Modeling Post-cholecystitis Complication Risk from Perioperative Liver Function and Immune-inflammation Indicators
Abstract
Acute calculous cholecystitis (ACC) often triggers transient perioperative elevations in liver enzymes and systemic inflammation, yet existing complication-prediction tools seldom incorporate dynamic biomarker changes. Our goal was to establish and develop, using internal validation, a multivariable risk model that incorporates perioperative variations in liver function tests (LFTs) and the Systemic Immune-Inflammation Index (SII) in order to predict Clavien–Dindo grade ≥II complications following cholecystectomy for ACC. In this retrospective cohort study at a tertiary academic center (January 2022–December 2024), we analyzed 260 adult patients undergoing laparoscopic or open cholecystectomy for ACC.
We calculated Δ-values (day 1 minus baseline) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and SII (platelet × neutrophil/lymphocyte). Multivariable logistic regression with backward stepwise selection was used to derive the final model, which included ΔALT, ΔAST, Δbilirubin, ΔSII, age, American Society of Anesthesiologists (ASA) status, and operative duration. Internal validation employed 1 000 bootstrap replications.
The model demonstrated good discrimination (optimism-corrected area under the curve, 0.82; 95% CI, 0.77–0.87) and excellent calibration (slope, 0.95; intercept, –0.02). Significant predictors included ΔALT, ΔAST, Δbilirubin, and ΔSII, along with age, ASA III status, and longer operative duration. The decision-curve analysis demonstrated net benefit across threshold probabilities of 5% to 40%, with 15 additional true positives per 1 000 at the 20% threshold.
Integrating dynamic perioperative changes in LFTs and SII with key clinical factors yields a robust risk prediction model for postoperative complications after ACC surgery.
1. Ambe PC, Weber SA, Zirngibl H. Acute calculous cholecystitis: review of current best practices. World J Emerg Surg. 2017;12(4):23.
2. Strasberg SM. Clinical practice. Acute calculous cholecystitis. N Engl J Med. 2008;358(26):2804-11.
3. Sakorafas GH, Tsiotou AG, Farley DR, et al. Changes in liver function tests after laparoscopic cholecystectomy. Br J Surg. 1999;86(8):960-3.
4. Choudhury U, Dutta PS. Alterations in liver enzymes in the postoperative period following laparoscopic and open cholecystectomy. J Clin Diagn Res. 2023;17(6):PC14-PC17.
5. Hu B, Yang XR, Xu Y, et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20(23):6212-22.
6. Li MJ, Zhao TX, Wang J, et al. Role of systemic immune-inflammation index in predicting postoperative complications in colorectal cancer. World J Clin Cases. 2022;10(15):4810-18.
7. Collins GS, Reitsma JB, Altman DG, Moons KG. Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD): the TRIPOD statement. BMJ. 2015;350:g7594.
8. Jean-Antony S. Acute Cholecystitis: The Evaluation of Treatment Outcomes and Prognostic Factors. Master's thesis, Lithuanian University of Health Sciences (Lithuania); 2022.
9. Deleu S, Arnauts K, Machiels K, Huys G, Thevelein J, Raes J, Vermeire S. High acetate concentration reduces inflammation in organoid-derived epithelial monolayer from patients with ulcerative colitis (or UC patients). Acta Gastro-Enterologica Belgica. 2022;85(1):Fasc.
10. Ahmed M, Abdallah SA. Effect of different levels of intraperitoneal pneumoperitoneum on liver enzymes during laparoscopic cholecystectomy. Med J Cairo Univ. 2022;90(3):547-56.
11. Salati SA. Liver enzyme alterations after laparoscopic cholecystectomy (LC)–a study. J Health Sci Res. 2022;7(2):24-7.
12. He K, Si L, Pan X, Sun L, Wang Y, Lu J, Wang X. Preoperative systemic immune–inflammation index (SII) as a superior predictor of long-term survival outcome in patients with stage I–II gastric cancer after radical surgery. Front Oncol. 2022;12:829689.
13. Tudor MS, Gheorman V, Simeanu GM, Dobrinescu A, Pădureanu V, Dinescu VC, Forțofoiu MC. Evolutive models, algorithms and predictive parameters for the progression of hepatic steatosis. Metabolites. 2024;14(4):198.
14. Trebicka J, Hernaez R, Shawcross DL, Gerbes AL. Recent advances in the prevention and treatment of decompensated cirrhosis and acute-on-chronic liver failure (ACLF) and the role of biomarkers. Gut. 2024;73(6):1015-24.
15. Nair RT, Chan A, Morgan MA, Itani M, Ganeshan D, Arif-Tiwari H, El-Haddad E, Sabujan A, Dawkins AA. Biliary complications of surgical procedures: what the radiologist needs to know. Abdom Radiol. 2024:1-21.
16. Giakoustidis A, Papakonstantinou M, Gkoutzios C, Chatzikomnitsa P, Gkaitatzi AD, Myriskou A, Bangeas P, Loufopoulos PD, Papadopoulos VN, Giakoustidis D. Transient elevation of liver function tests and bilirubin levels after laparoscopic cholecystectomy. Medicina. 2024;60(11):1885.
17. Mannam R, Narayanan RS, Bansal A, Yanamaladoddi VR, Sarvepalli SS, Vemula SL, Aramadaka S. Laparoscopic cholecystectomy versus open cholecystectomy in acute cholecystitis: a literature review. Cureus. 2023;15(9).
18. Liu CQ, Yu ZB, Gan JX, Mei TM. Preoperative blood markers and intra-abdominal infection after colorectal cancer resection. World J Gastrointest Surg. 2024;16(2):451.
19. Shevchenko I, Grigorescu CC, Serban D, Cristea BM, Simion L, Gherghiceanu F, Costea AC, Dumitrescu D, Alius C, Tudor C, Onisai M. The value of systemic inflammatory indices for predicting early postoperative complications in colorectal cancer. Medicina. 2024;60(9):1481.
20. Jiao Y, Zhang X, Liu M, Sun YE, Ma Z, Gu X, Gu W, Zhu W. Systemic immune-inflammation index within the first postoperative hour as a predictor of severe postoperative complications in upper abdominal surgery: a retrospective single-center study. BMC Gastroenterol. 2022;22(1):403.
21. Gu P, Xu P, Chen Y, Li J, Sun H, Xu H, Lu Q. The predictive value of pan-immune inflammatory index for early recurrence of atrial fibrillation after cryoablation. BMC Cardiovasc Disord. 2024;24(1):669.
22. Tejeda-Herrera D, Caballero-Alvarado J, Zavaleta-Corvera C. The American College of Surgeons-National Surgical Quality Improvement Program calculator and surgical apgar as predictors of post-cholecystectomy complications. ABCD Arq Bras Cir Dig. 2024;37:e1862.
23. Spota A, Hassanpour A, Shlomovitz E, Gomez D, Al-Sukhni E. Acute cholecystitis management at a tertiary care center: are we following current guidelines? Langenbecks Arch Surg. 2024;409(1):323.
24. Rasslan R, Dos Santos JP, Menegozzo CA, Pezzano AV, Lunardeli HS, dos Santos Miranda J, Utiyama EM, Damous SH. Outcomes after emergency abdominal surgery in COVID-19 patients at a referral center in Brazil. Updates Surg. 2021;73(4):763-8.
25. Leiby J. Advancement and Application of Deep Learning Techniques for Biomedical Image Analysis: Diagnostics, Risk, and Biomarker Prediction. Doctoral dissertation, University of Pennsylvania; 2023.
26. Zhang X, Yue P, Zhang J, Yang M, Chen J, Zhang B, Luo W, Wang M, Da Z, Lin Y, Zhou W. A novel machine learning model and a public online prediction platform for prediction of post-ERCP-cholecystitis (PEC). EClinicalMedicine. 2022;48.
27. Wasilewski T, Kamysz W, Gębicki J. AI-assisted detection of biomarkers by sensors and biosensors for early diagnosis and monitoring. Biosensors. 2024;14(7):356.
28. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453-7.
29. Hong YM, Yoon KT, Cho M. Systemic immune-inflammation index predicts prognosis of sequential therapy with sorafenib and regorafenib in hepatocellular carcinoma. BMC Cancer. 2021;21:569. doi:10.1186/s12885-021-08124-9.
30. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205-13.
31. Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49(12):1373-9.
32. Jomrich G, Gruber ES, Winkler D, et al. Systemic immune-inflammation index (SII) predicts poor survival in pancreatic cancer patients undergoing resection. J Gastrointest Surg. 2020;24:610–618. doi:10.1007/s11605-019-04187-z.
33. Hasukic S, Kosuta D, Muminhodzic K. Comparison of postoperative hepatic function between laparoscopic and open cholecystectomy. Med Princ Pract. 2005;14(3):147-50.
34. Guven HE, Oral S. Liver enzyme alterations after laparoscopic cholecystectomy. J Gastrointestin Liver Dis. 2007;16(4):391-4.
35. Morino M, Giraudo G, Festa V. Alterations in hepatic function during laparoscopic surgery: an experimental clinical study. Surg Endosc. 1998;12(7):968-72.
36. Varma KR, Rabindranath RM, Bibekananda BD, Patra KK. Transient Alterations in Liver Enzymes Following Laparoscopic Cholecystectomy: Impact of Carbon Dioxide Pneumoperitoneum Duration in a Prospective Cohort. Journal of Contemporary Clinical Practice. 2025 Aug;11(8):266-272. .
37. Qi Q, Zhuang L, Shen Y, et al. A novel systemic immune-inflammation index predicts prognosis in patients after curative resection for gastric cancer. Clin Cancer Res. 2017;23(17):5504-12.
38. Jiang N, Deng JY, Liu Y. Systemic immune-inflammation index as a prognostic marker in colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis. 2021;36(5):1037-45.
39. Harrell FE Jr. Regression Modeling Strategies: With Applications to Linear Models, Logistic and Ordinal Regression, and Survival Analysis. Springer; 2015.
40. Steyerberg EW. Clinical Prediction Models: A Practical Approach to Development, Validation, and Updating. Springer; 2019.
41. Pepe MS. The Statistical Evaluation of Medical Tests for Classification and Prediction. Oxford University Press; 2003.
42. Baksh SA, Muhammad S, Parvez U, Shirazi B, Khan MA. Impact of the Laparoscopic Approach on Liver Function Tests: Comparison of Elective Biliary and Non-biliary Procedures. Cureus. 2025 Mar 31;17(3):e81500. doi: 10.7759/cureus.81500. PMID: 40166793; PMCID: PMC11956381.
43. Sarla GS, Sunkar SM. Effect of age of patient and duration of laparoscopic cholecystectomy on liver function tests. J Clin Med Res. 2024;6(2):277-87.
44. Feller D, Wingbermuhle R, Berg B, Vigdal ØN, Innocenti T, Grotle M, Ostelo R, Chiarotto A. Improvements are needed in the adherence to the TRIPOD statement for clinical prediction models for patients with spinal pain or osteoarthritis: a meta-research study. J Pain. 2024:104624.
45. Ghaferi AA, Schwartz TA, Pawlik TM. STROBE reporting guidelines for observational studies. JAMA Surg. 2021;156(6):577-8.
46. Boileau P, Qi NT, van der Laan MJ, Dudoit S, Leng N. A flexible approach for predictive biomarker discovery. Biostatistics. 2023;24(4):1085-1105.
47. Mi X, Zou B, Zou F, Hu J. Permutation-based identification of important biomarkers for complex diseases via machine learning models. Nat Commun. 2021;12(1):3008.
2. Strasberg SM. Clinical practice. Acute calculous cholecystitis. N Engl J Med. 2008;358(26):2804-11.
3. Sakorafas GH, Tsiotou AG, Farley DR, et al. Changes in liver function tests after laparoscopic cholecystectomy. Br J Surg. 1999;86(8):960-3.
4. Choudhury U, Dutta PS. Alterations in liver enzymes in the postoperative period following laparoscopic and open cholecystectomy. J Clin Diagn Res. 2023;17(6):PC14-PC17.
5. Hu B, Yang XR, Xu Y, et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20(23):6212-22.
6. Li MJ, Zhao TX, Wang J, et al. Role of systemic immune-inflammation index in predicting postoperative complications in colorectal cancer. World J Clin Cases. 2022;10(15):4810-18.
7. Collins GS, Reitsma JB, Altman DG, Moons KG. Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD): the TRIPOD statement. BMJ. 2015;350:g7594.
8. Jean-Antony S. Acute Cholecystitis: The Evaluation of Treatment Outcomes and Prognostic Factors. Master's thesis, Lithuanian University of Health Sciences (Lithuania); 2022.
9. Deleu S, Arnauts K, Machiels K, Huys G, Thevelein J, Raes J, Vermeire S. High acetate concentration reduces inflammation in organoid-derived epithelial monolayer from patients with ulcerative colitis (or UC patients). Acta Gastro-Enterologica Belgica. 2022;85(1):Fasc.
10. Ahmed M, Abdallah SA. Effect of different levels of intraperitoneal pneumoperitoneum on liver enzymes during laparoscopic cholecystectomy. Med J Cairo Univ. 2022;90(3):547-56.
11. Salati SA. Liver enzyme alterations after laparoscopic cholecystectomy (LC)–a study. J Health Sci Res. 2022;7(2):24-7.
12. He K, Si L, Pan X, Sun L, Wang Y, Lu J, Wang X. Preoperative systemic immune–inflammation index (SII) as a superior predictor of long-term survival outcome in patients with stage I–II gastric cancer after radical surgery. Front Oncol. 2022;12:829689.
13. Tudor MS, Gheorman V, Simeanu GM, Dobrinescu A, Pădureanu V, Dinescu VC, Forțofoiu MC. Evolutive models, algorithms and predictive parameters for the progression of hepatic steatosis. Metabolites. 2024;14(4):198.
14. Trebicka J, Hernaez R, Shawcross DL, Gerbes AL. Recent advances in the prevention and treatment of decompensated cirrhosis and acute-on-chronic liver failure (ACLF) and the role of biomarkers. Gut. 2024;73(6):1015-24.
15. Nair RT, Chan A, Morgan MA, Itani M, Ganeshan D, Arif-Tiwari H, El-Haddad E, Sabujan A, Dawkins AA. Biliary complications of surgical procedures: what the radiologist needs to know. Abdom Radiol. 2024:1-21.
16. Giakoustidis A, Papakonstantinou M, Gkoutzios C, Chatzikomnitsa P, Gkaitatzi AD, Myriskou A, Bangeas P, Loufopoulos PD, Papadopoulos VN, Giakoustidis D. Transient elevation of liver function tests and bilirubin levels after laparoscopic cholecystectomy. Medicina. 2024;60(11):1885.
17. Mannam R, Narayanan RS, Bansal A, Yanamaladoddi VR, Sarvepalli SS, Vemula SL, Aramadaka S. Laparoscopic cholecystectomy versus open cholecystectomy in acute cholecystitis: a literature review. Cureus. 2023;15(9).
18. Liu CQ, Yu ZB, Gan JX, Mei TM. Preoperative blood markers and intra-abdominal infection after colorectal cancer resection. World J Gastrointest Surg. 2024;16(2):451.
19. Shevchenko I, Grigorescu CC, Serban D, Cristea BM, Simion L, Gherghiceanu F, Costea AC, Dumitrescu D, Alius C, Tudor C, Onisai M. The value of systemic inflammatory indices for predicting early postoperative complications in colorectal cancer. Medicina. 2024;60(9):1481.
20. Jiao Y, Zhang X, Liu M, Sun YE, Ma Z, Gu X, Gu W, Zhu W. Systemic immune-inflammation index within the first postoperative hour as a predictor of severe postoperative complications in upper abdominal surgery: a retrospective single-center study. BMC Gastroenterol. 2022;22(1):403.
21. Gu P, Xu P, Chen Y, Li J, Sun H, Xu H, Lu Q. The predictive value of pan-immune inflammatory index for early recurrence of atrial fibrillation after cryoablation. BMC Cardiovasc Disord. 2024;24(1):669.
22. Tejeda-Herrera D, Caballero-Alvarado J, Zavaleta-Corvera C. The American College of Surgeons-National Surgical Quality Improvement Program calculator and surgical apgar as predictors of post-cholecystectomy complications. ABCD Arq Bras Cir Dig. 2024;37:e1862.
23. Spota A, Hassanpour A, Shlomovitz E, Gomez D, Al-Sukhni E. Acute cholecystitis management at a tertiary care center: are we following current guidelines? Langenbecks Arch Surg. 2024;409(1):323.
24. Rasslan R, Dos Santos JP, Menegozzo CA, Pezzano AV, Lunardeli HS, dos Santos Miranda J, Utiyama EM, Damous SH. Outcomes after emergency abdominal surgery in COVID-19 patients at a referral center in Brazil. Updates Surg. 2021;73(4):763-8.
25. Leiby J. Advancement and Application of Deep Learning Techniques for Biomedical Image Analysis: Diagnostics, Risk, and Biomarker Prediction. Doctoral dissertation, University of Pennsylvania; 2023.
26. Zhang X, Yue P, Zhang J, Yang M, Chen J, Zhang B, Luo W, Wang M, Da Z, Lin Y, Zhou W. A novel machine learning model and a public online prediction platform for prediction of post-ERCP-cholecystitis (PEC). EClinicalMedicine. 2022;48.
27. Wasilewski T, Kamysz W, Gębicki J. AI-assisted detection of biomarkers by sensors and biosensors for early diagnosis and monitoring. Biosensors. 2024;14(7):356.
28. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453-7.
29. Hong YM, Yoon KT, Cho M. Systemic immune-inflammation index predicts prognosis of sequential therapy with sorafenib and regorafenib in hepatocellular carcinoma. BMC Cancer. 2021;21:569. doi:10.1186/s12885-021-08124-9.
30. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205-13.
31. Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49(12):1373-9.
32. Jomrich G, Gruber ES, Winkler D, et al. Systemic immune-inflammation index (SII) predicts poor survival in pancreatic cancer patients undergoing resection. J Gastrointest Surg. 2020;24:610–618. doi:10.1007/s11605-019-04187-z.
33. Hasukic S, Kosuta D, Muminhodzic K. Comparison of postoperative hepatic function between laparoscopic and open cholecystectomy. Med Princ Pract. 2005;14(3):147-50.
34. Guven HE, Oral S. Liver enzyme alterations after laparoscopic cholecystectomy. J Gastrointestin Liver Dis. 2007;16(4):391-4.
35. Morino M, Giraudo G, Festa V. Alterations in hepatic function during laparoscopic surgery: an experimental clinical study. Surg Endosc. 1998;12(7):968-72.
36. Varma KR, Rabindranath RM, Bibekananda BD, Patra KK. Transient Alterations in Liver Enzymes Following Laparoscopic Cholecystectomy: Impact of Carbon Dioxide Pneumoperitoneum Duration in a Prospective Cohort. Journal of Contemporary Clinical Practice. 2025 Aug;11(8):266-272. .
37. Qi Q, Zhuang L, Shen Y, et al. A novel systemic immune-inflammation index predicts prognosis in patients after curative resection for gastric cancer. Clin Cancer Res. 2017;23(17):5504-12.
38. Jiang N, Deng JY, Liu Y. Systemic immune-inflammation index as a prognostic marker in colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis. 2021;36(5):1037-45.
39. Harrell FE Jr. Regression Modeling Strategies: With Applications to Linear Models, Logistic and Ordinal Regression, and Survival Analysis. Springer; 2015.
40. Steyerberg EW. Clinical Prediction Models: A Practical Approach to Development, Validation, and Updating. Springer; 2019.
41. Pepe MS. The Statistical Evaluation of Medical Tests for Classification and Prediction. Oxford University Press; 2003.
42. Baksh SA, Muhammad S, Parvez U, Shirazi B, Khan MA. Impact of the Laparoscopic Approach on Liver Function Tests: Comparison of Elective Biliary and Non-biliary Procedures. Cureus. 2025 Mar 31;17(3):e81500. doi: 10.7759/cureus.81500. PMID: 40166793; PMCID: PMC11956381.
43. Sarla GS, Sunkar SM. Effect of age of patient and duration of laparoscopic cholecystectomy on liver function tests. J Clin Med Res. 2024;6(2):277-87.
44. Feller D, Wingbermuhle R, Berg B, Vigdal ØN, Innocenti T, Grotle M, Ostelo R, Chiarotto A. Improvements are needed in the adherence to the TRIPOD statement for clinical prediction models for patients with spinal pain or osteoarthritis: a meta-research study. J Pain. 2024:104624.
45. Ghaferi AA, Schwartz TA, Pawlik TM. STROBE reporting guidelines for observational studies. JAMA Surg. 2021;156(6):577-8.
46. Boileau P, Qi NT, van der Laan MJ, Dudoit S, Leng N. A flexible approach for predictive biomarker discovery. Biostatistics. 2023;24(4):1085-1105.
47. Mi X, Zou B, Zou F, Hu J. Permutation-based identification of important biomarkers for complex diseases via machine learning models. Nat Commun. 2021;12(1):3008.
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| Acute calculous cholecystitis Perioperative liver function tests Postoperative complications Risk prediction model Systemic immune-inflammation index | ||
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How to Cite
1.
Zhang Y, Zhou Y, Hou L, Liu Y. Modeling Post-cholecystitis Complication Risk from Perioperative Liver Function and Immune-inflammation Indicators. Iran J Allergy Asthma Immunol. 2025;:1-14.
