European Journal of Cardiovascular Medicine

Acute pancreatitis is an inflammatory condition of the pancreas causing damage to the pancreatic tissue by causing early activation of digestive enzymes. It can lead to mild disease in most cases like oedematous pancreatitis to severe disease like acute severe necrotising pancreatitis requiring ICU(Intensive care unit) admission and causing death. Most common cause is gall stones followed by alcohol use. Gall stone pancreatitis is common in females whereas alcoholic pancreatitis is common in males. Smoking also plays an important role in pathogenesis of acute pancreatitis, it is considered as an independent risk factor in the causation of the disease [1]. There is an increased incidence of acute pancreatitis in the world due to lifestyle changes [2].

The process of acute pancreatitis starts in the acinar cells where trypsinogen is activated to trypsin before releasing into the duodenum. This causes subsequent activation of digestive enzymes in the pancreas leading to self-digestion. Trypsin also activates alternate pathways such as complement pathway, fibrinolysis extending the process outside the gland. There is also release of free radicals and proinflammatory cytokines like interleukin -6(IL 6),interleukin 4(IL 4), interleukin 8(IL 8), Platelet activating factor(PAF), tumor necrosis factor alpha(TNF alpha), leading to damage of the microcirculatory system, blood vessels and local tissue causing necrosis.[3] If the damage to the pancreas is extensive, there is release of these cytokines into the blood stream causing systemic complications like renal failure, lung injury, septic encephalopathy leading to ICU admission and increased mortality.

In mild diseases patient recovers without much complications, but in case of severe pancreatitis there are two stages where initially SIRS (Systemic inflammatory response syndrome) develops in first 2 weeks leading to release of cytokines. If the SIRS becomes severe in oncoming weeks, it causes release of cytokines into the blood stream and damages the endothelial barrier of the organs such as lungs leading to ARDS (Acute respiratory distress syndrome), kidney causing acute kidney injury, intestines causing bacterial translocation risking pancreatic infection and necrosis. This multiorgan damage caused by cytokine release is known as MODS (Multiorgan dysfunction syndrome)[4] leading to ICU admission and increased mortality in patients with acute pancreatitis.

Several markers are present which is used to assess the severity of acute pancreatitis. Most common are amylase, total leukocyte counts (TLC), lipase, c reactive protein, erythrocyte sediment rate (ESR), procalcitonin, IL 6, polymorphonuclear elastase (PMN) and many others. Among them CRP is considered as gold standard and is used in many hospitals worldwide [5]. Some of the biomarkers mentioned above are not used due to low accuracy, need for sophisticated equipments and higher costs.

Neutrophil lymphocyte ratio (NLR) is one of the new biomarkers that is emerging and is now used in various inflammatory diseases. It is easily accessible in a simple complete blood count (CBC) test that is available in various hospitals ranging from small remote clinics to big tertiary care centre. The early increase (<6 h) in NLR following acute physiological stress could confer on NLR the role of marker of acute stress earlier than other laboratory parameters (e.g., white blood cell count, bacteremia, C-reactive protein, CRP).[6]

NLR is a ratio between two absolute cell counts, any physiological state that differentially alters either neutrophils or lymphocytes will systematically alter the NLR. Such states include acute inflammation, hematological malignancies, immune deficiencies and immunomodulatory medication use.[7]

The normal range of NLR is not well defined in large population, but according to a study done by Patrice et al the normal NLR values in normal adults, non geriartric population , healthy adults ranges from 0.78 and 3.53[8].Here in this study the sample size was 413 healthy persons ranging from 21 years to 66 years. According to a study done by Baseem et al the average value of NLR was 2.15 which was similar to the study mentioned previously. In this study healthy participants 9247 participants were included in this study[9].

This is a prospective study done from January 2025 to April 2025 in tertiary care centre including 92 patients in this study. In this study we have included patients who present to the emergency with clinical findings of acute pancreatitis with raised levels of serum amylase and lipase raised three times of normal. Exclusion criteria included patients of chronic pancreatitis, acute on chronic pancreatitis and pancreatic carcinoma. The patient is examined and resuscitated in the emergency, admitted and the blood sample is drawn and sent for CBC and CRP on the day of admission .The patient is observed in the ward for any complications and on day 2 or 48hrs from time of admission the second sample of CBC and CRP is sent. CECT (Contrast enhanced computerised tomography) abdomen and pelvis is done 72 hrs from the time of admission or from the onset of symptoms. Modified CTSI (Computerised tomography severity scoring) is calculated from the cect scan and the CRP and NLR values is correlated. Prognosis of the patient is assessed, the procedures done, and complications developed during the hospital stay is documented. The presentation, comorbidities (diabetes, hypertension, hyperlipidaemia), habits are documented. Out of 103 patients 92 patients fit into the criteria and are included in this study. The primary objective was to correlate the NLR values and the severity of the pancreatitis at time of admission and after 48 hrs of admission. The study was approved by the institutional ethical committee.

Statistical Analysis

The collected data were entered  in the Microsoft Excel 2016  and  analysed with IBM SPSS Statistics for Windows, Version 29.0.(Armonk, NY: IBM Corp).To describe about the data descriptive statistics frequency analysis, percentage analysis were used for categorical variables and the mean & S.D were used for continuous variables. To find the significant difference between the bivariate samples in Paired groups the Paired sample t-test was used & for Independent groups the Independent sample t-test was used. For the multivariate analysis the one way ANOVA with Tukey's Post-Hoc test was used..To assess the relationship between the variables Pearson's Correlation was used.The Binary Logistics regression analysis was used to predict the influencing factors for the cause of Severeity. To find the significance in categorical data Chi-Square test was used similarly if the expected cell frequency is less than  5 in 2×2 tables then the Fisher's Exact was usedTo find the efficacy of the CT severity score with CRP & NLR to predict the Severe Acute Pancreatitis the Receiver Operating Characteristics curve(ROC) was used with Sensitivity,Specificity and cut-off. In all the above statistical tools the probability value .05 is considered as significant level.

                                            Diagnosis based on CECT scan

        CECT (contrast enhanced computerised tomography)

General Details:

Most of the patient enrolled into the study are males (85 out of 92) than females (7 out of 92). Most of the patients were admitted in emergency setting(75 out of 92 patients). The minimum age was 21 and maximum age was 80 years with mean age of 37 years which tells most of the patients were of younger age. Most common cause was found to be associated with consumption of alcohol, but involvement of gall stone as cause could not be ruled out. Biliary pancreatitis was of lesser prevalence (4 out of 92). Most of these patients recovered without any complications, 3 patients died whereas 32 patients had different complications. Hospital stay was longer for patients in severe category as compared to non-severe category out of which 13 patients had history of multiple admissions for acute pancreatitis with mean value of 2 admissions.

Comparison of CRP and NLR in severe and non-severe cases:

Paired t test is used to compare CRP and NLR at 0hrs and at 48hrs. Here CTSI is divided into severe and non-severe group (mild and moderate) for statistical purpose. The change in CRP in non-severe cases (135.3 ± 72.5 and 138.7 ± 73.2, respectively; p = 0.0005)and in severe cases(266.8 ± 110.3 and 264.7 ± 100.2;p=0.0005) at 0hrs and 48hrs. The change in NLR in non-severe cases(6.4 ± 2.3 and 6.8 ± 2.8; p = 0.0005) and in severe cases(10.3 ± 2.7 and 12.2 ± 2.8;p=0.0005) at 0hrs and 48hrs.Independent t test showed significant differences in CRP at 0 hrs(266.8 vs 135.3 mg/L, p = 0.0005) and 48hrs(264.7 vs 138.7 mg/L, p = 0.0005) and NLR AT 0hrs(10.3 vs 6.4, p = 0.0005) and at 48hrs(12.2 vs 6.8, p = 0.0005) between severe and non-severe cases. Both CRP and NLR showed significant increase in values in severe cases as compared to non-severe cases.

              Logistic Regression Analysis

              CRP: c reactive protein, NLR: neutrophil lymphocyte ratio

Comparision and correlation of CRP and NLR

For ANOVA analysis, patients was categorised into three categories based on CTSI (mild, moderate and severe). ANOVA results showed significant variation in CRP levels (0 hrs: F = 25.689, p = 0.0005; 48 hrs: F = 29.574, p = 0.0005) and in NLR values (0 hrs: F = 34.830, p = 0.0005; 48 hrs: F = 54.330, p = 0.0005). Tukey HSD post hoc analysis further confirmed these findings, with significant differences between Severe and Mild groups for both CRP (48 hrs: Mean Difference = 154.91, p = 0.0005) and NLR (48 hrs: Mean Difference = 6.72, p = 0.0005 These results highlight a progressive increase in inflammatory response markers correlating with  severity of the disease. CRP and NLR proved statistically significant in determining the severity of the disease particularly at 48hrs. Logistic regression showed NLR at 48hrs as a powerful independent predictor of severity withp = 0.001 and Exp(B) = 2.212(95% CI: 1.375–3.558) and CRP at 0hrs as early predictor of severity of the disease with p = 0.043 and Exp(B) = 1.021. This implies CRP is better at 0hrs and NLR is better at 48hrs predicting severity and prognosis of the disease.

Roc Curve Analysis

According to the ROC curve, NLR at 48hrs exhibited higher accuracy among all 4 parameters with AUC of 0.903 (95% CI: 0.841–0.965, p = 0.0005). At the early stage of disease CRP has high accuracy with AUC of 0.874 (95% CI: 0.803–0.945, p = 0.0005).CRP at 0hrs has high YoudenIndexwith 80% sensitivity and 78.9% specificity which can act as a useful clinical marker. At a 9.10 cut-off, NLR (48hrs) shows 80.0% sensitivity, 80.7% specificity, and AUC of 0.903 (95% CI: 0.841–0.965), indicating excellent diagnostic accuracy. This indicates that CRP can be used at 0hrs to establish the severity of the disease whereas NLR can be used as a prognostic marker at 48hrs to guide the treatment of the patient.

The incidence of acute pancreatitis is increasing overtime from past 56 years at rate of 3.07% per year causing burden to health care system all around the world [10]. Most of the diagnosed cases are mild with less to one complications and less hospital stay. Some cases progress to severe pancreatitis causing increased morbidity and mortality. Such cases are to be identified sooner and early treatment should be started to reduce morbidity. Hence early prediction of progression to severe pancreatitis is important. Many scoring systems and biochemical markers are present to predict the severity and prognosis of acute pancreatitis, but they also have their own drawbacks. RANSONS, APACHE II are efficient, but the complexity and their time of completion makes it tedious task to finish the scoring system. Biochemical markers like CRP, IL 6, procalcitonin, TNF are used, but are non specific and are usually not available in all centres, and also is costly for small setups. NLR is a recent marker that can be easily calculated by complete blood count and is shown to be useful in predicting the severity of inflammation in many conditions. NLR has been known to predict prognosis in cardiovascular diseases[11], colorectal cancers[12], gynaecological cancer[13], stroke[14]and many other conditions. Since severe pancreatitis is associated with sepsis NLR can be used in predicting the prognosis[15]. Here in this study out of 92 patients only 4 patients are diagnosed with gall stone pancreatitis. This is contradictory to the common cause of pancreatitis as gall stone pancreatitis. This may be due referral of severe cases from primary and secondary health care centres or due to passage of gall stone. Many of these patients came to the hospital as a referral cases after primary treatment from a smaller setup. Most of the mild to moderate cases get treated at primary setups. Alcoholic pancreatits tend to be more severe than gall stone pancreatitis due to its severe complications like pseudocyst, necrosis, venous thrombosis[16] . Hence most of alcoholic pancreatitis are referred to tertiary care centre due to its severity and poor prognosis. Among the complications in this study venous thrombosis, diabetes mellitus and decompensated liver disease was more common. Some of these patients also had history of multiple admissions for the same cause revealing multiple attacks of acute pancreatitis. According to the scatter plot shown above CRP plots, CRP at 48hours (R² = 0.429) showed a slightly stronger correlation with CT severity than CRP at 0 hours (R² = 0.407). NLR at 48 hrs shows stronger correlation at both 0hrs (R² = 0.446) and 48 hrs with 48 hrs (R² = 0.528) being most significant indicating NLR at 48hrs is significant in predicting the prognosis and severity of acute pancreatitis.

According to a study done by Hyun Sok Park et al, NLR showed similar sensitivity (82%) and specificity (70%) indicating it is a reliable and independent marker in predicting the severity of acute pancreatitis.

Drawback of this study is mainly of the small sample size. With the sample size of 92 patients the statistical accuracy could not be achieved. Due to small sample size and referral to tertiary care centre, most of the gall stone pancreatitis have not been reported. This study was done in a single centre only, study in multiple centre with more sample size may yield more accurate results.

NLR and CRP are bot valuable in assessing the severity of pancreatitis. In this study CRP was to be significant in predicting severity in early stages of the disease and NLR is better in determining the prognosis of acute pancreatitis. NLR as a biomarker is proven to be significant in predicting the systemic inflammatory syndrome in many diseases. Studied with high sample size size and multicentric trials should be conducted to prove its significance.

1.       Majumder, Shounak MD*; Gierisch, Jennifer M. PhD, MPH†‡; Bastian, Lori A. MD, MPH*§. The Association of Smoking and Acute Pancreatitis: A Systematic Review and Meta-analysis. Pancreas 44(4):p 540-546, May 2015. | DOI: 10.1097/MPA.0000000000000301

2.       Yadav, D., Vege, S.S. and Chari, S.T. (2014). Epidemiology of Pancreatitis. In GI Epidemiology (eds N.J. Talley, G.R. Locke, P. Moayyedi, J. West, A.C. Ford and Y.A. Saito). https://doi.org/10.1002/9781118727072.ch27

3.       Cruz-Santamaría DM, Taxonera C, Giner M. Update on pathogenesis and clinical management of acute pancreatitis. World J GastrointestPathophysiol. 2012 Jun 15; 3(3):60-70. doi: 10.4291/wjgp.v3.i3.60. PMID: 22737590; PMCID: PMC3382704.

4.       Al Mofleh IA. Severe acute pancreatitis: pathogenetic aspects and prognostic factors. World J Gastroenterol. 2008 Feb 7; 14(5):675-84. doi: 10.3748/wjg.14.675. PMID: 18205255; PMCID: PMC2683992.

5.       Staubli, S. M., Oertli, D., &Nebiker, C. A. (2015). Laboratory markers predicting severity of acute pancreatitis. Critical Reviews in Clinical Laboratory Sciences, 52(6), 273–283. https://doi.org/10.3109/10408363.2015.1051659

6.       Buonacera A, Stancanelli B, Colaci M, Malatino L. Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases. Int J Mol Sci. 2022 Mar 26; 23(7):3636. doi: 10.3390/ijms23073636. PMID: 35408994; PMCID: PMC8998851.

7.       Nicholas H Adamstein, Paul M Ridker, The neutrophil–lymphocyte ratio: considerations for clinical application, European Heart Journal, Volume 42, Issue 22, 7 June 2021, Pages 2216–2217, https://doi.org/10.1093/eurheartj/ehab166

8.       Forget, P., Khalifa, C., Defour, JP. et al. What is the normal value of the neutrophil-to-lymphocyte ratio?. BMC Res Notes 10, 12 (2017). https://doi.org/10.1186/s13104-016-2335-5

9.       Azab B, Camacho-Rivera M, Taioli E (2014) Average Values and Racial Differences of Neutrophil Lymphocyte Ratio among a Nationally Representative Sample of United States Subjects. PLoS ONE 9(11): e112361.https://doi.org/10.1371/journal.pone.0112361

10.    Jordan P. Iannuzzi, James A. King, Jessica Hope Leong, Joshua Quan, Joseph W. Windsor, Divine Tanyingoh, Stephanie Coward, Nauzer Forbes, Steven J. Heitman, Abdel-Aziz Shaheen, Mark Swain, Michael Buie, Fox E. Underwood, Gilaad G. Kaplan,Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis, Gastroenterology,Volume 162, Issue 1,2022,Pages 122-] 134,ISSN 0016-5085, https://doi.org/10.1053/j.gastro.2021.09.043.

11.    Tan, T.P., Arekapudi, A., Metha, J., Prasad, A. and Venkatraghavan, L. (2015), Neutrophil–lymphocyte ratio. ANZ J Surg, 85: 414-419. https://doi.org/10.1111/ans.13036

12.    Walsh, S.R., Cook, E.J., Goulder, F., Justin, T.A. and Keeling, N.J. (2005), Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer†. J. Surg. Oncol., 91: 181-184. https://doi.org/10.1002/jso.20329

13.    Josee-Lyne Ethier, Danielle N Desautels, Arnoud J Templeton, Amit Oza, Eitan Amir, Stephanie Lheureux, Is the neutrophil-to-lymphocyte ratio prognostic of survival outcomes in gynecologic cancers? A systematic review and meta-analysis,GynecologicOncology,Volume 145, Issue 3,2017,Pages 584-594,ISSN 0090-8258, https://doi.org/10.1016/j.ygyno.2017.02.026.

14.    SerhatTokgoz, Mehmet Kayrak, ZehraAkpinar, Abdullah Seyithanoğlu, FigenGüney, BetigülYürüten, Neutrophil Lymphocyte Ratio as a Predictor of Stroke,Journal of Stroke and Cerebrovascular Diseases,Volume 22, Issue 7,2013,Pages 1169-1174,ISSN 1052-3057, https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.01.011.

15.    Zhiwei Huang, Zhaoyin Fu, Wujun Huang, Kegang Huang, Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: A meta-analysis,The American Journal of Emergency Medicine,Volume 38, Issue 3,2020,Pages 641-647,ISSN 0735-6757, https://doi.org/10.1016/j.ajem.2019.10.023.

16.    Cho, J.H., Kim, T.N. & Kim, S.B. Comparison of clinical course and outcome of acute pancreatitis according to the two main etiologies: alcohol and gallstone. BMC Gastroenterol 15, 87 (2015). https://doi.org/10.1186/s12876-015-0323-1