Gallstone disease is a prevalent condition worldwide, frequently necessitating surgical intervention, with laparoscopic cholecystectomy now considered the gold standard for symptomatic cholelithiasis【1】. This minimally invasive procedure offers clear advantages over open cholecystectomy, including reduced postoperative pain, shorter hospital stays, and faster recovery times【2】. Since its introduction, laparoscopic cholecystectomy has transformed biliary surgery and is now among the most commonly performed abdominal operations【3】.

Despite its widespread adoption and safety profile, laparoscopic cholecystectomy is not without challenges. Intraoperative factors, such as severe inflammation, adhesions, or anatomical variations, can increase the difficulty of the procedure and the risk of complications【4】. A crucial aspect of the operation is the creation of a pneumoperitoneum using carbon dioxide, which provides the necessary workspace for visualization and manipulation of the gallbladder and biliary tree【5】.

However, carbon dioxide pneumoperitoneum can influence various physiological parameters, including splanchnic and hepatic blood flow, potentially leading to transient alterations in liver function tests (LFTs)【6】. Although most changes in liver enzymes after laparoscopic cholecystectomy are clinically insignificant and self-limited, there is ongoing interest in understanding the relationship between the duration of pneumoperitoneum and the extent of hepatic biochemical disturbances【7】.

Given the high prevalence of gallstone disease and the increasing use of laparoscopic techniques, further investigation into the perioperative hepatic effects of carbon dioxide insufflation is warranted. The present study aims to evaluate the serial changes in serum liver enzymes and bilirubin following laparoscopic cholecystectomy and to assess the impact of pneumoperitoneum duration on these parameters in a tertiary care setting.

Aims and Objectives

The primary aim of this study was to evaluate the effect of carbon dioxide pneumoperitoneum on liver function tests in patients undergoing laparoscopic cholecystectomy. Specifically, the objectives were:

1. To assess the incidence and magnitude of alterations in serum ALT, AST, ALP, and total bilirubin following laparoscopic cholecystectomy.
2. To determine whether the duration of pneumoperitoneum (>60 minutes vs. ≤60 minutes) significantly influences these biochemical changes.
3. To evaluate the clinical significance and reversibility of postoperative liver enzyme elevations in this patient population.

Study Design and Setting

This prospective, observational study was conducted at North 24 Parganas District Hospital, Barasat, Kolkata, between March 2017 and September 2018. The study protocol was approved by the institutional ethics committee, and written informed consent was obtained from all participants.

Study Population

A total of 170 consecutive patients scheduled for elective laparoscopic cholecystectomy were included. Inclusion criteria were age between 24 and 60 years, clinical diagnosis of symptomatic cholelithiasis, and normal preoperative liver function tests. Exclusion criteria comprised abnormal baseline liver enzymes, evidence of chronic liver disease, common bile duct pathology, conversion to open surgery, intraoperative complications, and incomplete data.

Group Allocation

Patients were stratified into two groups based on the duration of carbon dioxide pneumoperitoneum during surgery:

• Group L (≤60 minutes): 110 patients
• Group M (>60 minutes): 60 patients

Duration of pneumoperitoneum was defined as the time from insufflation to deflation of carbon dioxide.

Surgical Procedure

All surgeries were performed under general anesthesia using a standard four-port laparoscopic technique. Pneumoperitoneum was created and maintained with carbon dioxide at an intra-abdominal pressure of 12 mmHg throughout the procedure.

Data Collection

Venous blood samples were collected for liver function tests—serum ALT (alanine aminotransferase), AST (aspartate aminotransferase), ALP (alkaline phosphatase), and total bilirubin—at the following time points:

• Preoperatively (within 24 hours before surgery)
• Postoperative day 1
• Postoperative day 3
• Postoperative day 7

All samples were processed in the hospital laboratory on the same day of collection. Clinical and perioperative data, including demographic information, duration of surgery, intraoperative and postoperative complications, and length of hospital stay, were also recorded.

Data were entered into Microsoft Excel and analyzed using SPSS version 24.0 and GraphPad Prism 5.0. Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables as counts and percentages. Comparisons between groups were performed using the unpaired t-test for continuous variables and the chi-square test for categorical variables. Paired t-tests were used to compare serial enzyme measurements within groups. A p-value <0.05 was considered statistically significant.

1. Patient Demographics and Baseline Characteristics

A total of 170 patients undergoing elective laparoscopic cholecystectomy were included in the study. The cohort comprised 130 females (76.5%) and 40 males (23.5%), with a mean age of 39.8 ± 7.1 years (range: 24–60 years). The majority of patients (approximately 58%) were in the 30–40-year age group.

Patients were stratified based on the duration of pneumoperitoneum into two groups:

• Group L (≤60 minutes): 110 patients (64.7%)
• Group M (>60 minutes): 60 patients (35.3%)

There were no statistically significant differences between the two groups with respect to age, gender distribution, or baseline (preoperative) liver function test values (ALT, AST, ALP, total bilirubin) (all p > 0.05).

Table 1. Patient Demographics and Baseline Liver Function Tests

*Gender comparison by chi-square test; other variables by unpaired t-test. Values are mean ± SD unless otherwise stated.

2. Perioperative Outcomes

The duration of surgery was ≤60 minutes in 64.7% of cases and >60 minutes in 35.3%. No major intraoperative or postoperative complications occurred in either group. The mean postoperative hospital stay was 3.5 ± 0.8 days (range, 2–5 days), with most patients (95%) discharged by postoperative day 4. Early postoperative recovery was comparable between groups, with no instances of delayed recovery or hospital readmission (Table 2).

Table 2. Perioperative Outcomes

                        Values are mean ± SD or n (%), as indicated.

3. Liver Function Tests: Trends and Comparisons

Serial measurements of liver function tests (ALT/SGPT, AST/SGOT, ALP, and total bilirubin) were obtained preoperatively and on postoperative days 1, 3, and 7 in both groups. Preoperative enzyme levels were comparable between the ≤60 min and >60 min groups (p > 0.05 for all comparisons).

Following surgery, both groups demonstrated significant transient elevations in all measured liver enzymes and bilirubin on postoperative day 1. These increases were more pronounced in patients with pneumoperitoneum duration >60 minutes (p < 0.001 for all enzymes). Enzyme levels declined rapidly by postoperative day 3 and returned to near preoperative values by day 7 in both groups.

Table 3. Serial Changes in Liver Function Tests Pre- and Post-operatively by Group

Values are mean ± SD; p-values from unpaired t-tests comparing ≤60 min and >60 min groups at each time point.

On postoperative day 1, all liver function parameters were significantly higher in the >60 min group compared to the ≤60 min group (p < 0.001 for all enzymes). By day 3, enzyme levels decreased substantially and were not significantly different between the groups. By day 7, all parameters had normalized to near preoperative levels in both groups.

4. Clinical Outcomes and Adverse Events

No patients in either group developed clinical hepatic dysfunction following laparoscopic cholecystectomy. There were no intraoperative or postoperative complications, including bile duct injury, haemorrhage, surgical site infection, or other significant adverse events. No conversions to open surgery were required.

All patients experienced an uneventful postoperative course, with no readmissions or delayed recovery during the study period. The transient elevation in liver enzyme levels observed postoperatively had no clinical consequences, and all patients were discharged in stable condition within five days of surgery.

In summary, laparoscopic cholecystectomy in this cohort resulted in a significant but transient increase in serum liver enzyme levels and total bilirubin, with greater elevations observed in patients undergoing longer durations of pneumoperitoneum (>60 minutes). All laboratory parameters returned to near baseline values within one week postoperatively, and no adverse clinical outcomes or complications were observed in any patient.

This prospective observational study evaluated serial changes in liver function tests following laparoscopic cholecystectomy and assessed the impact of pneumoperitoneum duration on postoperative hepatic enzyme alterations. Our findings indicate a significant but transient elevation in ALT, AST, ALP, and total bilirubin levels on postoperative day 1, particularly in patients who underwent prolonged pneumoperitoneum (>60 minutes). All values returned to near baseline by day 7, and no patients exhibited clinical hepatic dysfunction or complications.

The observed transient elevation in liver enzymes aligns with the physiological effects of carbon dioxide insufflation during laparoscopic surgery. As demonstrated by Ibraheim et al., carbon dioxide pneumoperitoneum can result in metabolic and acid-base changes due to its effect on splanchnic circulation, contributing to temporary hepatocellular stress and altered enzyme levels【8】. In our study, ALT increased from a preoperative mean of 23.7 ± 7.9 U/L (≤60 min group) and 23.2 ± 7.7 U/L (>60 min group) to 38.5 ± 13.1 U/L and 46.4 ± 12.6 U/L, respectively, on postoperative day 1—a rise of over 60% in the ≤60 min group and nearly 100% in the >60 min group. Similar patterns were observed for AST, ALP, and total bilirubin.

Statistically, the postoperative day 1 differences in enzyme elevations between groups were highly significant (p < 0.001 for all parameters), supporting a clear association between longer pneumoperitoneum duration and greater hepatic biochemical disturbance. Schwenk et al. and Junghans et al. have similarly reported that increased intra-abdominal pressure and duration of insufflation can exacerbate hemodynamic alterations, potentially amplifying hepatic enzyme release【9】【10】.

Despite these statistically significant changes, the absence of clinical complications in our cohort is notable. No patient developed symptoms or signs of hepatic dysfunction, and all were discharged within five days postoperatively. This finding is consistent with Gutt et al., who concluded that while circulatory and respiratory complications are possible with CO₂ insufflation, significant liver dysfunction is rare when proper patient selection is observed【11】.

Our results are in agreement with Saber et al., who observed that elevations in liver function tests following laparoscopic cholecystectomy are relatively common but seldom lead to adverse clinical outcomes【12】. In our cohort, enzyme levels approached preoperative values by day 3 and normalized by day 7, mirroring the recovery trajectory described in their series. The mean difference in ALT and AST between groups on day 1 (ALT: 7.94 U/L higher in >60 min; AST: 12.78 U/L higher in >60 min) further supports the role of pneumoperitoneum duration as a contributing factor.

Several previous studies reinforce our findings regarding the transient nature and limited clinical significance of enzyme elevations. Sakorafas et al. documented similar transient rises in AST and ALT postoperatively, with normalization by day 10【13】. Morino et al. and Hasukic et al. both observed that higher insufflation pressures and longer operative times correlated with greater, though self-limited, increases in hepatic enzymes【14】【15】. Our results, showing normalization of LFTs by day 7 and lack of adverse events, are consistent with these benchmarks.

Potential mechanisms for enzyme elevation include reduced portal venous flow, direct pressure effects on the liver, and neurohumoral responses to intra-abdominal hypertension. Bryant et al. and Luk et al. have highlighted that such physiological perturbations, including inflammatory mediator release (e.g., interleukin-6), may transiently affect hepatic integrity without causing lasting dysfunction【16】【17】.

A key strength of our study is the robust sample size and consistent follow-up, allowing for reliable detection of transient biochemical changes. However, it is important to note that all patients had normal preoperative liver function, and results may not generalize to those with pre-existing hepatic impairment. Additionally, our study did not include a comparison with open cholecystectomy or alternative pneumoperitoneum pressures.

In summary, our findings corroborate existing evidence that carbon dioxide pneumoperitoneum during laparoscopic cholecystectomy induces a predictable, transient rise in serum liver enzymes, with the extent of elevation strongly associated with the duration of insufflation. These changes are of statistical but not clinical significance in patients without baseline hepatic dysfunction, supporting the overall safety of the procedure within standard operative parameters.

Limitations

This study was limited by its observational design and inclusion of only patients with normal preoperative liver function; thus, results may not be generalizable to those with pre-existing hepatic impairment. Additionally, no comparison was made with open cholecystectomy or varying insufflation pressures.

Laparoscopic cholecystectomy is associated with a significant but transient elevation in liver enzymes and total bilirubin, particularly in patients undergoing prolonged carbon dioxide pneumoperitoneum. These biochemical changes are not accompanied by clinical hepatic dysfunction and normalize within one week postoperatively. The procedure remains safe and well-tolerated in patients with normal baseline liver function.

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