Clinical value of BISAP score combined with CRP and NLR in evaluating the severity of acute pancreatitis.

In conclusion, BISAP score, CRP, and NLR are independent risk factors for AP and can effectively predict SAP. When combined, they have a more convincing ability to diagnose the severity of AP, and their clinical application value is higher. However, this study was conducted as a retrospective study and requires further confirmation through large sample sizes and prospective research. Additionally, the correlation of BISAP, CRP and NLR with organ failure and infection in patients with SAP is not explored. And the risk factors for prognosis (organ failure, infection and death) in patients with SAP are not analyzed.

Acute pancreatitis (AP) is an inflammatory disease of the pancreas with a rapid and uncontrollable onset, ranging from self-limiting to severe progressive conditions, often accompanied by organ dysfunction and death. [ 1 ] And the incidence rate of AP rang from approximately 13 to 45 cases per 100,000 people per year. [ 2 ] The overall mortality rate is about 5%, with the mortality rate for moderately severe and severe pancreatitis patients accounting for 30% to 40%. [ 3 ] This has posed a serious threat to the health and life of the Chinese population. The update of the 2012 Atlanta Classification criteria for acute pancreatitis has attracted attention. [ 4 ] The most important feature is to recognize that acute pancreatitis is a continuously evolving dynamic disease, and the severity may change during the course of the disease. Therefore, early assessment of the severity of AP is helpful for timely monitoring, diagnosis, and treatment, reducing mortality, and improving prognosis. Currently, there are many clinical scoring systems for acute pancreatitis, such as Ranson score, acute physiology and chronic health evaluation (APACHE II) scoring system, computed tomography severity index, and bedside index for severity in acute pancreatitis (BISAP). [ 5 ] However, they all have certain limitations. These limitations have driven researchers’ interest in developing single biochemical markers as predictors for moderately severe and severe acute pancreatitis (SAP). One such predictor is high-sensitivity C-reactive protein (CRP). [ 6 ] High-sensitivity CRP is an acute-phase reactant that is released into the blood from the liver during the inflammatory response to adjust the inflammation and combat the proteases involved in the inflammatory response. Mayer et al [ 7 ] first reported its potential as a predictor for moderately severe acute pancreatitis (MSAP) and SAP in 1984 and suggested that high-sensitivity CRP had prognostic value for pancreatitis. According to reports, [ 8 ] the neutrophil-lymphocyte ratio (NLR) also has clinical significance in predicting the severity of AP. The BISAP scoring system proposed by Wu et al in 2008 [ 9 ] includes indicators that are relatively easy to obtain after admission, simple to operate, and can be quickly assessed within 24 hours of patient admission. Therefore, this study aims to investigate the combined value of BISAP, CRP, and NLR in assessing the severity of acute pancreatitis in patients.

Conceptualization: Fei Lu, Liugen Gu. Data curation: Fei Lu, Yan Zhang. Formal analysis: Yan Zhang, Jing Yu, Zhenming Ge, Liugen Gu. Investigation: Zhenming Ge. Methodology: Fei Lu, Yan Zhang, Jing Yu. Supervision: Zhenming Ge. Visualization: Jing Yu. Writing – original draft: Fei Lu. Writing – review & editing: Fei Lu, Yan Zhang, Jing Yu, Zhenming Ge, Liugen Gu.

A total of 113 patients diagnosed with acute pancreatitis (AP) were retrospectively collected from the Department of Gastroenterology at the Second Affiliated Hospital of Nantong University between September 2019 and September 2022. Among them, 54 were male and 59 were female, with an average age of 56.42 ± 1.597 years. All patients met the diagnostic criteria outlined in the 2019 WSES Guidelines for the Management of Severe Acute Pancreatitis. [ 10 ] Exclusion criteria included patients with chronic pancreatitis, concurrent infections at the time of admission (e.g., pneumonia), pancreatic tumor patients, those discharged within 24 hours of hospitalization, AP induced by surgery, pregnant women, and patients under 18 years of age. General information such as patient age, gender, symptoms, and vital signs were meticulously recorded for the enrolled cases. Venous blood samples were collected from the patients within 24 hours of admission to measure and analyze white blood cell, neutrophil, lymphocyte counts, and blood urea nitrogen levels. BISAP score and NLR were calculated. Additionally, serum CRP levels within 24 hours and 48 hours after admission, along with imaging data obtained from spiral CT scans within 72 hours, were collected. The AP cases were classified according to 2019 WSES Guidelines for the Management of Severe Acute Pancreatitis. [ 10 ] Cases that showed rapid improvement in the early stages of the disease without organ failure or local or systemic complications were defined as mild acute pancreatitis (MAP). Cases with local or systemic complications but without sustained organ failure were classified as MSAP. Cases with persistent organ failure were classified as SAP. Statistical analysis was performed using IBM SPSS Statistics 21. Normally distributed continuous data were presented as mean ± standard deviation. The chi-square test, corrected chi-square test, or Fisher exact test was used for comparisons between categorical variables, while one-way analysis of variance was used for comparisons among multiple groups. Non-normally distributed data were presented as median (interquartile range), and non-parametric tests were employed. The correlation between variables was assessed using the Spearman test, where 0 < R < 1 indicated a positive correlation, and −1 < R < 0 indicated a negative correlation. Logistic regression analysis was performed with SAP as the dependent variable. Receiver operating characteristic (ROC) curves were plotted, and the maximum Youden index was used to determine the sensitivity and specificity predictive values for the severity of AP under different combination approaches. A significance level of P < .05 was considered statistically significant for all experimental data.

There was no significant difference in age, gender and etiology among the 3 groups of patients. ( P > .05) (Table 1 ). The hospitalization days of MSAP group was longer than that of MAP group (13.38 ± 2.56 vs 6.98 ± 1.26) ( P < .05), and SAP group was longer than that of MSAP group (22.33 ± 2.64 vs 13.38 ± 2.56) ( P < .05). General information. MAP = mild acute pancreatitis, MSAP = moderately severe acute pancreatitis, SAP = severe acute pancreatitis group. A total of 51 MAP, 32 MSAP and 30 SAP were recruited in our study for testing. The BISAP score of MSAP group was higher than that of MAP group (1.688 ± 0.1225 vs 0.9608 ± 0.1119) ( P < .05), and SAP group was higher than that of MSAP group (2.6 ± 0.1135 vs 1.688 ± 0.1225) ( P < .05). The CRP concentration of MSAP group was higher than that of MAP group (142.9 ± 11.44mg/L vs 74.77 ± 8.336mg/L) ( P < .05), and SAP group was higher than that of MSAP group (187.6 ± 13.04 vs 142.9 ± 11.44mg/L) ( P < .05). The NLR of MSAP group was higher than that of MAP group (13.69 ± 1.023 vs 8.063 ± 0.7781) ( P < .05), and SAP group was higher than that of MSAP group (18.06 ± 1.685 vs 13.69 ± 1.023) ( P < .05) (Table 2 ). Comparison of BISAP score, CRP and NLR MAP/MSAP group and SAP group. Compared with the MAP group, P < 0.05, Compared with MSAP group, P < .05. BISAP = bedside index for severity in acute pancreatitis, CRP = C-reactive protein, MAP = mild acute pancreatitis, MSAP = moderately severe acute pancreatitis, NLR = neutrophil-to-lymphocyte ratio, SAP = severe acute pancreatitis group. Spearman correlation analysis revealed that BISAP score had positive correlation with CRP and NLR, with the correlation coefficient (R) values of 0.5062 and 0.5247, respectively (Fig. 1 A and B). Correlation of bedside index for severity in acute pancreatitis (BISAP), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) among the 3 groups. Logistic regression analysis with SAP as dependent variable and BISAP, CRP and NLR as independent variables showed that CRP and BISAP score increased, the probability of SAP increased ( P < .05) (Table 3 ). The MSAP group and MAP group were combined into non SAP group, and the ROC curves of each index predicting SAP and non SAP were drawn. The ROC curve indicated that the area under the curve (AUCs) for evaluating SAP with BISAP score, CRP, and NLR were 0.885, 0.814, and 0.714, respectively. The combined AUC for all 3 parameters was 0.953 (Fig. 2 ). The sensitivity and specificity of BISAP score, CRP and NLR and different combination methods were determined according to the maximum Youden index. The results showed that the sensitivity (86.7%) and specificity (100%) of CRP, NLR combined with BISAP score were the highest. Logistic regression analysis of influencing factors of SAP. BISAP = bedside index for severity in acute pancreatitis, CRP = C-reactive protein, NLR = neutrophil-to-lymphocyte ratio, SAP = severe acute pancreatitis group. Diagonal segments generated by the knot.

Approximately 80% of patients experience mild pancreatic injury, with the disease usually resolving within 1 to 2 weeks and requiring only brief hospitalization. However, around 20% of patients progress to severe AP. While most of the severely affected patients can be cured without complications, 25% of patients admitted to the ICU for 2 weeks still experience severe complications or even death after treatment. [ 11 ] Therefore, early assessment of AP is essential for identifying high-risk patients, optimizing treatment plans, and reducing mortality. Since 1991, numerous medical experts both domestically and internationally have revised the definition and classification criteria for AP based on their accumulated clinical experience and in-depth research on the pathogenesis of pancreatitis, providing guidance for clinical practice. Currently, many commonly used AP scoring systems in clinical practice have their limitations. The Ranson score suffers from incomplete data collection, which reduces the maximum score obtained at a given time and consequently decreases its sensitivity. The APACHE II score can objectively predict disease severity, but its complexity makes it impractical for routine use. BISAP has similar accuracy to APACHE II, [ 12 ] but it is relatively simplified. However, its main drawback lies in its emphasis on static measurements, neglecting temporal changes. Therefore, using BISAP score alone no longer offers an advantage. Thus, we attempted to combine BISAP score with clinical biochemical indicators to predict early AP severity and obtain higher predictive value. In our study, the BISAP score in the SAP group was significantly higher than that in the MSAP group and MAP group, consistent with the findings of many other studies. [ 13 ] The ROC curve demonstrated an AUC of 0.885 for the BISAP score, indicating its valuable predictive value for the severity and prognosis of early-stage AP. The pathological and physiological process of acute pancreatitis (AP) involves excessive release of inflammatory cytokines and mediators, leading to severe local tissue damage and systemic inflammation. [ 14 ] CRP and NLR are likely to be involved in the occurrence of AP. CRP is an acute nonspecific reactant and an important indicator of the degree of inflammation. A study [ 15 ] showed that the measurement of inflammatory cytokines at admission and CRP on the third day of admission can predict systemic complications in AP patients. The predictive value of NLR has been reported in colorectal cancer, lung cancer, and pancreatic cancer, and an increasing number of studies have indicated that NLR is not only a cancer-specific prognostic factor but also a prognostic factor for systemic inflammatory diseases (such as sepsis) and acute kidney injury. [ 16 ] Neutrophils, as crucial initiators of tissue necrosis cascade reactions, significantly activate in large numbers in the early stages of AP, leading to their accumulation at the tissue site and excessive activation in the circulation, causing microvascular damage, promoting the release of inflammatory mediators, and exacerbating systemic inflammatory response. [ 17 ] On the other hand, lymphocytes play a key role in regulating and alleviating nonspecific inflammatory responses in AP. Reduced lymphocyte counts are mainly associated with apoptosis, functional impairment, and weakened humoral immunity. [ 18 ] In our study, CRP and NLR were significantly higher in the severe acute pancreatitis (SAP) group than in the MAP group. Logistic regression analysis showed that CRP and BISAP score increased, the probability of SAP increased. Previous research [ 19 ] has confirmed that BISAP score is a useful tool for assessing the severity and prognosis of AP. In our study, Pearson correlation coefficient showed a positive correlation between CRP, NLR, and BISAP score, suggesting that CRP and NLR have the potential to be useful indicators for evaluating SAP. The ROC curve indicated that the AUCs for predicting SAP with BISAP score, CRP, and NLR were 0.885, 0.814, and 0.714, respectively. The combined AUC for all 3 parameters was 0.953. The sensitivity (86.7%) and specificity (100%) of CRP, NLR combined with BISAP score were the highest, demonstrating that BISAP, CRP combined NLR significantly improve the accuracy of predicting SAP.