Gallstone disease is a common gastrointestinal condition affecting 10–20% of adults in developed countries and around 4% in India, contributing significantly to illness and sometimes even death.1 Understanding its prevalence and risk factors—such as older age, female gender, obesity, and a sedentary lifestyle—can help guide clinical practice and research efforts.²⁻⁴

A significant concern arises when gallstones migrate into the common bile duct (CBD), a condition called choledocholithiasis, which may cause serious complications such as cholangitis, pancreatitis, or even liver damage.⁵ While some patients show clear symptoms, others may remain asymptomatic, making diagnosis difficult.⁶⁻⁸ If CBD stones are missed and only the gallbladder is removed, residual stones can lead to complications.⁹

Therefore, identifying choledocholithiasis before surgery is critical.¹⁰⁻¹¹ Diagnosis typically involves blood tests and imaging like ultrasound, MRCP, or EUS.¹² If CBD stones are found, they often require removal, with ERCP being a common but invasive option.¹³⁻¹⁹ In practice, liver function tests such as GGT and ALP may offer clues, as elevations in these enzymes are frequently observed in biliary tract disorders.20-22

Although imaging studies like MRCP are highly specific, they may not always be available or cost-effective in resource-limited settings. This highlights the importance of reliable, accessible biochemical markers to assist in early detection. Enzyme levels such as GGT and ALP are commonly evaluated in hepatobiliary disorders, but their comparative sensitivity and diagnostic value in choledocholithiasis still require further exploration.23,24 Establishing a clear correlation could improve early diagnosis and reduce the risk of missed or delayed treatment. Therefore, this study aims to compare GGT and ALP as diagnostic markers in choledocholithiasis, exploring their accuracy and reliability in early detection.

This study was conducted over a period of two years (August 2020 to August 2022) at the Departments of General Surgery and Gastroenterology, Fortis Hospital, Noida, Uttar Pradesh. It was a hospital-based, retrospective and prospective comparative study involving 100 patients who presented with symptoms suggestive of choledocholithiasis. Patients were included after obtaining ethical clearance and informed consent. The inclusion criteria focused on patients clinically suspected of choledocholithiasis, while individuals with conditions or comorbidities that could affect liver enzyme levels—such as viral hepatitis, chronic alcoholism, metabolic or endocrine disorders, bone diseases, or certain medications—were excluded to avoid confounding the results.

Detailed clinical histories and physical examinations were conducted for all enrolled participants. Liver function tests, specifically serum Gamma Glutamyl Transferase (GGT) and Alkaline Phosphatase (ALP), were measured using standardized biochemical methods. Data collection was followed by statistical analysis using SPSS version 22.0. Results were expressed as mean ± standard deviation, and the diagnostic accuracy of GGT and ALP was evaluated using Receiver Operating Characteristic (ROC) curve analysis. Comparisons between markers were assessed using the Z-test, and a p-value of less than 0.05 was considered statistically significant.

Table 1: Gender distribution among the study subjects

The present study was conducted at General surgery department and Gastroenterology department in the Fortis hospital, Noida, Uttar Pradesh for a duration of 2 years (August 2020 to August 2022). 100 patients with symptoms of Choledocholithiasis were taken for this study. Females (62%) were comparatively more as compared to males (38%) in this study (table 1, graph 1).

Table 2: Co-morbidities among the study subjects

Table 2, graph 2 shows the co-morbidities among the study subjects. Co-morbidities viz. hypertension, diabetes and hyperlipidemia was present in 16%, 24% and 9% of the subjects respectively.

Table 3: Symptoms among the study subjects

Table 4: Murphy’s sign among the study subjects

Table 5: Symptoms and Signs among the study subjects

GRAPH 5: Signs among the study subjects

Itching, change in stool color, change in urine color and cholangitis was present among 7%, 11%, 28% and 9% of the subjects respectively (table 5, graph 5).

Table 6: Distribution of alkaline phosphatase (ALP) and Gamma glutamyl transpeptidase (GGT) among the study subjects

Table 7: Descriptive analysis of alkaline phosphatase (ALP) and Gamma glutamyl transpeptidase (GGT) among the study subjects

Table 8: Analysis of receiver operating characteristic curve

                              *: statistically significant, **: highly significant

Gall stone disease is one of the most common health-related problems today, which is associated with significant morbidity and sometimes even mortality. In present study, a female preponderance was seen among the study participants, with nearly 62% participants being females, and only 38% being males. This is congruent to findings of Yong Mei et al25 and Gill MPS et al26 which also revealed more females as compared to males. According to Schwartz’s Principles of Surgery, gallstone disease is three times more common in women than men27. Thus choledocholithiasis is also common in women. In our study also, choledocholithiasis is 1.8 times more common in females than males. However, in a study by James Yurgaky-Sarmiento et al28, male preponderance was found. This difference might be due to difference in study area and design.

 In the present study, mean age among the study subjects was found to be 51.48±9.23 years. In a study by Gill MPS et al26, mean age among the study subjects was 48 years, which is approximately similar to our study. Similar age distribution was reported by Yong Mei et al25 in their study. According to the latest literature, cholelithiasis is occurring in younger patients year by year, with a significant increase in adolescents (< 20 years old). This may be related to obesity, lack of exercise, diabetes and early pregnancy.27 In the present study the occurrence of cholelithiasis and choledocholithiasis was more  in younger age (62% in age less than 50 years)  compared to older age (38% in age more than 50 years).

In the present study, diabetes mellitus was seen in 24% of the patients, hypertension was seen in 16% of the patients, and hyperlipidemia was seen in 9% of the patients. A similar distribution of co-morbidities was revealed among their study subjects of Yong Mei et al25.

In the present study, there was presence of right upper quadrant pain in 40% patients, mid epigastric pain in 23% patients, and a combination of both right upper quadrant and mid-epigastric abdominal pain in 37% of the patients. In the present study, it was observed that 7% patients had itching, 11% had a change in color of the stool, 28% had a change in color in urine, and 9% had symptoms suggestive of cholangitis. Also, in the current study, murphy’s sign was positive in 12% of the subjects. M. S. Padda et al29 in their study also found that right upper quadrant pain was the predominant symptom on admission. However, in their study, Murphy’s sign was absent in a substantial proportion (around 92%) of patients. This was attributed to the fact that most patients had already received analgesics prescribed by a physician, before abdominal examination could be conducted by the surgeon.

The results of this study showed that serum GGT and ALP levels were higher in the patients with diagnosis of choledocholithiasis. Abnormal ALP was seen in 83% patients and an abnormal GGT was found among 89% of the patients. Mean ALP and GGT level among the study subjects was 168.52±13.29 U/L and 153.47±22.91 U/L respectively. Sensitivity and specificity of ALP was 0.68 and 0.67, sensitivity and specificity of GGT was 0.89 and 0.82 respectively. Hence, in this study, GGT predicted choledocholithiasis better as compared to ALP with AUC of 0.86.

Singh MK et al24 in their study showed that GGT is more useful as compared to ALP in obstructive biliary diseases. According to Sapey T et al23, GGT shows a higher elevation in patients with cholestasis, which is even more marked in extra-hepatic cholestasis. According to Stein TA et al30, GGT is more responsive to biliary obstruction than other liver enzymes like Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALP), and being more specific it is helpful in working up elevated levels of ALP. Similarly, Yong Mei et al25 in their study found that serum GGT and ALP levels were significantly higher in the group with asymptomatic secondary choledocholithiasis. The sensitivity and specificity of ALP in their study was found to be 65.1% and 59.8% respectively, while that of GGT was found to be 90.8% and 83.6% respectively. The sensitivity and specificity of a combination of both GGT and ALP were 93.5% and 85.1%, respectively.

The present study indicates that changes in the serum levels of ALP and GGT are also related to asymptomatic choledocholithiasis, and an abnormal increase of these indicators may be a risk factor for choledocholithiasis. It also indicated that an abnormal increase in serum GGT plays an important role in predicting cholelithiasis combined with secondary asymptomatic choledocholithiasis and it may be an effective serological index for routine screening. With the exception of obvious jaundice, a raised GGT level has been suggested to be the most sensitive and specific indicator of CBD stones31. There are two reasons for increased GGT - firstly, the presence of stones may cause local inflammatory damage to the bile duct epithelium, resulting in excessive GGT production, and secondly, the presence of stones has a mechanical stimulatory effect on the bile duct epithelium, inducing the epithelial layer to increase GGT synthesis, combined with poor bile excretion, eventually leading to an abnormal increase in serum GGT. Therefore, the latest literature suggests that serum GGT is also an inflammatory marker31.

Therefore, in cases where the GGT exceeds the cutoff level in serum liver function in gallstone patients, we should be vigilant that the patient may be afflicted with secondary asymptomatic choledocholithiasis, and thus MRCP or ERCP examination should be performed to confirm the diagnosis. This can avoid biliary tract inflammatory disease or tissue malignant transformation caused by the long-term presence of asymptomatic choledocholithiasis. A suitable surgical plan can also be developed to prevent intraoperative accidents, serious postoperative complications and other risks due to missed diagnosis.

The limitation of the present study was a relatively small sample size and a lack of control group. Another limitation is that this was a single-center study; however, this type of study in our environment may involve variables that are difficult to control given the inter-observer variability in interpretation of imaging techniques, and the unavailability of experts in resonance cholangiography, echo-endoscopy and ERCP.

In conclusion abnormally elevated serum GGT level may be a potentially useful marker for the early prediction of choledocholithiasis secondary to cholelithiasis. When the serum GGT level reaches the cutoff value, physicians should be vigilant about the possibility of secondary choledocholithiasis, timely and proper interventions should be performed to avoid aggravation of the disease. As a convenient, rapid and inexpensive test, it is worth applying this test in routine screening of cholelithiasis and suspected choledocholithiasis.

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