Keywords
cholecystectomy, gallstones, lipid profile, dyslipidemia, LDL, cholesterol, Atherogenic Index of Plasma
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Alatrash M, Moustafa MS, Nashed GA et al. Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease: A Prospective, Single-Arm, Before-After Study [version 1; peer review: awaiting peer review]. F1000Research 2025, 14:1474 (https://doi.org/10.12688/f1000research.174454.1)
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Research Article
Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease: A Prospective, Single-Arm, Before-After Study
[version 1; peer review: awaiting peer review]
PUBLISHED 30 Dec 2025
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Abstract
Corresponding author:
Mohamed Alatrash
Competing interests:
No competing interests were disclosed.
Grant information:
The author(s) declared that no grants were involved in supporting this work.
Copyright:
© 2025 Alatrash M et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Alatrash M, Moustafa MS, Nashed GA et al. Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease: A Prospective, Single-Arm, Before-After Study [version 1; peer review: awaiting peer review]. F1000Research 2025, 14:1474 (https://doi.org/10.12688/f1000research.174454.1)
First published: 30 Dec 2025, 14:1474 (https://doi.org/10.12688/f1000research.174454.1)
Latest published: 30 Dec 2025, 14:1474 (https://doi.org/10.12688/f1000research.174454.1)
Introduction
The gallbladder plays an essential role in the digestion and absorption of lipids by concentrating and storing hepatic bile, which is crucial for lipid homeostasis.1 Gallstone disease is a common gastrointestinal condition, affecting approximately 10-15% of adults in the United Kingdom, and represents a significant health and economic burden.2 Beyond its local symptoms, recent evidence suggests that gallstone disease may be associated with systemic conditions, including cardiovascular disease and a higher overall mortality, highlighting its broader health implications.2 Cholecystectomy, the surgical removal of the gallbladder, is one of the most frequently performed surgical procedures worldwide and is generally considered a safe procedure with minimal impact on overall metabolic regulation.3,4
The absorption of cholesterol is primarily facilitated by the action of bile salts and phospholipids. An imbalance, such as an excess of cholesterol or a deficiency in bile salts or phospholipids, can lead to the crystallization of cholesterol and the formation of gallstones.5,6 It has been hypothesized that post-cholecystectomy, a reduction in the bile acid pool size and an increase in the frequency of enterohepatic circulation may alter the lipid profile of patients. This study was therefore designed to investigate the impact of cholecystectomy on blood lipid levels.
The primary objective of this study was to evaluate the change in serum lipid levels—including low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, triglycerides, and very low-density lipoprotein (VLDL)—from baseline to 6 months after cholecystectomy. The secondary objectives were to assess changes in the proportion of patients with abnormal lipid values and to evaluate changes in cardiovascular risk markers, such as the Atherogenic Index of Plasma (AIP) and the total cholesterol/HDL ratio.
An earlier version of this work was posted online as a preprint.15 This work is licensed under a CC BY 4.0 License.
Materials and methods
Study design and patients
This prospective, single-arm, before-after study was conducted on 40 adult patients with symptomatic gallstone disease who underwent laparoscopic cholecystectomy. Patients were recruited from the General Surgery department at Cairo University Hospital between August 2022 and March 2023. The study was designed to evaluate the impact of cholecystectomy on lipid profiles by comparing preoperative measurements with those taken at a 6-month postoperative follow-up.
Inclusion and exclusion criteria
The criteria for patient selection are summarized in Table 1. Patients included were adults aged 18–65 years with documented symptomatic gallstone disease, who were able and willing to provide informed consent and comply with follow-up requirements. Exclusion criteria included acute cholecystitis at the time of evaluation, pregnancy or lactation, use of lipid-lowering medications, or known metabolic disorders affecting lipid metabolism.
Table 1. Inclusion and exclusion criteria for patient selection.
Ethical considerations
The study was approved by the Cairo University Faculty of Medicine Research Ethics Committee (Approval No. MS-213-2022). All procedures were conducted in accordance with institutional guidelines and the Declaration of Helsinki. Written informed consent was obtained from each participant. Patient privacy was protected; all data were kept confidential and no personal identifiers are revealed in this report.
Preoperative and postoperative assessments
All patients underwent a thorough preoperative evaluation, including documentation of baseline demographic data (age, sex, weight, body mass index [BMI]) and clinical history. A fasting blood sample (>12 hours) was obtained at least one day before surgery to measure the baseline lipid profile.
Patients were followed up in the outpatient clinic, and at approximately 6 months postoperatively, a follow-up fasting lipid profile was obtained using the same methods as the preoperative testing. The 6-month interval was chosen to allow for the stabilization of any transient postoperative changes and to assess intermediate-term effects. All 40 patients returned for the 6-month blood test, representing a 100% follow-up rate. Patients were advised to maintain their usual diet and lifestyle during the follow-up period, and none initiated lipid-lowering therapy.
Lipid profile and other measurements
Serum triglycerides and total cholesterol were measured using standard enzymatic colorimetric assays. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured using direct homogeneous enzymatic methods.7 Liver function tests, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), as well as a complete blood count and creatinine, we also measured preoperatively and postoperatively.
Study outcomes and statistical analysis
The primary outcome was the change in serum lipid levels (LDL, HDL, total cholesterol, triglycerides, VLDL) from baseline to 6 months after cholecystectomy. Secondary outcomes included the change in the proportion of patients with abnormal lipid values (pre- vs. postoperatively) and changes in the Atherogenic Index of Plasma (AIP) and the total cholesterol/HDL ratio.8
Data were analyzed using IBM SPSS Statistics version 25.0 (Armonk, NY: IBM Corp). Continuous variables were tested for normality using the Kolmogorov-Smirnov test. Normally distributed data are presented as mean ± standard deviation (SD), while non-normally distributed data are presented as median and interquartile range (IQR). Categorical variables are summarized as number (percentage). For paired comparisons of pre- and postoperative measurements, the paired Student’s t-test was used for parametric data, and the Wilcoxon signed-rank test was used for non-parametric data. The McNemar test was used to compare paired categorical data (e.g., the proportion of patients with abnormal values before vs. after surgery). A two-tailed p-value < 0.05 was considered statistically significant. No formal sample size calculation was performed prior to the study, which is a limitation. A post-hoc power analysis was planned to evaluate whether the sample of 40 patients was sufficient to detect clinically meaningful changes in lipids.
Results
Patient demographics
The study included 40 patients, of whom 30 (75%) were female. The mean age was 42.1 ± 8.9 years, and the mean Body Mass Index (BMI) was 30.2 ± 2.9 kg/m2, indicating that the study population was, on average, overweight. The basic demographic characteristics of the patients are summarized in Table 2.
Table 2. Basic demographic characteristics of patients (n=40).
Preoperative lipid profile
Preoperatively, a high proportion of patients exhibited dyslipidemia based on the Adult Treatment Panel III (ATP III) criteria. As shown in Table 3, 25 patients (62.5%) had elevated total cholesterol (≥200 mg/dL), and 34 patients (85%) had elevated LDL cholesterol (≥100 mg/dL). Low HDL cholesterol was also common, observed in 16 of 30 females (53.3%) and 1 of 10 males (10%). Hypertriglyceridemia (triglycerides ≥150 mg/dL) was present in 16 patients (40%).
Table 3. Number and percentage of individuals with abnormal lipid profile levels preoperatively (n=40).
Changes in lipid profile postoperatively
As summarized in Table 4, cholecystectomy was associated with statistically significant improvements in several key lipid parameters at the 6-month follow-up. Mean LDL cholesterol decreased by approximately 4.5% (from 128.7 ± 34.3 to 122.9 ± 31.6 mg/dL; p = 0.002), and mean total cholesterol decreased by approximately 5.5% (from 206.0 ± 37.1 to 194.8 ± 33.7 mg/dL; p = 0.003). Mean VLDL cholesterol also showed a modest but significant reduction (25.2 ± 7.7 to 23.6 ± 7.8 mg/dL; p = 0.031). The total cholesterol/HDL ratio, a marker of cardiovascular risk, also improved significantly, decreasing from a mean of 4.60 ± 1.29 to 4.35 ± 1.17 (p = 0.004).
Table 4. Comparison of lipid profile parameters preoperatively and postoperatively (n=40).
In contrast, there were no statistically significant changes in mean HDL cholesterol levels (46.4 ± 6.6 vs. 46.2 ± 6.2 mg/dL; p = 0.515) or median triglyceride levels (134 vs. 130.5 mg/dL; p = 0.381). The Atherogenic Index of Plasma (AIP) also remained essentially unchanged (p = 0.216).
Proportion of patients with abnormal lipid profiles postoperatively
Despite the significant improvements in mean lipid levels, the proportion of patients with dyslipidemia did not change substantially after surgery. As shown in Table 5, the percentage of patients with high total cholesterol dropped from 62.5% preoperatively to 47.5% postoperatively (p=0.07). However, the proportion of patients with high LDL (85% vs. 85%; p=1.00) and low HDL (42.5% vs. 42.5%; p=1.00) remained unchanged. There was a non-significant decrease in the proportion of patients with high triglycerides (40% vs. 37.5%; p=1.00).
Table 5. Proportion of patients with abnormal lipid profiles before and after cholecystectomy (n=40).
Other laboratory findings
There were significant postoperative decreases in the liver enzymes alkaline phosphatase (ALP) (mean 87.8 → 73.3 IU/L; p = 0.005) and gamma-glutamyl transferase (GGT) (mean 46.3 → 38.1 IU/L; p = 0.001). The total leukocyte count (TLC) also showed a significant reduction (mean 8.43 → 7.40 ×109/L; p = 0.02). Other laboratory parameters, including hemoglobin, AST, ALT, creatinine, and INR, did not show significant changes.
Discussion
In this prospective, single-arm, before-after study of 40 patients with symptomatic gallstone disease, we observed that cholecystectomy was associated with a modest but statistically significant improvement in serum lipid profile over a 6-month follow-up. Specifically, there were significant reductions in mean LDL cholesterol, total cholesterol, and VLDL cholesterol, whereas triglyceride and HDL levels did not change significantly. These findings suggest a potential metabolic benefit of gallbladder removal in terms of cholesterol reduction, but also highlight that the effect size is modest. For example, the observed ~5.5% reduction in total cholesterol is substantially less than what is typically achieved with pharmacological therapy or intensive lifestyle modifications for dyslipidemia. For context, statins can lower LDL cholesterol by 20-55%, which translates to a significant reduction in all-cause mortality and a 20-25% reduction in major cardiovascular events.9 In our study, the LDL drop was only ~6 mg/dL on average, which, while statistically significant, may have limited clinical impact on long-term cardiovascular risk.
Our results are generally consistent with several recent studies that have reported improvements in lipid profiles after cholecystectomy. For instance, Singh et al. (2024) found significant postoperative decreases in total cholesterol, LDL, and triglycerides, and an increase in HDL at 1 month, in a larger cohort of 72 patients.10 Similarly, Reddy et al. (2022) observed a significant decrease in total cholesterol, LDL, TGL, and VLDL, and an increase in HDL post-cholecystectomy, with HDL increasing significantly.11 The improvements observed in our study with respect to LDL and total cholesterol align with these findings, confirming that gallbladder removal can positively influence lipid metabolism, at least in the short-to-intermediate term. However, our study did not show significant changes in HDL or triglycerides, which may be due to population differences, the smaller sample size, or the longer follow-up period.
On the other hand, there are studies with conflicting results. Farrugia et al. (2024), who conducted a rigorous case-control study with a 1-year follow-up, reported no significant differences in lipid profiles after cholecystectomy, but a significant increase in triglycerides.12 The difference between Farrugia's findings and ours may be attributable to the use of a control group in their study, which provides a more robust comparison. The mechanisms by which cholecystectomy affects lipid metabolism are not fully elucidated. One hypothesis is that the removal of the gallbladder, a bile reservoir, leads to a continuous trickle of bile into the intestine rather than a coordinated pulsatile release after meals, thereby disrupting normal bile storage and controlled postprandial release.13 This change could alter enterohepatic circulation of bile acids. Indeed, some studies have shown that bile acid synthesis is increased after cholecystectomy.14 Because bile acid synthesis consumes cholesterol, this could explain the reduction in total and LDL cholesterol observed in our study.
From a clinical perspective, our findings do not support the idea of cholecystectomy as a treatment for dyslipidemia per se. The improvements in LDL and total cholesterol, while statistically significant, were modest and may not meet thresholds for clinically meaningful risk reduction. No patient in our study achieved a complete normalization of their lipid profile on the basis of surgery if they were significantly dyslipidemic beforehand. Therefore, cholecystectomy should not be viewed as a therapeutic intervention for dyslipidemia. Rather, for patients requiring cholecystectomy for symptomatic gallstones, there might be a side benefit of slight lipid improvement or at least no worsening of lipid profile on average. This could be a useful point in patient counseling—for instance, patients often ask if gallbladder removal will affect their weight or cholesterol; we can inform them that on average their cholesterol might actually decline a bit.
An earlier version of this work was posted online as a preprint.15
Despite these insights, our study has several limitations. First, the sample size of 40 patients is relatively small, which may limit the statistical power and generalizability of the results. Second, we did not include a control group of patients with gallstones who did not undergo surgery, which makes it difficult to distinguish the effects of surgery from the natural course of the disease or other secular changes. Third, the follow-up period of 6 months is relatively short and does not allow for an assessment of the long-term effects of cholecystectomy. Finally, we did not collect detailed data on dietary habits, physical activity, or other lifestyle factors post-surgery; as such, these factors could influence lipid levels independently of the surgery and were not accounted for in our analysis. These limitations should be considered when interpreting our findings, and they highlight the need for larger, controlled studies with longer follow-up and comprehensive lifestyle data to fully elucidate the impact of cholecystectomy on lipid metabolism.
Conclusions
In this prospective, single-arm, before-after study, cholecystectomy was found to be associated with statistically significant reductions in mean total cholesterol and LDL levels at 6 months postoperatively, without a notable impact on triglycerides or HDL. This suggests a modest, but favorable, short-term effect on the lipid profile in patients with symptomatic gallstone disease. However, the magnitude of this improvement was small and did not translate into a significant reduction in the proportion of patients with dyslipidemia. Cholecystectomy should not be considered a treatment for dyslipidemia, but patients can be counseled that their cholesterol may improve slightly after the surgery. Larger, controlled studies with longer follow-up are required to confirm these findings and determine their clinical significance for cardiovascular risk reduction.
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how to cite this article
Alatrash M, Moustafa MS, Nashed GA et al. Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease: A Prospective, Single-Arm, Before-After Study [version 1; peer review: awaiting peer review]. F1000Research 2025, 14:1474 (https://doi.org/10.12688/f1000research.174454.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Version 1
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PUBLISHED 30 Dec 2025
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Reader Comment 10 Jan 2026Massimo Chiaretti, Dipartimento di Chirurgia Generale e Specialistica P Stefanini, Universita degli Studi di Roma La Sapienza Dipartimento di Chirurgia Generale e Specialistica P Stefanini, Rome, Italy10 Jan 2026Reader CommentDear Colleagues, in the paper's discussion it is written: "One hypothesis is that removal of the gallbladder, a bile reservoir, leads to a continuous flow of bile into the intestine ... Continue reading
Yes, this is all understandable, but downstream of the duodenum, after laparoscopic cholecystectomy, there is usually no intestinal fistula (cause of bile acid leakage). Therefore, we observe only a slight loss of bile acids because bile is continuously trickled into the intestine rather than released in a coordinated manner during meals, and we sometimes see diarrhea or increased bowel movements with creamy stools. The liver produces bile and its bile acids. Please also consider that all symptomatic patients who have undergone surgery for cholesterol stones are instructed to reduce their saturated fat intake and replace it with polyunsaturated fats of vegetable origin postoperatively. Modifying feeding can reduce lipoproteins, triglycerides, and cholesterol.
Yes, this is all understandable, but downstream of the duodenum, after laparoscopic cholecystectomy, there is usually no intestinal fistula (cause of bile acid leakage). Therefore, we observe only a slight loss of bile acids because bile is continuously trickled into the intestine rather than released in a coordinated manner during meals, and we sometimes see diarrhea or increased bowel movements with creamy stools. The liver produces bile and its bile acids. Please also consider that all symptomatic patients who have undergone surgery for cholesterol stones are instructed to reduce their saturated fat intake and replace it with polyunsaturated fats of vegetable origin postoperatively. Modifying feeding can reduce lipoproteins, triglycerides, and cholesterol.