Changes in Lipid Profile Six Months After Cholecystectomy for Gallstone Disease: A Prospective Before-After Study

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 describe changes in lipid profiles by comparing preoperative measurements with those obtained at a 6-month postoperative follow-up. As symptomatic gallstone disease is itself an indication for surgery, an observational control group of unoperated symptomatic patients was not pursued for ethical reasons; the implications of this design choice are addressed in the Discussion.

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.

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. The preoperative blood draw was performed during a routine outpatient visit and not during an acute biliary episode.

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 stabilisation 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 verbally counselled to maintain their usual diet and lifestyle during the follow-up period, and none initiated lipid-lowering therapy. Dietary intake and physical activity were not formally captured by food-frequency questionnaire or activity diary, and weight and BMI were not re-measured at the 6-month visit; these omissions are addressed as limitations in the Discussion.

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 The Atherogenic Index of Plasma was calculated according to Dobiášová and Frohlich⁸ as:

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 summarised 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 a prior sample size calculation was performed; this is acknowledged as a limitation, and the present study should be regarded as exploratory.

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.

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%).

Changes in lipid profile postoperatively

As summarised in Table 4, cholecystectomy was associated with statistically significant but small improvements in several 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 small but significant reduction (25.2 ± 7.7 to 23.6 ± 7.8 mg/dL; p = 0.031). The total cholesterol/HDL ratio decreased significantly from 4.60 ± 1.29 to 4.35 ± 1.17 (p = 0.004). The clinical relevance of these statistical changes is discussed below.

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 small statistically significant improvements in mean lipid levels, the proportion of patients classified as having dyslipidemia did not change substantively after surgery. As shown in Table 5, the percentage of patients with high total cholesterol fell 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) was unchanged. There was also a non-significant decrease in the proportion of patients with high triglycerides (40% vs. 37.5%; p = 1.00). No patient who was significantly dyslipidemic preoperatively achieved a complete normalisation of their lipid profile on the basis of surgery alone.

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.

Magnitude of change in clinical context

The magnitude of the observed lipid changes is small in clinical terms. The approximately 6 mg/dL reduction in mean LDL cholesterol and the approximately 11 mg/dL reduction in mean total cholesterol, while statistically significant, are at least an order of magnitude smaller than the changes typically achieved with established interventions: low- to moderate-intensity statin therapy lowers LDL by 30–50% (often 40–70 mg/dL in absolute terms) and produces a corresponding reduction in major cardiovascular events,⁹ while structured lifestyle modification including dietary change, exercise, and weight loss can lower LDL by 10–20%. The changes observed in our cohort are therefore unlikely to translate into a meaningful reduction in individual cardiovascular risk and should not be presented as a treatment effect.

Previous studies examining post-cholecystectomy lipid changes have reported heterogeneous results. Singh et al. (2024) reported significant decreases in total cholesterol, LDL, and triglycerides and an increase in HDL at 1 month after cholecystectomy in a cohort of 72 patients,¹⁰ and Reddy et al. (2022) observed similar reductions in total cholesterol, LDL, triglycerides, and VLDL with a small increase in HDL.¹¹ The directional changes for LDL and total cholesterol in our cohort are broadly consistent with these reports, although our study did not show changes in HDL or triglycerides; this may reflect differences in baseline characteristics, follow-up interval, or sample size. In contrast, Farrugia et al. (2024), in a case-control study with a 1-year follow-up, found no significant differences in lipid profiles after cholecystectomy and reported a significant increase in triglycerides.¹² The case-control design of that study provides a more robust framework for causal inference than the present work and underscores the importance of confirming our observations in controlled cohorts.

Possible mechanisms

The mechanisms by which cholecystectomy might influence lipid metabolism remain incompletely understood, and any mechanistic interpretation of our findings is necessarily speculative as we did not measure bile-acid kinetics or related biomarkers. One frequently proposed mechanism is that, in the absence of a gallbladder reservoir, bile flows continuously into the small intestine rather than in coordinated postprandial pulses, increasing the frequency of enterohepatic circulation of bile acids.¹³ Increased bile-acid synthesis after cholecystectomy has been demonstrated in earlier kinetic studies,¹⁴ and because bile-acid synthesis consumes hepatic cholesterol, this could in principle account for a modest reduction in total and LDL cholesterol. However, this hypothesis was not directly tested in the present study, and future work incorporating measurement of circulating or faecal bile acids, FGF19, or 7α-hydroxy-4-cholesten-3-one (C4) would help clarify the underlying mechanisms.

From a clinical perspective, our findings do not support the use of cholecystectomy as a treatment for dyslipidemia. The improvements in LDL and total cholesterol, while statistically significant, are too small to be clinically meaningful in isolation, and the proportion of patients meeting criteria for dyslipidemia did not change. The most clinically relevant message for practice is therefore reassurance — that, on average, removal of the gallbladder for symptomatic gallstone disease does not appear to worsen the lipid profile in the short to intermediate term. This is potentially a useful counselling point for patients who ask whether cholecystectomy will adversely affect their cholesterol or weight.

An earlier version of this work was posted online as a preprint.¹⁵

Limitations

This study has several important limitations that constrain the interpretation of our results.

First, the single-arm before-after design does not allow causal attribution of the observed lipid changes to cholecystectomy itself. Without a non-surgical control group of patients with symptomatic gallstone disease followed for the same period, we cannot exclude regression to the mean, the natural history of the underlying disease, secular trends, or perioperative physiological changes as alternative explanations. An observational control group of unoperated symptomatic patients was not pursued for ethical reasons, as symptomatic cholelithiasis is itself an indication for surgery; we recognise, however, that this is a major methodological limitation.

Second, we did not formally measure several variables that are known to influence lipid metabolism. Dietary intake and physical activity were not captured by food-frequency questionnaire or activity diary; patients were verbally counselled to maintain habitual diet and lifestyle, but adherence was not objectively verified. We acknowledge that postoperative dietary modification, particularly transient avoidance of fatty foods, is common in the early period following cholecystectomy. In our clinical experience this dietary adjustment is typically limited to the first 7–10 postoperative days, after which patients return to habitual intake; however, we cannot exclude a sustained dietary effect contributing to the observed lipid changes. Similarly, body weight and BMI were recorded at baseline only and were not re-measured at the 6-month follow-up, so even small weight changes could have contributed to the observed differences.

Third, the magnitude of the observed changes was small, and the proportion of patients with dyslipidemia did not change substantively. Statistically significant differences should therefore not be interpreted as clinically meaningful effects.

Fourth, the sample size of 40 patients is small. No formal a prior sample size calculation was performed, and the study should be regarded as exploratory and hypothesis-generating. The limited power may have prevented detection of true changes in HDL, triglycerides, and AIP.

Fifth, the 6-month follow-up captures only intermediate-term changes; longer-term effects on lipid metabolism cannot be inferred from these data.

Sixth, no biomarkers of bile-acid metabolism (e.g., serum or faecal bile acids, FGF19, or C4) were measured, so the mechanistic discussion above remains speculative.

These limitations should be borne in mind when interpreting the findings, and they highlight the need for larger, controlled studies with longer follow-up, comprehensive lifestyle data, and direct mechanistic measurements to clarify the metabolic consequences of cholecystectomy.