Xu MS, Xu JL, Gao X, Mo SJ, Xing JY, Liu JH, Tian YZ, Fu XF. Clinical study of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in hypertriglyceridemia-induced acute pancreatitis and acute biliary pancreatitis with persistent organ failure. World J Gastrointest Surg 2024; 16(6): 1647-1659 [PMID: 38983313 DOI: 10.4240/wjgs.v16.i6.1647]
Corresponding Author of This Article
Xi-Feng Fu, MMed, Chief Physician, The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, No. 88 Longcheng Street, Taiyuan 030032, Shanxi Province, China. fxfyisheng@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Surg. Jun 27, 2024; 16(6): 1647-1659 Published online Jun 27, 2024. doi: 10.4240/wjgs.v16.i6.1647
Clinical study of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in hypertriglyceridemia-induced acute pancreatitis and acute biliary pancreatitis with persistent organ failure
Mu-Sen Xu, Jia-Le Xu, Shao-Jian Mo, Jia-Yu Xing, Jia-Hang Liu, Yan-Zhang Tian, Xi-Feng Fu, The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
Xin Gao, Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan 030032, Shanxi Province, China
Author contributions: Xu MS and Mo SJ designed the study; Xu MS, Xu JL, and Gao X collected data; Xu JL and Gao X analyzed and interpreted the results; Xu MS and Mo SJ drafted and revised the manuscript; all authors have approved the final manuscript.
Supported byShanxi Province “136” Revitalization Medical Project Construction Funds, No. 2019XY004.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Shanxi Bethune Hospital (approval No. YXLL-2023-237)
Informed consent statement: Informed consent was voluntarily signed by the patients when they received treatment, and the informed consent forms were stored in Hospital Information System.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The data that support the findings of this study are available on request from the corresponding author, The data are not publicly available due to privacy or ethical restrictions.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xi-Feng Fu, MMed, Chief Physician, The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, No. 88 Longcheng Street, Taiyuan 030032, Shanxi Province, China. fxfyisheng@163.com
Received: February 3, 2024 Revised: March 10, 2024 Accepted: May 14, 2024 Published online: June 27, 2024 Processing time: 147 Days and 21.3 Hours
Abstract
BACKGROUND
The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammatory indicators that can be used to predict the severity and prognosis of various diseases. We categorize acute pancreatitis by etiology into acute biliary pancreatitis (ABP) and hypertriglyceridemia-induced acute pancreatitis (HTGP).
AIM
To investigate the clinical significance of NLR and PLR in assessing persistent organ failure (POF) in HTGP and ABP.
METHODS
A total of 1450 patients diagnosed with acute pancreatitis (AP) for the first time at Shanxi Bethune Hospital between January 2012 and January 2023 were enrolled. The patients were categorized into two groups according to the etiology of AP: ABP in 530 patients and HTGP in 241 patients. We collected and compared the clinical data of the patients, including NLR, PLR, and AP prognostic scoring systems, within 48 h of hospital admission.
RESULTS
The NLR (9.1 vs 6.9, P < 0.001) and PLR (203.1 vs 160.5, P < 0.001) were significantly higher in the ABP group than in the HTGP group. In the HTGP group, both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score ≥ 3. Likewise, in the ABP group, NLR and PLR were significantly elevated in patients with severe AP, modified computed tomography severity index score ≥ 4, Japanese Severity Score ≥ 3, and modified Marshall score ≥ 2. Moreover, NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP groups.
CONCLUSION
NLR and PLR vary between ABP and HTGP, are strongly associated with AP prognostic scoring systems, and have predictive potential for the occurrence of POF in both ABP and HTGP.
Core Tip: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammatory indicators that can effectively predict disease severity and prognosis. In this study, starting from the two common causes of acute pancreatitis (AP), the difference between the NLR and PLR in hypertriglyceridemia-induced acute pancreatitis (HTGP) and acute biliary pancreatitis (ABP) was explored retrospectively, and the predictive value of the NLR and PLR for persistent organ failure in HTGP and ABP were determined. To help clinicians maintain a high degree of vigilance in the early stages of AP, timely treatment interventions are needed to reduce the mortality of AP.
Citation: Xu MS, Xu JL, Gao X, Mo SJ, Xing JY, Liu JH, Tian YZ, Fu XF. Clinical study of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in hypertriglyceridemia-induced acute pancreatitis and acute biliary pancreatitis with persistent organ failure. World J Gastrointest Surg 2024; 16(6): 1647-1659
Acute pancreatitis (AP) is a common exocrine inflammatory disorder[1] characterized by the activation of cytokine cascades, leading to systemic inflammation[2], severe abdominal pain, and multiorgan dysfunction[3]. Approximately one-third of patients may progress to severe pancreatitis[4], ultimately leading to pancreatic necrosis and persistent organ failure (POF), with a mortality rate of 1%-5%.
In European and North American countries, the main etiological factors of AP are gallstones (50%) and alcohol consumption (25%)[5], with hypertriglyceridemia (HTG) being the third leading cause, accounting for 10% of all pancreatitis episodes. However, epidemiological studies in China have shown that gallstones account for 63.0% of AP cases, hyperlipidemia for 8.5%, and alcohol-induced cases 7.4%[6]. With changes in the dietary habits of the human population, the proportion of hyperlipidemia-related cases is continuously increasing. Approximately, 15%-20% of patients with severe HTG (> 11.0 mmol/L) are estimated to develop AP, leading to persistent multiorgan failure[7]. The inflammatory mechanisms underlying AP remain unclear[8], and there is significant clinical heterogeneity. Currently, no specific drugs are available to alter the disease[9]. Although many patients with AP may appear relatively stable upon admission, their ultimate prognosis often falls short of expectations as the disease progresses. Therefore, a reliable and objective assessment method is required to assist in the clinical prognostic evaluation of AP.
Several AP scoring systems are currently available to assist clinicians in predicting the prognosis of AP patients. Common scores include the Bedside Index for Severity in Acute Pancreatitis (BISAP) score, modified computed tomography severity index (MCTSI), Modified Marshall score, Sequential Organ Failure Assessment (SOFA) score, and Japanese Severity Score (JSS). However, these scoring systems are time consuming and require extensive clinical data in combination with imaging[10]. In situations with limited resources, it may not be feasible to obtain all the parameters of these scoring systems promptly, leading to difficulties in the early assessment of AP severity and impacting patient management and prognosis. Therefore, there has been an ongoing search for a simple, practical, quantifiable, easily collectible, and readily available indicator for predicting AP severity[11]. Serum biomarkers such as white blood cell count, neutrophil count, lymphocyte count, platelet count, and C-reactive protein[12] have been identified as having good value in predicting the prognosis and severity of AP[13].
Recently, novel serum biomarkers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have shown high value in predicting the severity of various diseases, including inflammation and tumors[14]. Studies have demonstrated that an elevated NLR within 48 h of admission is significantly associated with severe AP (SAP) and serves as an independent prognostic indicator for AP[15]; PLR has also been identified as an auxiliary marker for predicting the severity of AP[11]. Although these studies have explored the prognostic value of NLR and PLR in AP, there is a lack of comparative analyses regarding their prognostic significance in patients with AP of different etiologies. In this study, we aimed to evaluate and compare the prognostic values of NLR and PLR in HTG-induced acute pancreatitis (HTGP) and acute biliary pancreatitis (ABP) in terms of the development of POF. Additionally, we compared their effectiveness and practicality with those of the existing scoring systems.
MATERIALS AND METHODS
Patient characteristics
We retrospectively analyzed 1450 patients diagnosed with AP for the first time at Shanxi Bethune Hospital between January 2012 and January 2023. After strict selection, 771 patients were included. This study was retrospective, and all data were derived from the Hospital Information System (HIS). Informed consent was obtained from each patient upon admission, with informed consent forms stored in the HIS. This study strictly adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Shanxi Bethune Hospital (ethics approval No: YXLL-2023-237).
The diagnosis of AP requires two of the following three criteria: (1) Typical abdominal pain; (2) Serum amylase or lipase elevation ≥ 3 times the upper limit of normal; and (3) Characteristic findings of AP on contrast-enhanced computed tomography (CT), magnetic resonance imaging, or abdominal ultrasonography[16].
The diagnostic criteria for ABP are based on the diagnosis of AP, where imaging can confirm impaired emptying of the bile and pancreatic ducts at the ampulla of Vater because of causes such as gallbladder stones, common bile duct stones, and biliary tract infections[17]. The diagnostic criteria for HTGP are as follows: in the presence of an AP diagnosis, if the serum triglyceride (TG) level is ≥ 11.3 mmol/L, or when the TG level is between 5.65 and 11.3 mmol/L, if other causes of AP are excluded, a high suspicion of HTGP should be considered[18].
Patients were stratified based on disease severity using the revised Atlanta classification (RAC) as follows: (1) Mild acute pancreatitis (MAP), no organ failure or local or systemic complications; (2) Moderate to severe acute pancreatitis, transient organ failure (resolution within 48 h) or local complications; and (3) SAP: POF (lasting > 48 h)[2]. The diagnosis of organ failure (OF) was based on the Modified Marshall Scoring System, with any organ score ≥ 2 defining the presence of OF. OF lasting more than 48 h was defined as POF[19]. During the study period, 1450 patients were diagnosed with AP (Figure 1). Patients with etiologies other than gallstone or HTG were excluded. All patients were followed-up until discharge or death.
Inclusion criteria: (1) Meet the diagnostic criteria for AP, HTGP, and ABP; (2) Age ≥ 18 years; (3) Hospitalized within 48 h after onset of symptoms; (4) Patients admitted to Shanxi Bethune Hospital for the first time with a diagnosis of AP; and (5) Complete clinical data.
Exclusion criteria: (1) Incomplete clinical data or missing medical records; (2) Chronic pancreatitis, pancreatitis of other types such as alcohol-induced, trauma-induced, or pregnancy-related; (3) Patients with history of tumors, infections, immune system disorders, or hematological diseases; and (4) Use of antibiotics or corticosteroids within the past week.
Data collection
General Information: sex, age, height (cm), weight (kg), body mass index (BMI), underlying diseases (hypertension, diabetes, etc.), and presence or absence of POF. Laboratory and imaging indicators within 24 h of admission included liver and kidney function, complete blood count, coagulation function, arterial blood gas analysis, and abdominal CT.
Statistical analysis
The statistical software SPSS (version 26.0) was used for the data analysis. Normally distributed continuous variables are expressed as mean ± SD. The median (interquartile range, 25th-75th percentile) was used for variables that did not follow a normal distribution. Differences between the two groups were analyzed using Student’s t-test. Binary logistic regression analysis was used to identify risk factors. The diagnostic performance of the indicators was evaluated using receiver operating characteristic curves, with a significance level of P < 0.05 indicating statistically significant differences.
RESULTS
Patient characteristics
Comparison of the baseline characteristics of patients: 466 male and 305 female patients with AP. In total, 128 patients had diabetes, 190 had hypertension, and 188 had hyperlipidemia. According to the Modified Marshall Scoring criteria, among patients with AP, 234 had POF and 537 did not have POF. The ABP group had a higher average age, lower BMI, lower male-to-female ratio, and lower proportion of smokers. The HTGP group had higher white blood cell, lymphocyte, and platelet counts. However, NLR (9.1 vs 6.9, P < 0.001) and PLR (203.1 vs 160.5, P < 0.001) were significantly higher in the ABP group than in the HTGP group. In terms of liver function indicators, the HTGP group had higher levels of cholesterol and TGs, whereas the other indicators were lower than those in the ABP group. The ABP group also had a higher proportion of patients with hypertension. The average length of hospital stay was shorter in the HTGP group than in the ABP group; however, the SAP incidence rate was higher in the HTGP group than in the ABP group. There were no significant differences between the two groups in terms of intensive care unit (ICU) admission rate, systemic inflammatory response syndrome (SIRS), POF incidence rate, and mortality rate. In the AP scoring system, there were no significant differences in the SOFA scores. The MCTSI score and JSS were higher in the HTGP group than in the ABP group, whereas the Modified Marshall and BISAP scores were significantly higher in the ABP group (Table 1).
Group analysis of NLR and PLR about the previous AP scoring system
We conducted a group analysis based on the etiology of AP. Regarding HTGP, patients with severe pancreatitis (defined according to the RAC) and a SOFA score ≥ 3 (P < 0.05) exhibited significantly higher PLR and NLR (Table 2).
Table 2 Correlation analysis of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio with the acute pancreatitis Scoring System in hypertriglyceridemia-induced acute pancreatitis.
Parameters
PLR
P value
NLR
P value
Atlanta classification
0.000
0.005
Mild/moderate
152.1 (110.8; 198.0)
6.3 (3.5; 10.2)
Severe
188.2 (137.9; 265.6)
7.9 (5.5; 12.6)
MCTSI
0.087
0.235
< 4
150.6 (113.4; 197.4)
6.1 (3.4; 10.1)
≥ 4
161.7 (119.1; 240.6)
7.0 (4.4; 11.2)
JSS
0.754
0.815
< 3
159.0 (119.9; 228.0)
6.9 (3.9; 11.2)
≥ 3
161.2 (108.2; 257.6)
7.0 (5.0; 10.2)
BISAP
0.384
0.395
< 3
159.1 (119.0; 228.4)
6.9 (4.0; 10.9)
≥ 3
171.6 (136.7; 244.4)
9.1 (5.8; 12.9)
Modified Marshall
0.167
0.813
< 2
156.2 (113.4; 214.1)
6.8 (3.8; 11.6)
≥ 2
165.1 (132.0; 239.1)
7.0 (4.9; 10.3)
SOFA
0.011
0.005
< 3
155.6 (113.2; 214.9)
6.4 (3.6; 10.1)
≥ 3
175.0 (136.0; 259.6)
8.0 (5.9; 12.8)
The relationship between NLR, PLR, and the AP scoring system was more pronounced in ABP. In ABP, patients with severe pancreatitis (defined according to the RAC), MCTSI score ≥ 4, JSS ≥ 3, and Modified Marshall score ≥ 2 exhibited significantly higher PLR and NLR. However, when the BISAP score was ≥ 3 (15.6, P = 0.002) and SOFA score ≥ 3 (12.4, P < 0.001), only NLR showed a significant increase, whereas PLR did not show statistical significance (Table 3).
Table 3 Correlation Analysis of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio with the acute pancreatitis Scoring System in acute biliary pancreatitis.
Parameters
PLR
P value
NLR
P value
Atlanta classification
0.002
0.000
Mild/moderate
194.0 (136.2; 286.2)
8.1 (4.3; 13.8)
Severe
239.1 (171.0; 358.9)
16.0 (8.9; 21.8)
MCTSI
0.021
0.000
< 4
190.8 (135.4; 268.6)
7.4 (4.0; 12.8)
≥ 4
212.7 (145.3; 322.9)
11.2 (6.0; 17.6)
JSS
0.006
0.000
< 3
194.5 (139.2; 287.6)
8.2 (4.3; 14.2)
≥ 3
250.6 (150.7; 359.1)
16.5 (8.7; 22.9)
BISAP
0.921
0.002
< 3
203.8 (141.9; 295.9)
8.9 (4.5; 15.7)
≥ 3
192.9 (130.4; 329.9)
15.6 (11.2; 20.4)
Modified Marshall
0.015
0.000
< 2
181.2 (134.0; 272.3)
6.0 (3.5; 12.0)
≥ 2
217.2 (145.2; 314.6)
11.3 (6.2; 18.3)
SOFA
0.555
0.000
< 3
198.5 (140.4; 296.4)
8.2 (4.1; 14.5)
≥ 3
212.2 (142.1; 311.3)
12.4 (7.3; 19.3)
Comparison of the predictive value of NLR, PLR, and the AP scoring system for POF in HTGP
We calculated the area under the curve (AUC) of the NLR and PLR to predict the occurrence of POF in HTGP patients and compared them with the previous AP scoring system (Figure 2A). In HTGP patients, neither NLR nor PLR showed a significant advantage in predicting POF (NLR-AUC 0.619, 95%CI: 0.55-0.69; PLR-AUC 0.622, 95%CI: 0.55-0.70). In contrast, the SOFA and Modified Marshall scores had higher predictive values, with AUCs of 0.827 and 0.772, sensitivities of 71.3% and 66.3%, and specificities of 82.0% and 79.5%, respectively (Table 4).
Figure 2 Receiver operating characteristic curve.
A: Receiver operating characteristic (ROC) curve for the prediction of persistent organ failure (POF) in hypertriglyceridemia-induced acute pancreatitis by neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the acute pancreatitis (AP) Scoring System; B: ROC curve for the prediction of POF in acute biliary pancreatitis by NLR, PLR, and the AP Scoring System. ROC: Receiver operating characteristic; MCTSI: Modified computed tomography severity index; JSS: Japanese Severity Score; BISAP: Bedside Index for Severity in Acute Pancreatitis; SOFA: Sequential Organ Failure Assessment; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio.
Table 4 Predictive performance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the acute pancreatitis Scoring System for the occurrence of persistent organ failure in hypertriglyceridemia-induced acute pancreatitis.
Parameters
AUC
95%CI
Sensitivity
Specificity
P value
Lower
Upper
MCTSI
0.718
0.649
0.786
0.650
0.733
< 0.001
JSS
0.703
0.631
0.775
0.663
0.720
< 0.001
BISAP
0.705
0.634
0.775
0.725
0.652
< 0.001
Modified Marshall
0.772
0.708
0.835
0.663
0.795
< 0.001
SOFA
0.827
0.772
0.882
0.713
0.820
< 0.001
PLR
0.622
0.546
0.699
0.413
0.826
0.002
NLR
0.619
0.546
0.693
0.800
0.720
0.003
Comparison of the predictive value of NLR, PLR, and the AP scoring system for POF in ABP
Similarly, we calculated the AUC of NLR and PLR to predict the occurrence of POF in ABP patients and compared them with the previous AP scoring system (Figure 2B). In ABP patients, NLR and PLR also did not demonstrate significant advantages in predictive value (NLR-AUC 0.668, 95%CI: 0.62-0.72; PLR-AUC 0.569, 95%CI: 0.52-0.62). However, the Modified Marshall score and JSS showed higher predictive values for biliary AP, with AUCs of 0.761 and 0.760, sensitivities of 67.5% and 59.1%, and specificities of 70.5% and 78.2%, respectively (Table 5).
Table 5 Predictive performance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the acute pancreatitis Scoring System for the occurrence of persistent organ failure in acute biliary pancreatitis.
Parameters
AUC
95%CI
Sensitivity
Specificity
P value
Lower
Upper
MCTSI
0.573
0.517
0.629
0.409
0.729
0.008
JSS
0.760
0.715
0.805
0.591
0.782
< 0.001
BISAP
0.694
0.645
0.743
0.448
0.827
< 0.001
Modified Marshall
0.761
0.717
0.804
0.675
0.705
< 0.001
SOFA
0.746
0.703
0.789
0.942
0.465
< 0.001
PLR
0.569
0.516
0.621
0.727
0.418
0.013
NLR
0.668
0.618
0.717
0.532
0.761
< 0.001
DISCUSSION
AP is characterized by the activation of innate and adaptive immune responses, resulting in inflammation. AP manifests as an acute abdomen, primarily characterized by local pancreatic inflammation caused by the abnormal activation of pancreatic enzymes, leading to digestive effects on the pancreas and surrounding organs. An excessive inflammatory response can result in the transfer of a large number of inflammatory factors to the pancreas, causing pancreatic damage, and ultimately affecting multiple organs and systems throughout the body, leading to SAP[20]. The mortality rate of SAP is as high as 15%-30%, while that of MAP is only 0-1%. Furthermore, the clinical presentation of AP is unreliable and lacks specificity, with a sensitivity of less than 40% for predicting adverse outcomes[21].
Therefore, early identification, accurate staging, and timely treatment of SAP are crucial for reducing the incidence and mortality rates of AP[22]. Existing research has demonstrated that early prediction of AP severity allows for effective intervention, thereby improving patient outcomes[23].
Among the etiological factors of AP, gallstones and alcohol consumption are the predominant causes[24], and the incidence of HTG has been increasing annually. Currently, HTG is the second most common etiology of AP in Chinese patients[25]. Compared to AP caused by other etiologies, HTGP is characterized by a tendency to develop severe disease and frequent recurrence, which presents unique challenges in its diagnosis and treatment. The exact mechanisms underlying the development of HTGP are not yet fully understood; however, the prevailing theory suggests that chylomicrons play a central role. Chylomicrons are lipid-protein particles rich in TGs synthesized from dietary lipids within intestinal cells. They consist of a TG-rich core and carry esterified cholesterol and phospholipids[26]. When serum TG levels exceed 10 mmol/L, chylomicrons appear in the bloodstream[27], which can impede circulation in the capillary bed, leading to ischemia. In addition, chylomicrons increase plasma viscosity, causing capillary blockage, ischemia, and cellular acidosis. Moreover, chylomicrons undergo hydrolysis within the pancreatic vascular bed, releasing free fatty acids (FFA) that exceed the binding capacity of plasma albumin. The unbound FFA self-aggregate into micellar structures with detergent-like properties[28]. These toxic structures can damage the platelets, endothelial cells, and acinar cells, leading to pancreatic cell ischemia and acidosis. Acidosis, in turn, enhances the toxicity of FFA by activating pancreatic proteases, ultimately triggering AP[29]. A prospective study conducted by Nawaz et al[30] demonstrated that HTGP is an independent risk factor for POF. Compared with AP caused by other etiologies, HTGP has been shown to have a higher severity and incidence of complications[31,32]. This is in line with the conclusions of this study, which demonstrated that HTGP was more severe than ABP, but there was no significant difference in the rates of SIRS or POF between the two groups.
ABP is caused by various factors such as gallbladder stones, common bile duct stones, biliary tract infection, abnormal sphincter of Oddi spasm, and stenosis, which impair the emptying of the biliary and pancreatic ducts and cause abnormal biliary pressure. This results in bile reflux into the pancreatic duct, obstruction of pancreatic fluid drainage, and abnormal activation of pancreatic enzymes[33]. The mechanisms underlying the development of HTGP and ABP are completely different. However, both eventually lead to pancreatic cell injury and release of inflammatory mediators. Therefore, the use of inflammatory markers to assess the prognosis of pancreatitis caused by various mechanisms is particularly important.
Currently, there is increasing evidence supporting a close association between inflammatory mediators and the pathogenesis of AP[34], Inflammatory signals released by pancreatic acinar cells can mediate the recruitment and activation of circulating inflammatory cells[35]. Ultimately, excessive activation of inflammatory mediators can trigger a systemic inflammatory response, leading to SAP.
NLR is a systemic inflammation marker based on the complete blood cell count and was initially proposed as a means of evaluating systemic inflammation and stress response in critically ill patients[36]. Generally, the neutrophil count in blood increases with the progression of inflammatory diseases. However, in certain conditions, such as cachexia, "false-negative" results may occur. The lymphocyte count also reflects the patient's immune status, which tends to decrease with the progression of inflammatory diseases. However, lymphocyte count often decreases significantly only in the later stages of the disease, making it inadequate to reflect disease progression[37]. Therefore, NLR is considered more reliable than either neutrophil or lymphocyte count alone in predicting patient prognosis and survival rates[38]. Generally, NLR increases with the occurrence of systemic inflammatory diseases and severity of inflammation, which is consistent with the development of certain diseases[39]. Additionally, the measurement of NLR and PLR is simple, rapid, and cost-effective and does not cause discomfort to patients because it only requires a peripheral blood sample. Numerous studies have demonstrated that a high NLR can serve as an independent prognostic factor for various diseases, including liver cirrhosis[40], acute respiratory distress syndrome[41], and others.
The PLR has also been recognized as an inflammatory marker that can better predict clinical outcomes in patients with systemic inflammation than individual platelet or lymphocyte counts. Platelets play a crucial role in the interactions between inflammation and microvascular dysfunction. Under high levels of pro-inflammatory cytokines and in the presence of cellular debris and viral proteins, platelets can be directly activated, leading to increased aggregation, clotting, or degradation. This can result in a decreased platelet counts[42]. Therefore, PLR tends to decrease during the early stages of disease progression. However, in patients with severe conditions, the PLR significantly increases, which is associated with a substantial decrease in the lymphocyte count[43]. Changes in the PLR were positively correlated with other markers of systemic inflammation, especially the NLR. In the past decade, the PLR has emerged as a laboratory marker for predicting various conditions such as tumors, thrombosis, and metabolic diseases. These include peripheral arterial occlusive disease[44], colorectal tumors[45], acute coronary syndrome[46], acute pulmonary embolism[47], and others.
Azab et al[48] was the first to apply the NLR in patients with AP. They found that NLR was a better predictor of ICU admission rates and prolonged hospital stays in AP patients. However, this study did not assess the impact of NLR on organ failure. Suppiah et al[15] found a significant correlation between increased NLR within the first 48 h of hospitalization and SAP. They identified NLR as an independent prognostic indicator for SAP. However, the study had a small sample size (n = 146), with only 22 patients diagnosed with SAP. Zhang et al[14] indicated that an elevated NLR in the Chinese population was associated with POF, prolonged ICU stay, and increased in-hospital mortality. However, few studies have compared AP according to etiology. Silva-Vaz et al[49] found that the NLR had the best predictive value for severity in the ABP group. Huang et al[50] found that the NLR was only predictive of SAP in the HTGP group; however, this study had a small sample size of 23 patients in the HTGP group with SAP. Therefore, in this study, we excluded pancreatitis caused by factors other than biliary or HTG etiology. After grouping AP based on etiology, our findings were similar to those of Silva-Vaz et al[49], with higher values of NLR and PLR observed in the ABP group. NLR and PLR were both independent predictors of POF in ABP and HTGP. However, NLR and PLR did not demonstrate significant differences between these two types of pancreatitis, suggesting that although ABP and HTGP have different pathogenic mechanisms, the changes in routine blood tests have a similar effect on the progression of AP complicated by POF. In our study findings, compared to the HTGP group, patients in the ABP group exhibited higher levels of liver function indicators such as aspartate aminotransferase, alanine aminotransferase, and total bilirubin. This can be attributed to the presence of biliary obstruction, which leads to increased biliary pressure in the ABP, resulting in the accumulation of bilirubin and bile acids in the liver. The toxic effects of these substances can cause metabolic disturbances and even hepatocellular degeneration and necrosis. The average length of hospital stay was shorter in the HTGP group than in the ABP group. This is because patients in the ABP group often require surgical intervention to relieve biliary obstruction, in addition to general supportive and medical treatments, which, to some extent, prolong their hospital stay[51]. In this study, the incidence of SAP was higher in the HTGP group than in the ABP group. This finding is consistent with that of Anderson et al[31]. Furthermore, animal studies have shown that experimental mouse models of HTGP exhibit higher levels of pancreatic lipase activity and greater histological damage to the pancreatic tissue, making them more prone to progressing to SAP[52].
However, there were no significant differences between the two groups in terms of ICU admission rates, SIRS, POF incidence, and mortality rates. This may be attributed to the early and timely assessment, standardized treatment, and combined interventions implemented in our hospital, which prevented the further progression of AP to some extent. These findings highlight the crucial role of early assessment in guiding AP progression and intervention.
Additionally, the patients in the HTGP group had a younger average age, were predominantly male, and had a higher BMI than those in the ABP group. This is consistent with the clinical characteristics evaluated in international prospective cohorts that assessed HTGP[53]. No significant differences in the SOFA scores between the HTGP and ABP groups in the AP scoring system was observed. The MCTSI scores and JSS were higher in the HTGP group than in the ABP group. This can be attributed to the fact that both the MCTSI score and JSS involve assessment of the extent of pancreatic morphological changes, and studies have indicated a close relationship between pancreatic adipocytes and TGs. Pancreatic adipocytes are specialized cells found within pancreatic tissue and are primarily responsible for synthesizing and storing TGs to regulate pancreatic lipid metabolism. Under normal conditions, TGs are stored within pancreatic adipocytes and released when needed for energy and other biological processes. However, under certain circumstances, such as pancreatitis or pancreatic dysfunction, pancreatic adipocytes may be affected, leading to abnormal TG synthesis and metabolism. Therefore, when AP is caused by TGs, there is an increase in the volume of pancreatic adipocytes, which contributes to extensive pancreatic tissue necrosis[54]. Modified Marshall scores were higher in the ABP group than in the HTGP group. Currently, no literature explicitly indicates a higher incidence of organ failure in patients with ABP. However, recent studies have shown that in the HTGP group, there is a significant increase in the risk of organ failure only in males (excluding females), which to some extent lowers the overall incidence of organ failure in the HTGP group[55]. BISAP scores were significantly higher in the ABP group than in the HTGP group. This may be attributed to the fact that one of the scoring criteria in the BISAP is age > 60 years. In this study, there were 225 patients in the ABP group aged > 60 years, accounting for 42.5% of the total, whereas in the HTGP group, there was only one patient aged > 60 years, accounting for 0.4% of the total.
An et al[56] confirmed that inflammatory cytokines play a major role in the early stages of HTGP, which is consistent with the results of this study. The data collected in this group were laboratory test results within 48 h of admission, representing the early stage of AP progression. The HTGP group of inflammatory markers (white blood cell, lymphocyte, and platelet counts) were higher in the HTGP group than in the ABP group. Previous studies have indicated a positive correlation between the NLR and PLR and the severity of AP[57,58]. This finding was confirmed only in the ABP group regarding NLR. This inconsistency with previous studies may be attributed to the lack of etiological stratification of AP, as the pathophysiological mechanisms of AP may differ according to the underlying causes.
However, this study had several limitations. First, this was a single-center study, and further validation in multiple large-scale pancreatitis centers is required. Second, because of the different clinical manifestations of AP patients upon admission, most patients were not tested for C-reactive protein, procalcitonin, and cytokines after admission. Therefore, we did not compare NLR and PLR with other biomarkers such as C-reactive protein, procalcitonin, and cytokines. Third, because our dataset lacked sufficient information to assess all the potential confounding factors, we included only one clinical outcome (POF) in the analysis. Moreover, we did not report changes in NLR or PLR during the treatment course, which could potentially provide a better prognostic assessment of AP.
Despite these limitations, this study has several merits. We collected cases of AP from our hospital over the past decade, starting from the etiological grouping of AP, performed an etiological grouping of AP, and explored the differences in NLR and PLR between the two subgroups (ABP and HTGP). Furthermore, all laboratory parameters were derived from blood samples obtained before treatment initiation, minimizing the possible influence of fluid resuscitation and medication on white blood cell, lymphocyte, and platelet counts.
CONCLUSION
The NLR and PLR differed between ABP and HTGP. In patients with ABP, both the NLR and PLR values were higher than those in patients with HTGP. NLR and PLR had predictive value for POF in both ABP and HTGP.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country/Territory of origin: China
Peer-review report’s classification
Scientific Quality: Grade C, Grade C
Novelty: Grade B, Grade C
Creativity or Innovation: Grade B, Grade C
Scientific Significance: Grade B, Grade C
P-Reviewer: Aseni P, Italy S-Editor: Yan JP L-Editor: A P-Editor: Che XX
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