Signa Vitae. 2025; 21(2): 60-69. doi: 10.22514/sv.2024.134
Original Research

Predictive value of inflammatory indices in acute cholecystitis: a retrospective study of gallstone detection and outcome assessment

Mehmet Göktuğ Efgan1,*,, Ejder Saylav Bora1, Semih Musa Coşkun1, Süleyman Kırık1, Ahmet Kayalı1

1Izmir Katip Çelebi University Department of Emergency Medicine, 35100 Izmir, Turkey

*Corresponding Author(s):mehmetgoktug.efgan@ikcu.edu.tr (Mehmet Göktuğ Efgan)

History Submitted: 11 July 2024 | Accepted: 14 August 2024 | Published: 08 February 2025
Copyright:  ©2025 The Author(s). Published by MRE Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Collapse table of contents

Abstract

Background: This retrospective observational study investigates the predictive value of inflammatory indices Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR) and Systemic Inflammatory Index (SII) for detecting gallstones and forecasting outcomes in patients with acute cholecystitis (AC). Methods: Conducted from 01 September 2022, to 01 September 2023, the research involved patients aged 18 and older diagnosed with AC in an emergency department, excluding those with overlapping pathologies or insufficient data. The study employed hemogram-based indices to explore their correlation with the presence of gallstones and the severity of AC, assessing outcomes such as hospitalization duration and the necessity for surgical intervention. Results: Findings demonstrated that high NLR and SII values significantly correlated with severe outcomes and increased hospitalization rates, while SII exhibited the highest accuracy in predicting mortality. Moreover, the study uniquely identified the Systemic Inflammatory Response Index (SIRI) as a significant marker for gallstone presence. Conclusions: Inflammatory indices like NLR, PLR and SII can be practical prognostic tools in managing AC, potentially guiding clinical decisions regarding immediate surgical needs and overall patient management. This suggests a broader application for these indices in emergency and surgical settings, improving diagnostic accuracy and treatment strategies.

Keywords:Acute cholecystitis;Gallstones;Systemic inflammatory index;Systemic inflammatory response index;Neutrophil-lymphocyte ratio;Platelet-lymphocyte ratio
PDF(4.86 MB)|EndNote (RIS)|BibTeX|RefMan|RefWorks

Cite this article

Mehmet Göktuğ Efgan, Ejder Saylav Bora, Semih Musa Coşkun, Süleyman Kırık, Ahmet Kayalı. Predictive value of inflammatory indices in acute cholecystitis: a retrospective study of gallstone detection and outcome assessment. Signa Vitae. 2025; 21(2): 60-69. doi: 10.22514/sv.2024.134

1. Introduction

Acute cholecystitis (AC) is the gradual inflammation of the gallbladder due to gallstones blocking the cystic duct. Symptoms range from congestion and swelling to bleeding and tissue death [1]. Failure to promptly address the issue can result in heightened morbidity, as it may progress to severe cholecystitis, characterized by gangrenous alteration, abscess development, and gallbladder perforation [2]. AC is more likely to occur in individuals who are over the age of 60, male, have cardiovascular disease, diabetes mellitus or a history of cerebrovascular injury [3].

AC is primarily caused by inflammation and typically follows a mild symptomatic course; it can also manifest with an additional severe symptomatic course, leading to increased mortality and morbidity, mainly when there are delays in diagnosis [4]. The diagnosis of AC can be promptly established through clinical and medical examinations, laboratory tests, and imaging procedures [5]. While imaging techniques for diagnosing the disease are advancing, there is still a need for additional diagnostic methods to accurately determine both the diagnosis and the extent of the disease [4, 5].

Although access to radiological methods like computed tomography (CT) and ultrasonography (USG) is more accessible today, many centers need to be aware of alternative imaging methods. Especially in primary healthcare institutions [6], it is challenging to diagnose abdominal pain differently.

In acute abdominal pain, biochemical values such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), amylase, and lipase may take time to increase [7]. In these cases, we do not have a supporting parameter other than examination for patients with right upper quadrant pain and Murphy (+) on examination. In the absence of a firm evidence-level diagnosis, the physician needs help with referral. Loss of time in this process may lead to undesirable situations, such as complications of the patient’s abdominal pain.

There is ongoing research on rapid and straightforward diagnostic markers, as the significance of early prediction of AC diagnosis is well recognized. To predict the prognosis of inflammatory conditions, several scores have been suggested, such as C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), monocyte lymphocyte ratio (MLR), systemic inflammatory index (SII) and systemic inflammatory response index (SIRI), are widely used in the diagnostic procedure [8, 9, 10]. The release of arachidonic acid metabolites and platelet-activating factors caused by inflammation leads to an increase in neutrophils. In contrast, the stress induced by cortisol leads to a decrease in lymphocytes. Therefore, the ratio of this parameter accurately reflects the underlying inflammatory process [11].

Cholesterol gallstones are linked to heightened inflammation and a thickened mucus layer in the gallbladder wall, indicating that inflammation is an initial occurrence in the development of gallstones [12]. The severity of oxidative stress in patients with choledocholithiasis is correlated with inflammation parameters and biochemical markers of cholestasis [13].

In this study, we aim to discover the best prognostic parameters between the inflammatory indexes for acute cholecystitis and to detect the predictive power of the presence of gallstones with inflammatory index ratios.

2. Materials and methods

2.1 Study design

This study was designed as a retrospective observational study. The study included patients admitted to the emergency department between 01 September 2022 and 01 September 2023.

2.2 Study population

Our study included patients aged 18 years and older who presented to the emergency department and were diagnosed with acute cholecystitis. Among these patients, we excluded patients with additional pathologies that may cause abdominal pain, additional infections, pregnant and/or lactating women, lack of data, history of any malignancy or hematologic disease, bone marrow pathology and history of anti-inflammatory and/or immunosuppressive drug use. Patients referred to an external center and for whom no outcome information was available were also excluded.

2.3 Outcomes

The primary outcome of this study is the predictability of the presence of stones in patients with acute cholecystitis using inflammatory indices. The secondary outcome is to investigate the usefulness of inflammatory indices as prognostic indicators in patients with acute cholecystitis and the most robust index in between.

2.4 Data collection

Patient records were accessed through the hospital information management system to determine which patients should be included in the study. In order to identify patients diagnosed with acute cholecystitis in the emergency department during the specified date range, a search was performed using acute cholecystitis diagnosis codes in the hospital information management system. A total of 288 patients were identified. Of these patients, 39 were excluded because of a history of malignancy, 21 because of missing data, seven because of a history of hematologic disease, two because of pregnancy and one because of receiving immunosuppressive therapy. The remaining 218 patients were included in the study. Age, gender, laboratory data, imaging data, length of hospitalization, mortality and comorbidities of all patients were recorded on the data recording form for statistical analysis.

2.5 Calculation of data

In the study, calculations were performed using the hemogram results obtained for each case. The marked parameters were peripheral platelet (P), neutrophil (N), lymphocyte (L) and monocyte (M) counts. The ratios calculated based on these values are NLR (N/L), PLR (P/L), MLR (M/L), SII ((P × N)/L), SIRI (N × M/L), Multi Inflammatory Index (MII-1) (NLR × CRP), MII-2 (PLR × CRP) and MII-3 (SII × CRP).

2.6 Statistical analysis

After the data collection process, the data will be digitized and statistically analyzed. IBM SPSS Statistics 28.0 (IBM Corporation, Armonk, NY, USA) will be used for all analyses. p values less than 0.05 were considered significant, and all statistics were performed at a 95% confidence interval. Descriptive statistics will be presented as frequency, percentage, mean, standard deviation, median, minimum and maximum values. The Shapiro-Wilk test will test normality assumptions, skewness, kurtosis values and Quantile-Quantile (Q-Q) plots. The participant’s data will be compared with the Independent Samples t Test to if they fit the normal distribution and with the Mann-Whitney U Test if they do not.

3. Results

A total of 218 patients were included in the study, and 94 (43.12%) were female. The mean age of the whole group was 59.49 ± 15.79 years. 183 (83.94%) patients had stones on USG. Hospitalization was given to 176 (80.73%) of the patients. 28 (12.84%) patients needed an urgent operation, and 4 (1.83%) patients ended up as exitus. All descriptive characteristics of the patients are presented in Table 1.

Table 1.Descriptive statistics of patients.
Statistics
Age59.49 ± 15.79
Gender
Male124 (56.88%)
Woman94 (43.12%)
Systolic BP137.09 ± 25.34
Diastolic BP73.58 ± 12.29
Pulse94.12 ± 55.63
Fire37.54 ± 4.66
WBC14.51 ± 5.68
NEU11.67 ± 5.54
LYM1.64 ± 1.38
MONO1.06 ± 0.65
PLT274.95 ± 90.94
HMG13.08 ± 1.95
BUN18.14 ± 11.64
CRE1.44 ± 3.97
NA136.10 ± 3.93
CRP104.49 ± 99.69
Stone on USG
Yes183 (83.94%)
None35 (16.06%)
Pericholecystic Fluid on USG
Yes90 (41.28%)
None128 (58.72%)
Hydropic sac on USG
Yes143 (65.60%)
None75 (34.40%)
Sac wall thickness increase on USG
Yes193 (88.53%)
None25 (11.47%)
Discharge/Admission
Discharge30 (13.76%)
Admission176 (80.73%)
Treatment Refusal12 (5.50%)
Service/ICU
Service166 (93.26%)
ICU12 (6.74%)
Operation
Performed28 (12.84%)
None190 (87.16%)
Time spent in the emergency room (h)6.39 ± 3.61
Time spent in the ward/ICU (d)7.45 ± 8.90
Outcome Discharge/Exitus
Discharge214 (98.17%)
Exit4 (1.83%)
BP: arterial blood pressure; WBC: White Blood Cell; NEU: Neutrophil; LYM: lymphocyte; MONO: Monocyte; PLT: platelet; HMG: hemoglobin; BUN: blood urea nitrogen; CRE: Creatinine; NA: sodium; CRP: C-reaktif protein; USG: ultrasonography; ICU: intensive care unit.

The results of the Receiver Operating Characteristic (ROC) curve analysis for the usefulness of all values in predicting outcomes are presented in Table 2 and Fig. 1. NLR, PLR, SII, MII-1, MII-2 and MII-3 are appropriate and statistically significant for this purpose. Table 2 presents the optimum cutoff values for predicting the endpoints of all variables and the sensitivities and specificities for these cutoff values.

Table 2.Cutoff scores, AUC value, sensitivity, selectivity and statistical significance of NLR, PLR, MLR, SII, SIRI, MII-1, MII-2 and MII-3 parameters by endpoint group.
Test Result VariablesCutoffAUCStd. ErrorpAsymptotic 95% Confidence IntervalSensitivitySpecificity
Lower BoundUpper Bound
NLR>12.3910.8350.0390.0220.7590.912100.074.3
PLR>266.6660.8560.0350.0150.7880.925100.078.0
MLR>0.6980.6520.0550.2980.5450.759100.050.5
SII>4631.2930.8910.0230.0070.8470.936100.086.0
SIRI>10.8730.7410.0480.0990.6460.835100.062.1
MII-1>1921.6420.8740.0420.0100.7910.957100.077.1
MII-2>39,629.7290.9040.0380.0060.8300.978100.079.4
MII-3>619,804.7070.9240.0300.0040.8650.984100.083.6
AUC: Area Under the Curve; Std.: standard; NLR: Neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; MLR: monocyte lymphocyte ratio; SII: Systemic Immune-Inflammation Index; SIRI: Systemic Inflammation Response Index; MII: Multi Inflammatory Index. Statistically significant ones are written in bold.
ROC curve analysis of NLR, PLR, MLR, SII, SIRI, MII-1, MII-2 and 
MII-3 parameters plotted according to outcome. ROC: Receiver Operating 
Characteristic; NLR: Neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; 
MLR: monocyte lymphocyte ratio; SII: Systemic Immune-Inflammation Index; SIRI: 
Systemic Inflammation Response Index; MII: Multi Inflammatory Index.

Fig. 1.ROC curve analysis of NLR, PLR, MLR, SII, SIRI, MII-1, MII-2 and MII-3 parameters plotted according to outcome. ROC: Receiver Operating Characteristic; NLR: Neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; MLR: monocyte lymphocyte ratio; SII: Systemic Immune-Inflammation Index; SIRI: Systemic Inflammation Response Index; MII: Multi Inflammatory Index.

Table 3 and Fig. 2 present an ROC curve analysis of all inflammatory parameters for predicting the presence or absence of stones on USG. Among all variables, SIRI was found to be the only statistically significant marker for predicting the presence of stones on USG. The optimum cutoff value for the SIRI variable in predicting the presence of stones on USG was >5.924, with a sensitivity of 61.75% and a specificity of 65.71%.

Table 3.Cutoff scores, AUC value, sensitivity, selectivity, and statistical significance of NLR, PLR, MLR, SII, SIRI, MII-1, MII-2 and MII-3 parameters by stone group on USG Tables should be placed in the main text near the first time they are cited.
Test Result VariablesCutoffAUCStd. ErrorpAsymptotic 95% Confidence IntervalSensitivitySpecificity
Lower BoundUpper Bound
NLR>4.6260.5400.0580.4510.4270.65375.4040.00
PLR≤155.8820.4080.0480.0850.3130.50338.3080.00
MLR>0.6980.5540.0560.3090.4450.66453.6062.90
SII>1615.1730.5480.0560.3670.4390.65760.7054.30
SIRI>5.9240.6170.0570.0290.5050.72861.7565.71
MII-1>83.8910.5800.0550.1320.4740.68779.8040.00
MII-2>4157.6080.5520.0530.3320.4470.65672.6842.86
MII-3>30,214.0350.5870.0530.1020.4830.69276.5045.71
AUC: Area Under the Curve; Std.: standard; NLR: Neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; MLR: monocyte lymphocyte ratio; SII: Systemic Immune-Inflammation Index; SIRI: Systemic Inflammation Response Index; MII: Multi Inflammatory Index. Statistically significant ones are written in bold.
ROC curve analysis of NLR, PLR, MLR, SII, SIRI, MII-1, MII-2 and 
MII-3 parameters according to the prediction of stone presence on USG. ROC: 
Receiver Operating Characteristic; NLR: Neutrophil lymphocyte ratio; PLR: 
platelet lymphocyte ratio; MLR: monocyte lymphocyte ratio; SII: Systemic 
Immune-Inflammation Index; SIRI: Systemic Inflammation Response Index; MII: Multi 
Inflammatory Index.

Fig. 2.ROC curve analysis of NLR, PLR, MLR, SII, SIRI, MII-1, MII-2 and MII-3 parameters according to the prediction of stone presence on USG. ROC: Receiver Operating Characteristic; NLR: Neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; MLR: monocyte lymphocyte ratio; SII: Systemic Immune-Inflammation Index; SIRI: Systemic Inflammation Response Index; MII: Multi Inflammatory Index.

Table 4 and Fig. 3 present the ROC curve analysis of inflammatory parameters in predicting hospitalization or discharge of acute cholecystitis patients from the emergency department. The use of all parameters for this purpose is appropriate and statistically significant. Table 4 presents the optimum cutoff values for predicting the endpoints of all variables and the sensitivities and specificities for these cutoff values.

Table 4.Cutoff scores, AUC value, sensitivity, selectivity, and statistical significance of NLR, PLR, MLR, SII, SIRI, MII-1, MII-2 and MII-3 parameters by discharge/hospitalization group.
Test Result VariablesCutoffAUCStd. ErrorpAsymptotic 95% Confidence IntervalSensitivitySpecificity
Lower BoundUpper Bound
NLR>3.7970.6720.0570.0030.5610.78386.9043.30
PLR>138.2810.6220.0560.0320.5130.73178.4050.00
MLR>0.4310.6450.0630.0110.5210.76880.1056.70
SII>1176.2500.6480.0560.0100.5380.75876.7053.30
SIRI>4.0590.6710.0570.0030.5600.78376.1063.30
MII-1>289.3710.6840.0560.0010.5740.79567.6073.30
MII-2>6082.4440.6800.0550.0020.5720.78772.7066.70
MII-3>79,350.7170.6870.0550.0010.5800.79465.3076.70
AUC: Area Under the Curve; Std.: standard; NLR: Neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; MLR: monocyte lymphocyte ratio; SII: Systemic Immune-Inflammation; SIRI: Systemic Inflammation Response Index; MII: Multi Inflammatory Index. Statistically significant ones are written in bold.
ROC curve analysis plotted according to NLR, PLR, MLR, SII, 
SIRI, MII-1, MII-2 and MII-3 parameters and discharge/admission group. ROC: 
Receiver Operating Characteristic; NLR: Neutrophil lymphocyte ratio; PLR: 
platelet lymphocyte ratio; MLR: monocyte lymphocyte ratio; SII: Systemic 
Immune-Inflammation; SIRI: Systemic Inflammation Response Index; MII: Multi 
Inflammatory Index.

Fig. 3.ROC curve analysis plotted according to NLR, PLR, MLR, SII, SIRI, MII-1, MII-2 and MII-3 parameters and discharge/admission group. ROC: Receiver Operating Characteristic; NLR: Neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; MLR: monocyte lymphocyte ratio; SII: Systemic Immune-Inflammation; SIRI: Systemic Inflammation Response Index; MII: Multi Inflammatory Index.

ROC curve analysis of inflammatory parameters in predicting hospitalization of acute cholecystitis patients to the ward or intensive care unit is presented in Table 5 and Fig. 4. The use of NLR, PLR, SII, MII-1, MII-2 and MII-3 for this purpose is appropriate and statistically significant. The optimum cutoff values for predicting the endpoints of all variables and the sensitivities and specificities for these cutoff values are presented in Table 5.

Table 5.Cutoff scores, AUC value, sensitivity, selectivity and statistical significance of NLR, PLR, MLR, SII, SIRI, MII-1, MII-2 and MII-3 parameters by hospitalization to service /ICU Group.
Test Result VariablesCutoffAUCStd. ErrorpAsymptotic 95% Confidence IntervalSensitivitySpecificity
Lower BoundUpper Bound
NLR>13.6700.7890.0660.0010.6600.91775.080.1
PLR>266.6660.8340.0400.0010.7560.91283.378.9
MLR>0.8330.6290.0880.1380.4560.80166.764.5
SII>3413.7030.8010.0530.0010.6970.90583.377.7
SIRI>15.6200.6350.0930.1190.4530.81758.377.1
MII-1>1389.6600.7930.0690.0010.6580.92883.369.3
MII-2>31,538.2130.8090.0650.0010.6810.93783.370.5
MII-3>619,804.7070.8060.0690.0010.6710.94175.084.3
AUC: Area Under the Curve; Std.: standard; NLR: Neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; MLR: monocyte lymphocyte ratio; SII: Systemic Immune-Inflammation; SIRI: Systemic Inflammation Response Index; MII: Multi Inflammatory Index. Statistically significant ones are written in bold.
ROC curve analysis plotted according to NLR, PLR, SII, MII-1, 
MII-2 and MII-3 parameters and discharge/admission group. ROC: Receiver Operating 
Characteristic; NLR: Neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; 
MLR: monocyte lymphocyte ratio; SII: Systemic Immune-Inflammation; SIRI: Systemic 
Inflammation Response Index; MII: Multi Inflammatory Index.

Fig. 4.ROC curve analysis plotted according to NLR, PLR, SII, MII-1, MII-2 and MII-3 parameters and discharge/admission group. ROC: Receiver Operating Characteristic; NLR: Neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; MLR: monocyte lymphocyte ratio; SII: Systemic Immune-Inflammation; SIRI: Systemic Inflammation Response Index; MII: Multi Inflammatory Index.

4. Discussion

Accurately evaluating the seriousness of acute cholecystitis is crucial for optimizing treatment results and minimizing adverse postoperative incidents [14, 15, 16]. Localized inflammation and surgical trauma trigger metabolic and systemic inflammatory reactions, potentially resulting in systemic complications [9]. Gaining comprehension of inflammation and addressing the potential systemic imbalances it can induce is crucial for averting unfavorable consequences and avoiding unnecessarily extended hospital stays in cases involving AC.

The current study involved a comparative analysis of NLR, PLR, MLR, SII, SIRI, MII-1, MII-2 and MII-3 in determining their effectiveness in predicting severe inflammation in acute cholecystitis, the risk of complication, and choledocholithiasis outcomes. Although computed tomography (CT) and ultrasonography (USG) techniques are available, supplementary diagnostic methods are still required to improve diagnostic precision, particularly in primary healthcare facilities with limited resources. Discovering alternative markers, such as indicators of inflammation, shows potential in this context. Although the algorithms of diagnostic and therapeutic methods for the diagnosis and etiology of AC are known [17], there is no simple, inexpensive, and non-invasive method for early diagnosis and treatment, especially in centers where conventional methods are unavailable. In a study by Gojayev et al. [18], more than a thousand patients were evaluated for founding an early signal method for AC, and they describe that if the neutrophil-to-lymphocyte ratio (NLR) is higher than 5.65 and the total leukocyte count exceeds 8100/mm3, complications are 92% likely. The results of a systematic review and meta-analysis demonstrate that the Neutrophil-to-Lymphocyte Ratio (NLR) is notably elevated in patients with AC compared to those without, and it can serve as a reliable indicator for the presence of AC. Nevertheless, NLR may not accurately forecast the seriousness of AC due to constraints in the study’s statistical power [19]. On the other hand, in a study by Patel et al. [20], they describe a higher NLR as positively associated with an increased length of stay (LOS) in patients admitted with acute cholecystitis (AC), indicating that it can serve as a valuable indicator of the severity of the disease. In this study, we found that NLR greater than 3.797 were hospitalized to the service, >12.391 has a relation with mortality outcome and >13.67 has a relation with ICU hospitalization. This study’s results align with other results and confirm other studies.

The NLR, the ratio of platelets to lymphocytes (PLR), and the systemic inflammatory index (SII) are valuable indicators for determining the severity of AC. Among these, the NLR is the most effective in predicting advanced inflammation and the likelihood of progressing to more severe forms of the condition, surpassing the predictive capabilities of both the PLR and SII. There is a strong correlation between high NLR values and the occurrence of postoperative complications and sepsis [9].

Our analysis revealed that the SII demonstrated the highest performance in predicting mortality in AC, achieving an AUC of 0.891 when using a cutoff value greater than 4631.293. It demonstrates a high sensitivity of 100% but a high specificity of 86%. The SII also exhibits a strong predictive capacity for hospitalization, as indicated by an area under the curve (AUC) value of 0.801 and a cutoff value of 3413.703. It demonstrates a high sensitivity of 83.3% but a high specificity of 77.7%. Beliaev et al. [21] claim that patients with AC exhibit elevated levels of systemic inflammation response index (SIRI) and SII compared to controls. This indicates that SIRI and SII can be helpful to diagnostic markers in addition to CRP [21]. Moreover, Cakcak et al. [22] found that inflammatory markers such as SIRI and SII can forecast the seriousness of AC and assist in determining whether cholecystostomy, a less invasive alternative to cholecystectomy, is a suitable course of action.

Cholesterol concentrated in the gallbladder can precipitate and form gallstones in some abnormal conditions. Excessive absorption of water from bile, excessive absorption of bile salts and lecithin from bile, excessive secretion of cholesterol into bile, inflammation of the gallbladder epithelium, factors that promote and inhibit crystallization in gallbladder bile, mucin, prostaglandins, calcium and lack of motility play a role in the development of cholesterol stones [23, 24]. Cholecystokinin receptor defects in the gallbladder smooth muscle membrane, oxidative stress and inflammatory mediators lead to smooth muscle dysfunction and decreased motility [25, 26]. As inflammation increases, especially fluid and bile salt, absorption in the bile wall increases, and cholesterol begins to precipitate. Accordingly, stone formation increases and increases, inflammation increases, and these events enter a vicious cycle. The SIRI and its related indices, such as SII, are useful prognostic tools for various diseases, including cardiovascular events [27], cancer [28] and conditions characterized by acute inflammation [29, 30], such as acute cholecystitis, as in this study.

Depending on our study, the SIRI is the single inflammatory parameter that indicates gallstones. SIRI probably shows the chronic inflammation process and results. In addition to predicting the likelihood of gallstones, SIRI was also found to be insignificant for mortality and significant forward admission and intensive care unit stay. In SII, it was found to be significant for all. The only difference in the SII and SIRI formulations is the platelet and lymphocyte multiplier in the ratio’s denominator. This suggests that SIRI may be significant in chronic inflammatory processes leading to stone formation rather than acute inflammatory processes. As far as we know, this is the first time in the literature that a simple computable parameter such as SIRI has been used to assume the presence of gallstone.

This study shows that SIRI will be supportive in the absence of CT and USG, which are the gold standard for the diagnosis [31], by looking at the hemogram, which is a simple and inexpensive test to give a clue about the presence of bile stones. In addition, high SII will give an idea about the severity and outcome of AC and will strengthen our hand in hospitalization and discharge.

This article has some limitations. First, it has a single-center and retrospective design, which constitutes the most important limitation. Second, the study’s aim is to use inflammatory markers in primary health care centers, but it was conducted in a large research hospital. Studies that will include smaller centers are needed. In addition, the study was conducted on patients with a definitive diagnosis. Studies conducted with a control group may report more definitive results.

5. Conclusions

The results indicate that specific inflammatory markers, such as Neutrophil Lymphocyte Ratio, Platelet Lymphocyte Ratio and Systemic Inflammatory Index, show potential as prognostic indicators for acute cholecystitis. These markers can assist clinicians in making prompt decisions about patient management, such as assessing the necessity for immediate surgery or predicting the need for hospitalization. Moreover, this is the first study in which an inflammatory index was used to predict the existence of a foreign body like a gallstone. Further investigation may prioritize prospective studies with more extensive sample sizes to authenticate the results and investigate supplementary inflammatory markers.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Author contributions

MGE, ESB, SMC, SK, AK—conceptualization. MGE, ESB—methodology, data curation. SMC, SK, AK—software. MGE, ESB, SMC—validation. MGE, SK—formal analysis. MGE, SMC, AK—investigation. ESB, SMC, SK—resources; visualization. MGE, ESB, AK—writing–original draft preparation, project administration. ESB, SK—writing–review and editing; supervision. All authors have read and agreed to the published version of the manuscript.

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and approved by the Izmir Katip Celebi University Non-Interventional Research Ethics Committee (protocol code 0406 and date of approval: 21 September 2023). Consent for participation was obtained from all subjects.

Acknowledgment

Not applicable.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflicts of interest.

References

Adachi T, Eguchi S, Muto Y. Pathophysiology and pathology of acute cholecystitis: a secondary publication of the Japanese version from 1992. Journal of Hepato-Biliary-Pancreatic Sciences. 2022; 29: 212–216.

[Google Scholar]

Cho JY, Han HS, Yoon YS, Ahn KS. Risk factors for acute cholecystitis and a complicated clinical course in patients with symptomatic cholelithiasis. Archives of Surgery. 2010; 145: 329–333; discussion 333.

[Google Scholar]

Gallaher JR, Charles A. Acute cholecystitis: a review JAMA. JAMA. 2022; 327: 965–975.

[Google Scholar]

Cripps MW, Weber NT. Classification schemes for acute cholecystitis. Panamerican Journal of Trauma, Critical Care & Emergency Surgery. 2022; 11: 139–144.

[Google Scholar]

Delgado Nicolás MA, Peces Morate FJ. Analysis of the use of radiology in primary health care. Aten Primaria. 1996; 17: 52–56.

[Google Scholar]

Chisholm PR, Patel AH, Law RJ, Schulman AR, Bedi AO, Kwon RS, et al. Preoperative predictors of choledocholithiasis in patients presenting with acute calculous cholecystitis. Gastrointestinal Endoscopy. 2019; 89: 977–983.e2.

[Google Scholar]

Yildiz G, Selvi F, Bedel C, Zortuk Ö, Korkut M, Mutlucan UO. Systemic inflammation response index and systemic immune inflammation index for predicting acute cholecystitis. Indian Journal of Medical Specialities. 2023; 14: 88–92.

[Google Scholar]

Mok KW, Reddy R, Wood F, Turner P, Ward JB, Pursnani KG, et al. Is C-reactive protein a helpful adjunct in selecting patients for emergency cholecystectomy by predicting severe/gangrenous cholecystitis? International Journal of Surgery. 2014; 12: 649–653

[Google Scholar]

Serban D, Stoica PL, Dascalu AM, Bratu DG, Cristea BM, Alius C, et al. The significance of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammatory index (SII) in predicting severity and adverse outcomes in acute calculous cholecystitis. Journal of Clinical Medicine. 2023; 12: 6946.

[Google Scholar]

Uludağ SS, Akıncı O, Güreş N, Tosun Y, Şanlı AN, Zengin AK, et al. An investigation into the predictive role of serum inflammatory parameters in the diagnosis of complicated acute cholecystitis. Turkish Journal of Trauma and Emergency Surgery. 2022; 28: 818–823.

[Google Scholar]

Hareen TVK, Bhaskaran A, Jaswanthi AR. Neutrophil to lymphocyte ratio in diagnosing acute cholecystitis: a retrospective cohort study in a tertiary rural hospital. International Surgery Journal. 2017; 4: 372–376.

[Google Scholar]

Rege RV, Prystowsky JB. Inflammation and a thickened mucus layer in mice with cholesterol gallstones. Journal of Surgical Research. 1998; 74: 81–85.

[Google Scholar]

Damnjanović Z, Jovanović M, Nagorni A, Radojković M, Sokolović D 2nd, Damnjanović G, et al. Correlation of inflammation parameters and biochemical markers of cholestasis with the intensity of lipid peroxidation in patients with choledocholithiasis. Vojnosanit Pregl. 2013; 70: 170–176.

[Google Scholar]

Gomes CA, Junior CS, Di Saverio S, Sartelli M, Kelly MD, Gomes CC, et al. Acute calculous cholecystitis: review of current best practices. World Journal of Gastrointestinal Surgery. 2017; 9: 118–126. Erratum. World Journal of Gastrointestinal Surgery. 2017; 9: 214.

[Google Scholar]

Yilmaz S, Aykota MR, Ozgen U, Birsen O, Simsek S, Kabay B. Might simple peripheral blood parameters be an early indicator in the prediction of severity and morbidity of cholecystitis? Annals of Surgical Treatment and Research. 2023; 104: 332–338.

[Google Scholar]

Paul S, Khataniar H, Ck A, Rao HK. Preoperative scoring system validation and analysis of associated risk factors in predicting difficult laparoscopic cholecystectomy in patients with acute calculous cholecystitis: a prospective observational study. Turkish Journal of Surgery. 2022; 38: 375–381.

[Google Scholar]

Okamoto K, Suzuki K, Takada T, Strasberg SM, Asbun HJ, Endo I, et al. Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis. Journal of Hepato-Biliary-Pancreatic Sciences. 2018; 25: 55–72.

[Google Scholar]

Gojayev A, Karakaya E, Erkent M, Yücebaş SC, Aydin HO, Kavasoğlu L, et al. A novel approach to distinguish complicated and non-complicated acute cholecystitis: decision tree method. Medicine. 2023; 102: e33749.

[Google Scholar]

Kler A, Taib A, Hajibandeh S, Hajibandeh S, Asaad P. The predictive significance of neutro-phil-to-lymphocyte ratio in cholecystitis: a systematic review and meta-analysis. British Journal of Surgery. 2022; 407: 927–935.

[Google Scholar]

Patel K, Wagstaff A, Mirza S. PWE-076 Ratio of neutrophil to lymphocyte count as a predictor of length of stay in acute cholecystitis. Gut. 2015; 64: A245–A246.

[Google Scholar]

Beliaev AM, Angelo N, Booth M, Bergin C. Evaluation of neutrophil-to-lymphocyte ratio as a potential biomarker for acute cholecystitis. Journal of Surgical Research. 2017; 209: 93–101.

[Google Scholar]

Cakcak İE, Kula O. Predictive evaluation of SIRI, SII, PNI, and GPS in cholecystostomy application in patients with acute cholecystitis. Turkish Journal of Trauma and Emergency Surgery. 2022; 28: 940–946.

[Google Scholar]

Dowling RH. Review: pathogenesis of gallstones. Alimentary Pharmacology & Therapeutics. 2000; 14: 39–47.

[Google Scholar]

Portincasa P, Di Ciaula A, vanBerge-Henegouwen GP. Smooth muscle function and dysfunction in gallbladder disease. Current Gastroenterology Reports. 2004; 6: 151–162.

[Google Scholar]

Sipos P, Gamal EM, Blázovics A, Metzger P, Mikó I, Furka I. Free radical reactions in the gallbladder. Acta Chir Hung. 1997; 36: 329–330.

[Google Scholar]

Dengler DG, Sun Q, Harikumar KG, Miller LJ, Sergienko EA. Screening for positive allosteric modulators of cholecys-tokinin type 1 receptor potentially useful for management of obesity. SLAS Discovery. 2022; 27: 384–394.

[Google Scholar]

Han K, Shi D, Yang L, Wang Z, Li Y, Gao F, et al. Prognostic value of systemic inflammatory response index in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Annals of Medicine. 2022; 54: 1667–1677.

[Google Scholar]

Ye K, Xiao M, Li Z, He K, Wang J, Zhu L, et al. Preoperative systemic inflammation response index is an independent prognostic marker for BCG immunotherapy in patients with non-muscle-invasive bladder cancer. Cancer Medicine. 2023; 12: 4206–4217.

[Google Scholar]

Yun S, Yi HJ, Lee DH, Sung JH. Systemic inflammation response index and systemic immune-inflammation index for predicting the prognosis of patients with aneurysmal subarachnoid hemorrhage. Journal of Stroke and Cerebrovascular Diseases. 2021; 30: 105861.

[Google Scholar]

Matolo NM, LaMorte WW, Wolfe BM. Acute and chronic cholecystitis. Surgical clinics of North America. 1981; 61: 875–883.

[Google Scholar]

Cremer A, Arvanitakis M. Diagnosis and management of bile stone disease and its complications. Minerva Gastroenterol Dietol. 2016; 62: 103–129.

[Google Scholar]