no CBD stones. The sensitivity, specificity, LHR+, and LHR− for this group were 43.3%, 98.9%, 39.36, and 0.57, respectively. The validity of the Korean risk stratification was evaluated by comparing the AUC with the ASGE criteria. The AUC for the Korean risk stratification was 0.777 (95% CI, 0.75 to 0.81), whereas that for the ASGE criteria was 0.763 (95% CI, 0.73 to 0.79).

Table 9 . Assessing the Utility of ASGE Criteria Risk Stratification.

RiskPrevalence, No. (%)CBD stone, No. (%)p-valueSensitivity, %Specificity, %LHR+LHR–
Present (n=277)Absent (n=946)
Low188 (15.4)2 (1.1)186 (98.9)<0.00199.319.71.240.04
Intermediate905 (74.0)155 (17.1)750 (82.9)<0.00156.020.70.713.83
High130 (10.6)120 (92.3)10 (7.7)<0.00143.398.939.360.57

ASGE, American society for Gastrointestinal Endoscopy; CBD, common bile duct; LHR+, likelihood ratio positive; LHR–, likelihood ratio negative..


DISCUSSION

With the widespread practice of ERCP procedures in Korea, there is a trend towards preoperative evaluation of choledocholithiasis instead of opting for intraoperative cholangiography or transcystic CBD stone removal during surgery.18 However, due to the risk of several complications associated with ERCP, the 2019 ASGE guideline aimed to reduce the number of ERCP procedures by increasing the use of safer diagnostic methods such as EUS and MRCP.19 Evaluating the optimal strategy for patients suspected of having CBD stones requires a comprehensive assessment. Factors such as the cost, potential risks, and accessibility of diagnostic methods must also be considered.20

The pathogenesis of gallstones in the East differs from that in the West. In the East, most of the gallstones are composed of bilirubin, whereas in the West, they mostly consisted of cholesterol.21,22 Furthermore, large population studies investigating on the usefulness of the ASGE guideline in the East, especially Asians, are still limited. Our study investigated whether the 2019 ASGE guideline predictors are suitable among Korean patients. In addition, we obtained Korean cutoff values for predictors using the receiver operating characteristic curve and made a threshold-based model. Our study results suggested that the Korean cutoff values are more helpful in predicting CBD stones than the predictor cutoff values of the ASGE guideline, considering the comprehensive evaluation of factors such as sensitivity, specificity, PPV, NPV, and OR.

Consistent with existing literature, the incidence of CBD stones increased with age, showing the prevalence rates of 20% over individuals over 40 years and 30% in those over 70 years.23 The “Intermediate probability” tier of the ASGE criteria includes age >55 years as a predictive factor. As society continues to age, we need to review and adjust the cutoff values for age. Therefore, our results suggest that age >70 years is more suitable for our conditions. With the Korean criteria, the low-risk group increased from 15% to 28%, specificity improved from 19.7% to 34.8%, LHR+ improved from 1.24 to 1.46, and LHR− improved from 0.04 to 0.15. However, the sensitivity level decreased from 99.3% to 94.9%. In South Korea, MRCP is expensive and can be difficult for patients who cannot hold their breath.24 EUS also requires patient cooperation. Given that the number of people in the intermediate-risk group declined and those in the low-risk group increased, we could see the less frequent use of MRCP, EUS, and ERCP, potentially allowing for surgery without extra tests. In terms of sensitivity, specificity, and LHR+, the intermediate-risk group was better than the ASGE guideline, whereas the high-risk group showed worse.

The AUC for risk stratification in the Korean criteria was 0.777 (95% CI, 0.75 to 0.81), which was higher than the AUC for risk probability in the ASGE criteria (0.763, 95% CI, 0.73 to 0.79), indicating that the Korean criteria perform better.

Our study has some limitations. First, our study was a single-center retrospective study. Therefore, various potential biases could arise, making the achievement of optimal data aggregation challenging. Second, this study, which validated a threshold-based model through the investigation of demographic characteristics, blood tests, and imaging studies, did not consider clinical factors such as cholangitis, pancreatitis, and jaundice. Future prospective studies are needed to conceptualize predictive factors that include clinical factors. Third, our study did not consider patients in whom stones were found on intraoperative cholangiography as opposed to EUS, MRCP, or ERCP.

In conclusion, Both the ASGE and European Society of Gastrointestinal Endoscopy guidelines recommend risk stratification when evaluating CBD stones before cholecystectomy and propose respective treatment strategies. However, these guidelines are based on studies conducted in the West. Hence, we need to examine whether the results observed in the West are the same as those in Asia and to consider potential modifications to the diagnostic criteria and treatment strategies accordingly. In our study, we evaluated the utility of the cutoff values and risk stratification recommended by the ASGE guidelines. Furthermore, we developed a threshold-based model using Korean cutoff values to help future therapeutic strategies. In the future, the predictors of CBD stones in Asia should be identified in detail through more extensive cohort studies, and appropriate guidelines must be established.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

AUTHOR CONTRIBUTIONS

Study concept and design: K.R., J.H.W. Data acquisition: K.R. Data analysis and interpretation: J.H.W., H.C. Drafting of the manuscript: J.H.W. Critical revision of the manuscript for important intellectual content: all authors. Investigation: K.R., J.H.W., H.C. Methodology: K.R., J.H.W., H.C. Validation: K.R. Visualization: J.H.W., H.C. Approval of final manuscript: all authors.

SUPPLEMENTARY MATERIALS

Supplementary materials can be accessed at https://doi.org/10.5009/gnl230534.

Fig 1.

Figure 1.Study population flow diagram.
Gut and Liver 2024; :

Table 1 Distribution of Variables between Groups According to CBD Stone Status

VariableCBD stonep-value
Present (n=277)Absent (n=946)
Age, yr68.52±16.6062.50±16.88<0.001
Age >55 yr212 (76.5)618 (65.3)<0.001
Male sex168 (60.6)421 (44.5)<0.001
Liver function test
ALP, U/L106.0 (78.0–169.0)69.0 (55.0–97.0)
AST, U/L37.0 (24.0–82.0)23.5 (18.0–39.0)
ALT, U/L41.0 (16.0–163.0)17.0 (12.0–42.0)
Total bilirubin, mg/dL1.18 (0.72–1.80)0.72 (0.51–1.08)
GGT, U/L224 (56.0–451.5)32.0 (17.0–109.0)
CBD dilatation138 (49.8)33 (3.4)<0.001
Risk<0.001
High risk120 (43.3)10 (1.0)
Intermediate risk155 (56.0)750 (79.3)
Low risk2 (0.7)186 (19.7)
Diagnostic method0.125
MRCP164 (59.2)623 (65.9)
EUS16 (5.8)44 (4.7)
Preoperative ERCP264 (95.3)0

Data are presented as mean±SD, number (%), or median (interquartile range).

CBD, common bile duct; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; MRCP, magnetic resonance cholangiopancreatography; EUS, endoscopic ultrasonography; ERCP, endoscopic retrograde cholangiopancreatography.


Table 2 Effectiveness of Predictors for Choledocholithiasis Based on ASGE Guidelines

PredictorSensitivity, %Specificity, %Predictive value, %p-value
PositiveNegative
Age >55 yr76.534.725.583.5<0.001
ALP >110 U/L48.081.443.084.2<0.001
AST >45 U/L42.678.937.182.4<0.001
ALT >35 U/L59.268.435.485.1<0.001
GGT >60 U/L73.667.039.589.7<0.001
TB >4 + CBD dilatation5.898.961.578.2<0.001

ASGE, American Society for Gastrointestinal Endoscopy; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct.


Table 3 Odds Ratio of Predictor for Choledocholithiasis Based on ASGE Guideline Predictors

Clinical predictorUnivariable analysisMultivariable analysis
Odds ratio (95% CI)p-valueOdds ratio (95% CI)p-value
Age >55 yr1.731 (1.272–2.357)<0.0011.799 (1.286–2.517)0.001
ALP >110 U/L4.041 (3.033–5.384)<0.0011.590 (1.059–2.190)0.023
AST >45 U/L2.768 (2.082–3.680)<0.0010.981 (0.668–1.441)0.921
ALT >35 U/L3.140 (2.383–4.139)<0.0011.318 (0.904–1.981)0.145
GGT >60 U/L5.679 (4.208–7.663)<0.0014.025 (2.581–5.550)<0.001
TB >4 + CBD dilatation5.738 (2.573–12.794)<0.0011.985 (0.930–4.960)0.074

ASGE, American Society for Gastrointestinal Endoscopy; CI, confidence interval; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct.


Table 4 Comparison between the 2019 ASGE Guidelines and Korean Cutoff Values

2019 ASGEKorean
Cutoff valuesNo. (%)CBD stone
present, No. (%)
Cutoff valuesNo. (%)CBD stone
present, No. (%)
Age, yr>55830 (67.9)212 (25.5)>70 505 (41.3)158 (31.3)
ALP, U/L>110309 (25.3)133 (43.0)>77.5 584 (47.8)210 (36.0)
AST, U/L>45318 (26.0)118 (37.1)>28.5 524 (42.8)178 (34.0)
ALT, U/L>35463 (37.9)164 (35.4)>26.5 504 (41.2)175 (34.7)
GGT, U/L>60516 (42.2)204 (39.5)>82.5 463 (37.9)192 (41.5)
TB, mg/dL +CBD dilatationTB >4 +CBD dilatation26 (2.1)16 (61.5)---
TB, mg/dL--->0.95 477 (39.0)176 (36.9)
CBD dilatation---Present171 (14)138 (49.8)

ASGE, American Society for Gastrointestinal Endoscopy; CBD, common bile duct; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin.


Table 5 Effectiveness of Predictors for Choledocholithiasis Based on Korean Cutoff Value

Clinical predictorSensitivity,%Specificity,%Predictive value, %p-value
PositiveNegative
Age >70 yr57.063.331.383.4<0.001
ALP >77.5 U/L75.860.536.089.5<0.001
AST >28.5 U/L64.363.434.085.8<0.001
ALT >26.5 U/L63.265.234.785.8<0.001
GGT >82.5 U/L69.371.441.588.8<0.001
TB >0.95 mg/dL63.568.236.986.5<0.001
CBD dilatation49.896.580.786.8<0.001

ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct.


Table 6 Odds Ratio of Predictor for Choledocholithiasis Based on Korean Cutoff Value

Clinical predictorUnivariable analysisMultivariable analysis
Odds ratio (95% CI)p-valueOdds ratio (95% CI)p-value
Age >70 yr2.292 (1.746–3.009)<0.0012.117 (1.475–2.705)<0.001
ALP >77.5 U/L4.794 (3.536–6.499)<0.0012.405 (1.386–2.964)<0.001
AST >28.5 U/L3.118 (2.359–4.122)<0.0010.726 (0.639–1.445)0.198
ALT >26.5 U/L3.218 (2.436–4.251)<0.0011.337 (0.870–2.011)0.250
GGT >82.5 U/L5.626 (4.203–7.532)<0.0012.604 (1.910–4.308)<0.001
TB >0.95 mg/dL3.734 (2.821–4.942)<0.0011.415 (2.101–4.382)0.085
CBD dilatation27.468 (18.054–41.789)<0.00124.359 (15.247–39.918)<0.001

CI, confidence interval; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; TB, total bilirubin; CBD, common bile duct.


Table 7 Modeling with Clinical Predictor Odds Ratio, β Coefficients, and Adjusted Scores with Korean Cutoff Value

PredictorOdds ratio (95% CI)p-valueβAdjusted score
Intercept–3.263
Age >70 yr2.119 (1.500–2.994)<0.0010.7511.0
GGT >82.5 U/L2.962 (1.969–4.456)<0.0011.0861.4
ALP >77.5 U/L2.470 (1.600–3.812)<0.0010.9041.2
CBD dilatation24.850 (15.657–39.440)<0.0013.2134.2

CI, confidence interval; GGT, gamma-glutamyl transferase; ALP, alkaline phosphatase; CBD, common bile duct.


Table 8 Assessing the Utility of Korean Criteria Risk Stratification

RiskScorePrevalence, No. (%)CBD stone, No. (%)p-valueSensitivity, %Specificity, %LHR+LHR–
Present (n=277)Absent (n=946)
Low<1.0343 (28.1)14 (4.1)329 (95.9)<0.00194.934.81.460.15
Intermediate1.0–5.5755 (61.7)149 (19.7)606 (80.7)<0.00153.835.90.841.79
High>5.5125 (10.2)114 (91.2)11 (8.8)<0.00141.298.834.330.60

CBD, common bile duct; LHR+, likelihood ratio positive; LHR–, likelihood ratio negative.


Table 9 Assessing the Utility of ASGE Criteria Risk Stratification

RiskPrevalence, No. (%)CBD stone, No. (%)p-valueSensitivity, %Specificity, %LHR+LHR–
Present (n=277)Absent (n=946)
Low188 (15.4)2 (1.1)186 (98.9)<0.00199.319.71.240.04
Intermediate905 (74.0)155 (17.1)750 (82.9)<0.00156.020.70.713.83
High130 (10.6)120 (92.3)10 (7.7)<0.00143.398.939.360.57

ASGE, American society for Gastrointestinal Endoscopy; CBD, common bile duct; LHR+, likelihood ratio positive; LHR–, likelihood ratio negative.


References

  1. Gallaher JR, Charles A. Acute cholecystitis: a review. JAMA 2022;327:965-975.
    Pubmed CrossRef
  2. Ukegjini K, Schmied BM. Diagnosis and treatment of acute cholecystitis. Ther Umsch 2020;77:133-146.
    Pubmed CrossRef
  3. Zong Y, Stanger BZ. Molecular mechanisms of bile duct development. Int J Biochem Cell Biol 2011;43:257-264.
    Pubmed KoreaMed CrossRef
  4. Freitas ML, Bell RL, Duffy AJ. Choledocholithiasis: evolving standards for diagnosis and management. World J Gastroenterol 2006;12:3162-3167.
    Pubmed KoreaMed CrossRef
  5. Buxbaum JL, Abbas Fehmi SM, et al; ASGE Standards of Practice Committee. ASGE guideline on the role of endoscopy in the evaluation and management of choledocholithiasis. Gastrointest Endosc 2019;89:1075-1105.
    Pubmed KoreaMed CrossRef
  6. Portincasa P, Di Ciaula A, de Bari O, Garruti G, Palmieri VO, Wang DQ. Management of gallstones and its related complications. Expert Rev Gastroenterol Hepatol 2016;10:93-112.
    Pubmed CrossRef
  7. Depew WT. Endoscopic retrograde cholangiopancreatography. Can Med Assoc J 1981;125:531-533.
    Pubmed KoreaMed CrossRef
  8. Tanaka M, Ikeda S, Nakayama F. Change in bile duct pressure responses after cholecystectomy: loss of gallbladder as a pressure reservoir. Gastroenterology 1984;87:1154-1159.
    Pubmed CrossRef
  9. Kedia P, Tarnasky PR. Endoscopic management of complex biliary stone disease. Gastrointest Endosc Clin N Am 2019;29:257-275.
    Pubmed CrossRef
  10. Rácz I, Rejchrt S, Hassan M. Complications of ERCP: ethical obligations and legal consequences. Dig Dis 2008;26:49-55.
    Pubmed CrossRef
  11. Afzalpurkar S, Giri S, Kasturi S, Ingawale S, Sundaram S. Magnetic resonance cholangiopancreatography versus endoscopic ultrasound for diagnosis of choledocholithiasis: an updated systematic review and meta-analysis. Surg Endosc 2023;37:2566-2573.
    Pubmed CrossRef
  12. Toro-Calle J, Guzmán-Arango C, Ramírez-Ceballos M, Guzmán-Arango N. Are the ASGE criteria sufficient to stratify the risk of choledocholithiasis?. Rev Colomb Gastroenterol 2020;35:304-310.
    CrossRef
  13. He H, Tan C, Wu J, et al. Accuracy of ASGE high-risk criteria in evaluation of patients with suspected common bile duct stones. Gastrointest Endosc 2017;86:525-532.
    Pubmed CrossRef
  14. Yang MH, Chen TH, Wang SE, et al. Biochemical predictors for absence of common bile duct stones in patients undergoing laparoscopic cholecystectomy. Surg Endosc 2008;22:1620-1624.
    Pubmed CrossRef
  15. Carriere V, Conway J, Evans J, Shokoohi S, Mishra G. Which patients with dilated common bile and/or pancreatic ducts have positive findings on EUS?. J Interv Gastroenterol 2012;2:168-171.
    Pubmed KoreaMed CrossRef
  16. Lee YN, Moon JH. Optimal predictive criteria for common bile duct stones: the search continues. Clin Endosc 2021;54:147-148.
    Pubmed KoreaMed CrossRef
  17. Tse F, Liu L, Barkun AN, Armstrong D, Moayyedi P. EUS: a meta-analysis of test performance in suspected choledocholithiasis. Gastrointest Endosc 2008;67:235-244.
    Pubmed CrossRef
  18. Ragulin-Coyne E, Witkowski ER, Chau Z, et al. Is routine intraoperative cholangiogram necessary in the twenty-first century? A national view. J Gastrointest Surg 2013;17:434-442.
    Pubmed KoreaMed CrossRef
  19. Jacob JS, Lee ME, Chew EY, Thrift AP, Sealock RJ. Evaluating the revised American Society for Gastrointestinal Endoscopy Guidelines for common bile duct stone diagnosis. Clin Endosc 2021;54:269-274.
    Pubmed KoreaMed CrossRef
  20. Mark DH, Flamm CR, Aronson N. Evidence-based assessment of diagnostic modalities for common bile duct stones. Gastrointest Endosc 2002;56(6 Suppl):S190-S194.
    Pubmed CrossRef
  21. Tazuma S. Gallstone disease: epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic). Best Pract Res Clin Gastroenterol 2006;20:1075-1083.
    Pubmed CrossRef
  22. Stinton LM, Myers RP, Shaffer EA. Epidemiology of gallstones. Gastroenterol Clin North Am 2010;39:157-169.
    Pubmed CrossRef
  23. Hu KC, Chu CH, Wang HY, et al. How does aging affect presentation and management of biliary stones?. J Am Geriatr Soc 2016;64:2330-2335.
    Pubmed CrossRef
  24. Vacca G, Reginelli A, Urraro F, et al. Magnetic resonance severity index assessed by T1-weighted imaging for acute pancreatitis: correlation with clinical outcomes and grading of the revised Atlanta classification-a narrative review. Gland Surg 2020;9:2312-2320.
    Pubmed KoreaMed CrossRef
Gut and Liver

Vol.18 No.3
May, 2024

pISSN 1976-2283
eISSN 2005-1212

qrcode
qrcode

Supplementary

Share this article on :

  • line

Popular Keywords

Gut and LiverQR code Download
qr-code

Editorial Office