Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease: A Prospective, Single-Arm, Before-After Study

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Gallstone disease is frequently associated with dyslipidemia, and cholecystectomy is one of the most common abdominal surgeries worldwide. However, its influence on serum lipid metabolism remains incompletely understood. Objective To evaluate changes in serum lipid profiles six months after cholecystectomy and assess whether the procedure contributes to improvement of dyslipidemia. Methods A prospective cohort study was conducted on 40 adult patients undergoing laparoscopic cholecystectomy for symptomatic gallstone disease between August 2024 and March 2025. Fasting lipid profiles—including LDL-cholesterol, HDL-cholesterol, triglycerides, total cholesterol, and VLDL—were measured preoperatively and at 6-month follow-up. The Atherogenic Index of Plasma (AIP) and total cholesterol/HDL ratio were calculated. Statistical analysis was performed using paired tests with significance set at p < 0.05. Results Significant reductions were observed in total cholesterol (206.0 ± 37.1 to 194.8 ± 33.7 mg/dL, p = 0.003), LDL-cholesterol (128.7 ± 34.3 to 122.9 ± 31.6 mg/dL, p = 0.002), VLDL (25.2 ± 7.7 to 23.6 ± 7.8 mg/dL, p = 0.031), and the total cholesterol/HDL ratio (p = 0.004). HDL and triglyceride levels showed no significant change. AIP remained stable. Improvements were statistically significant but modest in magnitude. Conclusions Cholecystectomy was associated with small but significant reductions in total cholesterol and LDL-cholesterol six months postoperatively. Although the procedure is not a treatment for dyslipidemia, these findings suggest no adverse impact on lipid metabolism, and possibly a slight beneficial effect. 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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. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ 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: 2 approved with reservations] Mohamed Alatrash https://orcid.org/0009-0001-2638-8360 1 , Mohamed Saber Moustafa 1 , George Abdelfady Nashed 1 , George Mosaad 1 , Mahmoud Dewair 1 Mohamed Alatrash https://orcid.org/0009-0001-2638-8360 1 , Mohamed Saber Moustafa 1 , [...] George Abdelfady Nashed 1 , George Mosaad 1 , Mahmoud Dewair 1 PUBLISHED 30 Dec 2025 Author details Author details 1 Cairo University Kasr Alainy Faculty of Medicine, Cairo, Cairo Governorate, Egypt Mohamed Alatrash Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Mohamed Saber Moustafa Roles: Data Curation, Formal Analysis, Investigation, Methodology, Resources, Supervision, Validation, Writing – Review & Editing George Abdelfady Nashed Roles: Conceptualization, Investigation, Methodology, Project Administration, Supervision, Writing – Review & Editing George Mosaad Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Project Administration, Visualization, Writing – Original Draft Preparation Mahmoud Dewair Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background The gallbladder plays an essential role in lipid homeostasis through bile storage and regulated release. Gallstone disease is frequently associated with dyslipidemia, and cholecystectomy is one of the most common abdominal surgeries worldwide. However, its influence on serum lipid metabolism remains incompletely understood. Objective To evaluate changes in serum lipid profiles six months after cholecystectomy and assess whether the procedure contributes to improvement of dyslipidemia. Methods A prospective cohort study was conducted on 40 adult patients undergoing laparoscopic cholecystectomy for symptomatic gallstone disease between August 2024 and March 2025. Fasting lipid profiles—including LDL-cholesterol, HDL-cholesterol, triglycerides, total cholesterol, and VLDL—were measured preoperatively and at 6-month follow-up. The Atherogenic Index of Plasma (AIP) and total cholesterol/HDL ratio were calculated. Statistical analysis was performed using paired tests with significance set at p < 0.05. Results Significant reductions were observed in total cholesterol (206.0 ± 37.1 to 194.8 ± 33.7 mg/dL, p = 0.003), LDL-cholesterol (128.7 ± 34.3 to 122.9 ± 31.6 mg/dL, p = 0.002), VLDL (25.2 ± 7.7 to 23.6 ± 7.8 mg/dL, p = 0.031), and the total cholesterol/HDL ratio (p = 0.004). HDL and triglyceride levels showed no significant change. AIP remained stable. Improvements were statistically significant but modest in magnitude. Conclusions Cholecystectomy was associated with small but significant reductions in total cholesterol and LDL-cholesterol six months postoperatively. Although the procedure is not a treatment for dyslipidemia, these findings suggest no adverse impact on lipid metabolism, and possibly a slight beneficial effect. READ ALL READ LESS Keywords cholecystectomy, gallstones, lipid profile, dyslipidemia, LDL, cholesterol, Atherogenic Index of Plasma Corresponding Author(s) Mohamed Alatrash ( [email protected] ) Close 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: 2 approved with reservations] . 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. Inclusion criteria Exclusion criteria Aged 18–65 years, with symptomatic gallbladder disease (e.g., recurrent biliary colic, nausea, right upper quadrant pain) Acute cholecystitis at the time of evaluation (e.g., positive Murphy’s sign, fever, palpable RUQ mass, persistent severe pain > 48 hours, leukocytosis) Documented gallstones on ultrasound (or radiologic signs of gallbladder inflammation) Pregnancy or lactation Able and willing to participate in the study and comply with follow-up requirements On lipid-lowering medications or on a restrictive diet (e.g., vegetarian) known to affect lipid levels Provided informed consent for surgery and study participation Known metabolic disorders or comorbid conditions affecting lipid metabolism (e.g., untreated hypothyroidism) History of hepatobiliary malignancy or other severe systemic illness Psychologically unable to consent or participate in long-term follow-up Refusal to undergo cholecystectomy 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/m 2 , 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). Parameter Value Gender Male: 10 (25%); Female: 30 (75%) Age (years) Mean ± SD: 42.1 ± 8.9; Median [IQR]: 42.5 [36–48.5] Weight (kg) Mean ± SD: 81.9 ± 8.7; Median [IQR]: 82 [78–87.5] BMI (kg/m 2 ) Mean ± SD: 30.2 ± 2.9; Median [IQR]: 29.9 [28.4–32.1] 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). Lipid parameter No. (%) of patients with abnormal level Total cholesterol (≥200 mg/dL) 25 (62.5%) LDL (≥100 mg/dL) 34 (85%) HDL (female, <50 mg/dL) 16/30 (53.3%) HDL (male, 30 mg/dL, estimated) 11 (27.5%) Total cholesterol/HDL ratio > 5 16 (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). Parameter Preoperative Postoperative P-value HDL (mg/dL) 46.4 ± 6.6 46.2 ± 6.2 0.515 LDL (mg/dL) 128.7 ± 34.3 122.9 ± 31.6 0.002 Total cholesterol (mg/dL) 206.0 ± 37.1 194.8 ± 33.7 0.003 Triglycerides (mg/dL) 134 [106.75–162] 130.5 [107–164.25] 0.381 VLDL (mg/dL) 25.2 ± 7.7 23.6 ± 7.8 0.031 Total cholesterol/HDL ratio 4.60 ± 1.29 4.35 ± 1.17 0.004 AIP 0.45 ± 0.15 0.455 ± 0.15 0.216 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). Lipid parameter Preoperative, n (%) Postoperative, n (%) P-value High Total Cholesterol 25 (62.5%) 19 (47.5%) 0.07 High LDL 34 (85%) 34 (85%) 1.00 Low HDL 17 (42.5%) 17 (42.5%) 1.00 High Triglycerides 16 (40%) 15 (37.5%) 1.00 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 ×10 9 /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. Data availability Underlying data Zenodo: Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease. https://doi.org/10.5281/zenodo.17833365 . 16 This project contains the following extended data: • 5.12.2025.xlsx – Excel spreadsheet containing individual patient-level raw data for the study, including patient demographics (age, sex, weight, BMI, etc.), preoperative and 6-month postoperative lipid profile values for each patient (HDL, LDL, total cholesterol, triglycerides, VLDL), and calculated metrics (total cholesterol/HDL ratio and AIP) for all 40 patients. These extended data have been uploaded alongside the underlying data in the Zenodo repository. Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). References 1. Housset C, Chrétien Y, Debray D, et al. : Functions of the gallbladder. Compr. Physiol. 2016; 6 (3): 1549–1577. Publisher Full Text 2. Banim PJ, Luben RN, Bulluck H, et al. : The aetiology of symptomatic gallstone disease and the impact of cholecystectomy on cardiovascular disease risk. J. Public Health (Oxf.). 2011; 33 (4): 319–631. Publisher Full Text 3. Lamberts MP, Lugtenberg M, Rovers MM, et al. : Persistent abdominal symptoms after cholecystectomy: a systematic review. Am. J. Gastroenterol. 2013; 108 (2): 250–292. Publisher Full Text 4. Amigo L, Husche C, Zanlungo S, et al. : Cholecystectomy and bile acid synthesis: two sides of the same coin. J. Hepatol. 2011; 55 (3): 876–884. Publisher Full Text 5. Wang HH, Liu M, Wang ZL, et al. : The role of bile salt, phospholipids, and cholesterol in the process of gallstone formation. Dig. Dis. Sci. 2003; 48 (1): 89–94. Publisher Full Text 6. Portincasa P, Di Ciaula A, Wang HH, et al. : Coordinate regulation of gallbladder motor function in the gut-liver axis. Hepatology. 2008; 47 (6): 2112–2126. PubMed Abstract | Publisher Full Text 7. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002; 106 (25): 3143–3421. PubMed Abstract | Publisher Full Text 8. Dobiásová M, Frohlich J: The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER (HDL)). Clin. Biochem. 2001; 34 (7): 583–588. Publisher Full Text 9. Baigent C, Keech A, Kearney PM, et al. : Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005; 366 (9493): 1267–1278. PubMed Abstract | Publisher Full Text 10. Singh DK, Beera RC, Bodra P, et al. : Comparative study on effect of cholecystectomy on serum lipid profile in gallstone patients. Int. J. Acad. Med. Pharm. 2024; 6 : 445–451. 11. Reddy GP, Ramulakshmi Y, Antony AM, et al. : Role of Cholecystectomy on Serum Lipid Profile in Patients with Cholelithiasis. Cureus. 2022; 14 (10): e30624. PubMed Abstract | Publisher Full Text | Free Full Text 12. Farrugia A, Williams N, Kham S, et al. : Bile acid diarrhoea and metabolic therapies after cholecystectomy: a case-control study. ANZ J. Surg. 2024; 94 : 580–584. Publisher Full Text 13. Hofmann AF: The enterohepatic circulation of bile acids in health and disease. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 11th ed.Elsevier; 2020. chap 65. 14. Berr F, Stellaard F, Pratschke E, et al. : Effects of cholecystectomy on the kinetics of primary and secondary bile acids. J. Clin. Invest. 1989; 83 (5): 1541–1550. PubMed Abstract | Publisher Full Text | Free Full Text 15. Alatrash M, Saber M, Nashed GA, et al. : Impact of cholecystectomy on lipid profile levels postoperatively predicting its beneficial effect on dyslipidaemia [Preprint]. Research Square. 2025. Publisher Full Text 16. Alatrash M, Saber M, Nashed GA, et al. : Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease (Underlying dataset). [Data set]. Zenodo. 2025. Publisher Full Text Comments on this article Comments (1) Version 1 VERSION 1 PUBLISHED 30 Dec 2025 Reader Comment 10 Jan 2026 Massimo 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, Italy 10 Jan 2026 Reader Comment Dear 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 Dear 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 rather than a coordinated pulsatile release after meals, thus disrupting the normal accumulation of bile and controlled postprandial release. 13 (This change could alter the enterohepatic circulation of bile acids. Indeed, some studies have shown that bile acid synthesis increases after cholecystectomy. 14 Since bile acid synthesis consumes cholesterol, this could explain the reduction in total and LDL cholesterol observed in our study." 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. Dear 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 rather than a coordinated pulsatile release after meals, thus disrupting the normal accumulation of bile and controlled postprandial release. 13 (This change could alter the enterohepatic circulation of bile acids. Indeed, some studies have shown that bile acid synthesis increases after cholecystectomy. 14 Since bile acid synthesis consumes cholesterol, this could explain the reduction in total and LDL cholesterol observed in our study." 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. Competing Interests: Non-Financial Competing Interests Close Report a concern Comment ADD YOUR COMMENT Author details Author details 1 Cairo University Kasr Alainy Faculty of Medicine, Cairo, Cairo Governorate, Egypt Mohamed Alatrash Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Mohamed Saber Moustafa Roles: Data Curation, Formal Analysis, Investigation, Methodology, Resources, Supervision, Validation, Writing – Review & Editing George Abdelfady Nashed Roles: Conceptualization, Investigation, Methodology, Project Administration, Supervision, Writing – Review & Editing George Mosaad Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Project Administration, Visualization, Writing – Original Draft Preparation Mahmoud Dewair Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 30 Dec 2025, 14:1474 https://doi.org/10.12688/f1000research.174454.1 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. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE 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: 2 approved with reservations] . 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. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 30 Dec 2025 Views 0 Cite How to cite this report: Bamahry AR and Nurkolis F. Reviewer Report For: Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease: A Prospective, Single-Arm, Before-After Study [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :1474 ( https://doi.org/10.5256/f1000research.192358.r466414 ) The direct URL for this report is: https://f1000research.com/articles/14-1474/v1#referee-response-466414 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 06 Apr 2026 Aryanti R Bamahry , Universitas Muslim Indonesia, Makassar City, Indonesia Fahrul Nurkolis , Universitas Airlangga, Surabaya, Indonesia; Medical Research Center of Indonesia, Surabaya, 60281, Indonesia; Institute for Research and Community Service, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga),, Yogyakarta, 55281, Indonesia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.192358.r466414 First of all, this study addresses an interesting and clinically relevant question regarding the metabolic consequences of cholecystectomy, particularly its potential influence on lipid profiles. The manuscript is generally well-structured, and the authors present their findings in a clear and ... Continue reading READ ALL First of all, this study addresses an interesting and clinically relevant question regarding the metabolic consequences of cholecystectomy, particularly its potential influence on lipid profiles. The manuscript is generally well-structured, and the authors present their findings in a clear and concise manner. However, several important aspects need to be considered to strengthen the scientific rigor and interpretability of the results. One of the main concerns lies in the study design, which is a single-arm, before–after approach. While this design allows for preliminary observations, it inherently limits causal interpretation. Without a control group of patients with gallstone disease who did not undergo surgery, it is difficult to determine whether the observed changes in lipid profiles are truly attributable to cholecystectomy or simply reflect natural variation over time. Factors such as regression to the mean or perioperative physiological changes may have contributed to the modest improvements reported. Another critical limitation is the lack of control over confounding variables, particularly diet, physical activity, and weight changes. The manuscript mentions that patients were advised to maintain their usual lifestyle, but no objective data were collected to confirm adherence. This is important because postoperative dietary modification, especially reduced fat intake is very common after cholecystectomy and could independently explain the reduction in total cholesterol and LDL levels. Similarly, even small changes in body weight or BMI can significantly affect lipid metabolism, yet these variables were not reassessed at follow-up. In addition, although the study reports statistically significant reductions in total cholesterol and LDL, the clinical relevance of these changes appears limited. The decrease in LDL (~6 mg/dL) and total cholesterol (~11 mg/dL) is relatively small and unlikely to translate into meaningful cardiovascular risk reduction, especially when compared to established interventions such as statins or structured lifestyle modification. The manuscript does acknowledge this to some extent, but the discussion could be more cautious in framing these findings, emphasizing the absence of harm rather than suggesting a beneficial metabolic effect. The sample size (n=40) is another limitation. While acceptable for exploratory analysis, it reduces statistical power and generalizability. The absence of a priori sample size calculation further weakens the methodological robustness, even though this was transparently acknowledged by the authors. From a reporting perspective, the manuscript would benefit from additional clarity in the Methods section, particularly regarding: Whether any monitoring of dietary intake or physical activity was attempted Whether BMI or weight was reassessed postoperatively The exact formula used for calculating Atherogenic Index of Plasma (AIP) Moreover, the inclusion of visual data representation (e.g., paired plots showing individual patient changes) would significantly improve the interpretability of the results and help readers better appreciate the variability and magnitude of change across participants. Finally, while the discussion provides a reasonable mechanistic hypothesis involving bile acid metabolism, it remains largely speculative and not directly supported by measured biomarkers (e.g., bile acid levels or metabolic intermediates). Integrating more mechanistic or biochemical evidence would strengthen the translational value of the study. In summary, this study provides useful preliminary insights suggesting that cholecystectomy does not adversely affect lipid profiles and may be associated with modest improvements. However, due to methodological limitations particularly the lack of a control group and unmeasured confounders the findings should be interpreted with caution. Future studies with larger sample sizes, controlled designs, and more comprehensive metabolic profiling are needed to confirm these observations and clarify their clinical significance. Recommendations for Improvement Revise the title to make it more descriptive; avoid using the word “Impact” Include a more in-depth discussion of confounding factors Include (if available) data on changes in BMI and lifestyle Emphasize the difference between statistical and clinical significance Add a graph to clarify the data distribution Some references should be updated with recent studies that have had a significant impact Final Recommendations Major Revision Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Clinical Nutrition, Obesity and metabolic disease and Functional Food We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Bamahry AR and Nurkolis F. Reviewer Report For: Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease: A Prospective, Single-Arm, Before-After Study [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :1474 ( https://doi.org/10.5256/f1000research.192358.r466414 ) The direct URL for this report is: https://f1000research.com/articles/14-1474/v1#referee-response-466414 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Hu J. Reviewer Report For: Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease: A Prospective, Single-Arm, Before-After Study [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :1474 ( https://doi.org/10.5256/f1000research.192358.r460281 ) The direct URL for this report is: https://f1000research.com/articles/14-1474/v1#referee-response-460281 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 24 Feb 2026 Junqing Hu , The Third People’s Hospital of Chengdu, Chengdu, China Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.192358.r460281 This prospective study addresses a clinically relevant question regarding the metabolic consequences of cholecystectomy. The manuscript is concise, and the authors have collected valuable preliminary data. However, several significant methodological limitations, most of which the authors transparently acknowledge, prevent definitive ... Continue reading READ ALL This prospective study addresses a clinically relevant question regarding the metabolic consequences of cholecystectomy. The manuscript is concise, and the authors have collected valuable preliminary data. However, several significant methodological limitations, most of which the authors transparently acknowledge, prevent definitive conclusions and temper the clinical implications of the findings. The study would be strengthened by a more rigorous discussion of confounding variables and a more cautious interpretation of the results. Major Suggestions 1.The single-arm, before-after design is the primary limitation. As the authors correctly note in their discussion, the absence of a non-surgical control group with gallstone disease makes it impossible to attribute the observed lipid changes definitively to the cholecystectomy itself. The modest improvements observed could be explained by: -Regression to the mean: Lipid levels measured during a symptomatic period may have been temporarily elevated due to pain, stress, or altered dietary intake. -Post-operative lifestyle changes: Patients commonly modify their diet after surgery (e.g., reducing fat intake to avoid post-cholecystectomy symptoms), which could independently lower lipid levels. 2.The analysis does not account for factors that are known to significantly influence lipid profiles. -Diet and Lifestyle: As mentioned above, post-operative dietary changes are a major potential confounder. Did the authors collect any data on dietary habits before and after surgery? -Weight/BMI: Changes in weight can directly affect lipid levels. Was BMI or weight recorded at both time points? If patients lost weight post-operatively, this could explain the lipid changes. The authors' acknowledgment of these limitations in their discussion is commendable. However, to strengthen the manuscript, the Methods section should specify whether any attempt was made to collect these data, and the Results should include a table comparing potential confounders (e.g., medication use, BMI) between the two time points. 3.The authors appropriately note that the observed changes are "modest" and that cholecystectomy is "not a treatment for dyslipidemia." The approximately 6 mg/dL reduction in LDL-cholesterol, while statistically significant (p = 0.002), is clinically negligible for an individual patient and far smaller than what is achievable with lifestyle modification or low-dose statin therapy. The most clinically reassuring finding is the absence of a harmful effect on lipid profiles, and the manuscript should frame this as the primary takeaway rather than suggesting a "beneficial effect." Minor Suggestions 1.The title "Impact of Cholecystectomy on Lipid Profile Levels..." is strong and causal. Consider a more neutral title like: "Changes in Lipid Profile Six Months After Cholecystectomy for Gallstone Disease: A Prospective Before-After Study. " 2.Specify the formula used for AIP. 3.The results are presented clearly. A simple figure (e.g., a paired scatter plot or a bar chart with before/after values and lines connecting individual patients) would visually enhance the manuscript and show the distribution of changes. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Gallstone diseases. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Hu J. Reviewer Report For: Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease: A Prospective, Single-Arm, Before-After Study [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :1474 ( https://doi.org/10.5256/f1000research.192358.r460281 ) The direct URL for this report is: https://f1000research.com/articles/14-1474/v1#referee-response-460281 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (1) Version 1 VERSION 1 PUBLISHED 30 Dec 2025 Reader Comment 10 Jan 2026 Massimo 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, Italy 10 Jan 2026 Reader Comment Dear 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 Dear 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 rather than a coordinated pulsatile release after meals, thus disrupting the normal accumulation of bile and controlled postprandial release. 13 (This change could alter the enterohepatic circulation of bile acids. Indeed, some studies have shown that bile acid synthesis increases after cholecystectomy. 14 Since bile acid synthesis consumes cholesterol, this could explain the reduction in total and LDL cholesterol observed in our study." 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. Dear 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 rather than a coordinated pulsatile release after meals, thus disrupting the normal accumulation of bile and controlled postprandial release. 13 (This change could alter the enterohepatic circulation of bile acids. Indeed, some studies have shown that bile acid synthesis increases after cholecystectomy. 14 Since bile acid synthesis consumes cholesterol, this could explain the reduction in total and LDL cholesterol observed in our study." 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. Competing Interests: Non-Financial Competing Interests Close Report a concern Comment ADD YOUR COMMENT keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 30 Dec 25 read read Junqing Hu , The Third People’s Hospital of Chengdu, Chengdu, China Aryanti R Bamahry , Universitas Muslim Indonesia, Makassar City, Indonesia Fahrul Nurkolis , Universitas Airlangga, Surabaya, Indonesia; Medical Research Center of Indonesia, Surabaya, Indonesia; State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga),, Yogyakarta, Indonesia Comments on this article All Comments (1) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Bamahry A et al. This is an open access peer review report 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. 06 Apr 2026 | for Version 1 Aryanti R Bamahry , Universitas Muslim Indonesia, Makassar City, Indonesia Fahrul Nurkolis , Universitas Airlangga, Surabaya, Indonesia; Medical Research Center of Indonesia, Surabaya, 60281, Indonesia; Institute for Research and Community Service, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga),, Yogyakarta, 55281, Indonesia 0 Views copyright © 2026 Bamahry A et al. This is an open access peer review report 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. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions First of all, this study addresses an interesting and clinically relevant question regarding the metabolic consequences of cholecystectomy, particularly its potential influence on lipid profiles. The manuscript is generally well-structured, and the authors present their findings in a clear and concise manner. However, several important aspects need to be considered to strengthen the scientific rigor and interpretability of the results. One of the main concerns lies in the study design, which is a single-arm, before–after approach. While this design allows for preliminary observations, it inherently limits causal interpretation. Without a control group of patients with gallstone disease who did not undergo surgery, it is difficult to determine whether the observed changes in lipid profiles are truly attributable to cholecystectomy or simply reflect natural variation over time. Factors such as regression to the mean or perioperative physiological changes may have contributed to the modest improvements reported. Another critical limitation is the lack of control over confounding variables, particularly diet, physical activity, and weight changes. The manuscript mentions that patients were advised to maintain their usual lifestyle, but no objective data were collected to confirm adherence. This is important because postoperative dietary modification, especially reduced fat intake is very common after cholecystectomy and could independently explain the reduction in total cholesterol and LDL levels. Similarly, even small changes in body weight or BMI can significantly affect lipid metabolism, yet these variables were not reassessed at follow-up. In addition, although the study reports statistically significant reductions in total cholesterol and LDL, the clinical relevance of these changes appears limited. The decrease in LDL (~6 mg/dL) and total cholesterol (~11 mg/dL) is relatively small and unlikely to translate into meaningful cardiovascular risk reduction, especially when compared to established interventions such as statins or structured lifestyle modification. The manuscript does acknowledge this to some extent, but the discussion could be more cautious in framing these findings, emphasizing the absence of harm rather than suggesting a beneficial metabolic effect. The sample size (n=40) is another limitation. While acceptable for exploratory analysis, it reduces statistical power and generalizability. The absence of a priori sample size calculation further weakens the methodological robustness, even though this was transparently acknowledged by the authors. From a reporting perspective, the manuscript would benefit from additional clarity in the Methods section, particularly regarding: Whether any monitoring of dietary intake or physical activity was attempted Whether BMI or weight was reassessed postoperatively The exact formula used for calculating Atherogenic Index of Plasma (AIP) Moreover, the inclusion of visual data representation (e.g., paired plots showing individual patient changes) would significantly improve the interpretability of the results and help readers better appreciate the variability and magnitude of change across participants. Finally, while the discussion provides a reasonable mechanistic hypothesis involving bile acid metabolism, it remains largely speculative and not directly supported by measured biomarkers (e.g., bile acid levels or metabolic intermediates). Integrating more mechanistic or biochemical evidence would strengthen the translational value of the study. In summary, this study provides useful preliminary insights suggesting that cholecystectomy does not adversely affect lipid profiles and may be associated with modest improvements. However, due to methodological limitations particularly the lack of a control group and unmeasured confounders the findings should be interpreted with caution. Future studies with larger sample sizes, controlled designs, and more comprehensive metabolic profiling are needed to confirm these observations and clarify their clinical significance. Recommendations for Improvement Revise the title to make it more descriptive; avoid using the word “Impact” Include a more in-depth discussion of confounding factors Include (if available) data on changes in BMI and lifestyle Emphasize the difference between statistical and clinical significance Add a graph to clarify the data distribution Some references should be updated with recent studies that have had a significant impact Final Recommendations Major Revision Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Clinical Nutrition, Obesity and metabolic disease and Functional Food We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. reply Respond to this report Responses (0) Bamahry AR and Nurkolis F. Peer Review Report For: Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease: A Prospective, Single-Arm, Before-After Study [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :1474 ( https://doi.org/10.5256/f1000research.192358.r466414) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1474/v1#referee-response-466414 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Hu J. This is an open access peer review report 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. 24 Feb 2026 | for Version 1 Junqing Hu , The Third People’s Hospital of Chengdu, Chengdu, China 0 Views copyright © 2026 Hu J. This is an open access peer review report 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. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This prospective study addresses a clinically relevant question regarding the metabolic consequences of cholecystectomy. The manuscript is concise, and the authors have collected valuable preliminary data. However, several significant methodological limitations, most of which the authors transparently acknowledge, prevent definitive conclusions and temper the clinical implications of the findings. The study would be strengthened by a more rigorous discussion of confounding variables and a more cautious interpretation of the results. Major Suggestions 1.The single-arm, before-after design is the primary limitation. As the authors correctly note in their discussion, the absence of a non-surgical control group with gallstone disease makes it impossible to attribute the observed lipid changes definitively to the cholecystectomy itself. The modest improvements observed could be explained by: -Regression to the mean: Lipid levels measured during a symptomatic period may have been temporarily elevated due to pain, stress, or altered dietary intake. -Post-operative lifestyle changes: Patients commonly modify their diet after surgery (e.g., reducing fat intake to avoid post-cholecystectomy symptoms), which could independently lower lipid levels. 2.The analysis does not account for factors that are known to significantly influence lipid profiles. -Diet and Lifestyle: As mentioned above, post-operative dietary changes are a major potential confounder. Did the authors collect any data on dietary habits before and after surgery? -Weight/BMI: Changes in weight can directly affect lipid levels. Was BMI or weight recorded at both time points? If patients lost weight post-operatively, this could explain the lipid changes. The authors' acknowledgment of these limitations in their discussion is commendable. However, to strengthen the manuscript, the Methods section should specify whether any attempt was made to collect these data, and the Results should include a table comparing potential confounders (e.g., medication use, BMI) between the two time points. 3.The authors appropriately note that the observed changes are "modest" and that cholecystectomy is "not a treatment for dyslipidemia." The approximately 6 mg/dL reduction in LDL-cholesterol, while statistically significant (p = 0.002), is clinically negligible for an individual patient and far smaller than what is achievable with lifestyle modification or low-dose statin therapy. The most clinically reassuring finding is the absence of a harmful effect on lipid profiles, and the manuscript should frame this as the primary takeaway rather than suggesting a "beneficial effect." Minor Suggestions 1.The title "Impact of Cholecystectomy on Lipid Profile Levels..." is strong and causal. Consider a more neutral title like: "Changes in Lipid Profile Six Months After Cholecystectomy for Gallstone Disease: A Prospective Before-After Study. " 2.Specify the formula used for AIP. 3.The results are presented clearly. A simple figure (e.g., a paired scatter plot or a bar chart with before/after values and lines connecting individual patients) would visually enhance the manuscript and show the distribution of changes. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Gallstone diseases. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Hu J. Peer Review Report For: Impact of Cholecystectomy on Lipid Profile Levels in Patients With Gallstone Disease: A Prospective, Single-Arm, Before-After Study [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :1474 ( https://doi.org/10.5256/f1000research.192358.r460281) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1474/v1#referee-response-460281 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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