The role of biomarkers in prediction of the severity and prognosis of acute pancreatitis: a retrospective assessment

Authors

Abstract

Aim
Determining the severity of acute pancreatitis (AP) is very important in terms of early recognition of sepsis, local/systemic complications and potential risk of death. In our study, we aimed to examine the effectiveness of biomarkers that we can use to reduce morbidity and mortality in AP patients.
Methods
Data of 482 AP patients followed up at Mehmet Akif Inan Training and Research Hospital between January 2020 and July 2022 were analyzed. Age, gender, comorbidities, clinical history, laboratory/imaging findings and hospital stay were evaluated. Our study was carried out with the permission of the ethics committee numbered HRU/21.13.07 obtained from Harran University.
Results
Among AP patients, 471 (98.1%) were diagnosed with biliary pancreatitis, 11 (2.2%) with hyperlipidemia and non-biliary pancreatitis due to chronic alcoholism. According to the Revised Atlanta Classification of Pancreatitis, 8 (18.0%) were diagnosed with moderate/severe and 395 (81.9%) with mild AP. When the data of these two groups were compared, the mean age of the patients, the length of hospital stay, the number of patients treated in the intensive care unit, the rate of comorbid hypertension, glucose values, percentages of immature granulocytes (% IG), procalcitonin (PC), CRP and leukocyte levels were significantly higher in the moderate/severe AP patient group.
Conclusion
AP predicts prognosis and severity; % IG ratio, leukocytes, CRP and PC values are important and effective biomarkers. Comorbidities and age are effective factors in the development of moderate/severe AP. By looking at these parameters, we can reduce mortality and morbidity by acting faster with the progress of AP.

Keywords

Introduction

Despite modern diagnostic and therapeutic procedures, acute pancreatitis remains a disease with a high morbidity and mortality risk.¹
It can progress in different severity, ranging from the mild clinical form such as edematous pancreatitis to severe clinical forms such as pancreatic necrosis and systemic organ damage. Therefore, the severity and course of the disease may vary. Although various classification/scoring criteria are used to determine the prognosis in patients with acute pancreatitis (AP), we cannot adequately detect severe pancreatitis cases at the time of diagnosis. Despite numerous biomarker, prognostic classification and imaging studies, it is difficult to predict severe cases.² Especially, in organ failures that develop as a result of pancreatic necrosis and systemic complications, mortality decreases with early diagnosis and early and effective initiation of treatment. SIRS (systemic inflammatory response syndrome) and organ failure in the first 2 weeks and sepsis and other complications after the 2nd week are the biggest causes of mortality.
The specificity and sensitivities of amylase and lipase values are very effective in diagnosing. However, they are not decisive for the severity of the disease and the prediction of complications. C-Reactive protein (CRP) and procalcitonin (PC) levels are used to confirm the diagnosis and predict prognosis. Studies show that immature granulocytes can be used as an early inflammation marker in the presence of inflammation. Studies examining the relationship between acute pancreatitis and immature granulocyte percentage (IG%) are limited. In these studies, the relationship between disease severity and IG% was examined.
The percentage of immature granulocytes is a new marker of inflammation that is not sufficiently known by most clinicians.³
CRP is an acute phase reactant secreted in the liver against Interleukin (IL) 1 and IL-6. CRP >150 mg/L in the first 48 hours distinguishes severe AP from mild. It is the most useful biochemical marker used to determine the severity and complications of AP.⁴
White blood cells (WBC) play an important role in the inflammatory process. In AP, the activation of leukocytes with inflammatory reactions and the cytokine storm that initiates the inflammatory process are responsible for the initiation of the systemic inflammatory response syndrome (SIRS), which is responsible for systemic complications, as well as local necrosis formation in the pancreas.⁵
Sepsis is an inflammatory process and one of the most important diagnostic and prognostic biomarkers is procalcitonin. It is an important indicator to determine the prognosis and severity of AP early and to diagnose infected pancreatic damage.⁶
Studies have shown that procalcitonin is an important prognostic factor in sepsis and acute pancreatitis.⁷
Any delay in diagnosis and treatment leads to an increase in morbidity and mortality rates. There is a need for a rapid, simple and reliable biomarker for the early recognition of AP and the prediction of its severity. Although various inflammation markers and complex scoring systems have been developed for this purpose, there is no ideal method yet.
The diagnostic value of ERCP in acute pancreatitis has been reported as 38 - 79% in the literature. Whether there is an accompanying acute cholangitis picture in acute biliary pancreatitis (ABP) is important in the decision-making process for ERCP.⁸ ERCP is indicated in the presence of cholangitis with acute calculous pancreatitis and in the presence of common bile duct obstruction with acute calculous pancreatitis. Routine ERCP is not recommended only with the prediction of severe AP without cholangitis or common bile duct obstruction.⁹
There is a need for highly sensitive biochemical biomarkers that can evaluate the severity and prognosis of this disease, which can cause organ failure and mortality, more quickly, simply and specifically.¹⁰

Materials and Methods

Between January 2020 and July 2022, S.B. 482 FP cases followed in Mehmet Akif Inan Training and Research Hospital were evaluated retrospectively.
Ethical Approval
Ethical approval for our study was obtained from Harran University Clinical Research Ethics Committee (decision dated 05.07.2021 and numbered HRU/21.13.07). Age, gender, comorbidity, clinical, laboratory and imaging examinations, length of hospital stay and clinical course of the patients were recorded.
Early recognition of severe pancreatitis and prognosis, which causes local or systemic complications in the clinical course of AP patients, and application of the necessary treatment are the most important factors affecting morbidity and mortality. In this study, we evaluated the routinely used biochemical markers, which are indicators of inflammation and infection, which can detect the prognosis and the severity of the disease early in patients hospitalized for AP.
The revised Atlanta Criteria were used to determine AP severity.
The effectiveness of PC, % IG, CRP and leukocyte levels, which are routinely checked in blood samples of patients hospitalized with the diagnosis of AP, in early detection of sepsis development were investigated.
Data were obtained retrospectively from patient files and hospital information systems.
Patients under the age of 18 and pregnant, patients receiving chemotherapy, patients hospitalized for less than two days, and patients whose data could not be reached were excluded from the study.

Results

When the data of our patients are examined, according to the Revised Atlanta Classification, 8 (18.0%) were diagnosed with moderate/severe and 395 (81.9%) with mild AP (Table 1).¹¹ Of the 482 patients admitted with the diagnosis of acute pancreatitis and followed up and treated, 267 (55.3%) were female and 215 (44.6%) were male. The mean age was 57.9 ± 21.05 years in women and 58.06 ± 17.34 years in men.
The mean age in the moderate and severe patient groups was 71.16 ± 14.16 years.
The mean age of patients with the mild course was 57.88 ± 20.90 years. The mean age of patients with the moderate and severe course was statistically significantly higher (p<0.0001).
There was no significant difference between the two patient groups in terms of gender (p=0.12).
Twenty-three (6.0%) of the mild patients and 77 (74.7%) of the moderate and severe patients were followed up in the intensive care unit. The mean hospital stay was 6 days in the mild cases group and 19 days in the moderate and severe patients group. When mild AP patients and moderate/severe AP patients were compared in terms of the number of patients receiving intensive care treatment and length of stay in the hospital, the number of patients in the moderate/severe AP group was significantly higher (p<0.0001).
Of the patients, 471 (98.1%) were biliary pancreatitis, 9 (1.8%) were hyperlipidemia and non-biliary due to chronic alcoholism, 2 (0.4%) were post-ERCP pancreatitis.
Of the 482 patients with acute pancreatitis, 27 (5.6%) resulted in mortality. Of the 27 patients, 1 (3.7%) had a mild course and 26 (96.2%) had a moderate/severe course.
Demographic data, etiological characteristics, length of hospital stay and intensive care unit admission rates are presented in Table 2.
In this study, the revised Atlanta Classification was used for the staging of severity in acute pancreatitis. The mean age of the patients was 73.36 ± 15.17 years in moderate and severe AP patients and 56.78 ± 19.80 in mild pancreatitis patients.
Moderate and severe pancreatitis developed in 103 (21.4%) of the patients hospitalized with the diagnosis of AP, and mild pancreatitis developed in 379 (78.6%). The mean age of the patients with moderate and severe severity was higher than the patients with the mild course (p<0.001).
When the two groups were compared, the length of hospital stay and the number of patients treated in the intensive care unit were higher in moderate and severe patients (p=0.0001) (p=0.0001).
The rate of previously diagnosed hypertension was higher in patients with moderate and severe courses compared to patients with the mild course.
High glucose levels were higher in moderate and severe patients than in mild patients.
The values in the blood samples taken at the admission of the patients are shown in Table 3.

Discussion

Acute pancreatitis can clinically progress from mild edematous to severe local pancreatic necrosis. Spontaneous recovery may occur, but in severe cases, metabolic disorders, sepsis, and organ failure, which can lead to death, can be observed clinically.¹
The specificity and sensitivities of amylase and lipase values are not high enough to make the diagnosis on their own and change hourly. In addition, leukocytes, CRP, IG% and procalcitonin levels are used to confirm the diagnosis and predict prognosis.
In patients with AP, different scoring systems such as Atlanta criteria, Ranson criteria, BISOP scoring, MARSHALL scoring and APACHE II criteria can be used to determine clinical course and prognosis. However, they are still not sufficient to predict severe pancreatitis cases. Despite many biomarkers, prognostic classifications, and imaging studies, it is difficult to predict severe cases early. It is possible to detect the formation of severe local pancreatic damage in patients after 48 hours. Therefore, many studies still need markers that can predict prognosis at the time of diagnosis.^12,13
In this study, the revised Atlanta Classification was used for staging the severity of acute pancreatitis. Thanks to this classification, detection of persistent organ failure (>48 h) with infected necrosis was determined as the most mortal picture, and follow-up of these patients in the intensive care unit was recommended.
In AP, the inflammatory reaction stimulates the cytokine system, resulting in SIRS. With persistent and continuous SIRS, dysfunctions occur in vital organs. While it may resolve within 48 hours in moderately severe AP, which can be seen as pancreatic necrosis, lung damage, shock and organ failure such as kidney failure, it may take longer than 48 hours in patients with severe acute pancreatitis.
In this study, we tried to be a guide for clinics following similar cases by trying to prove the effectiveness of biochemical and hematological markers in order to diagnose the severity and prognosis of AP early in light of the data we obtained from our large patient series.
In this study, according to the revised Atlanta classification, 21.4% of AP patients were moderate/severe and 78.6% were mild.
2 - 10% of mortality in AP occurs as a result of complications.¹⁴
It also increases the risk of severe AP complications and therefore mortality.¹⁵
The fastest diagnosis of AP can be achieved by clinical findings and biomarkers. Inflammatory or infection biomarkers such as CRP, PC, IG% and leukocytes are used in the diagnosis and more importantly in monitoring the prognosis and disease severity.¹⁶ Age, comorbidities and severity of acute pancreatitis are among the factors that affect the clinical course of the patient.
Cardiovascular complications are also observed in the course of acute pancreatitis. In this respect, the most common complications are heart failure and hypotension. Activated kinins in acute pancreatitis cause vasodilation and increased permeability. In addition, displacement of intravascular volume into the abdomen, activation of the renin-angiotensin system, and cytokines released due to inflamed pancreas may cause toxic effects on the myocardium, leading to the development of heart failure and hypotension.
In our study, the mean age was found to be 71.16 ± 14.16 in the patients with moderate and severe courses, and 57.88 ± 21.19 in the patients with the mild course. We found that advanced age is an effective factor in the severity of pancreatitis and poor prognosis. Gender had no effect on AP severity and prognosis.
Twenty-three (6.0%) of the mild patients and 77 (74.7%) of the moderate and severe patients were followed up in the intensive care unit. The mean hospital stay was 6 days in the mild cases group and 19 days in the moderate and severe patients group. Local and systemic complication rates increase due to the increase in the severity of AP and the worsening of its prognosis. As a result, the length of stay of the patients and the number of intensive care hospitalizations increase. Therefore, mortality due to AP also increases.
There was no difference between mild and moderate/severe patients in terms of AP etiology. Etiology was not found to be a determinant in the severity of AP.
IG% rates, PC, CRP and leukocyte values in the blood samples taken at the admission of the patients were statistically significantly higher in patients with moderate and severe courses compared to patients with the mild course.
High IG%, PC, CRP and leukocyte levels in patients with acute pancreatitis are indicative of poor prognosis and severe AP. Early initiation of aggressive and intensive care treatment with the prediction of severe AP is important in reducing morbidity and mortality.
Local and systemic serious complications may occur in the course of AP, which is an inflammatory disease. Local and systemic complications that increase morbidity and mortality are generally seen in moderate and severe pancreatitis. In terms of preventing permanent organ damage and/or mortality, the data we obtained in this study showed that biomarkers are important and effective in terms of early diagnosis of severe cases, prevention of complications and initiation of early treatment.

Conclusion

AP predicts prognosis and severity; %IG ratio, leukocytes, CRP and PC values are important and effective biomarkers. Comorbidities and age are effective factors in the development of moderate/severe AP. We can predict the prognosis of AP by looking at these values.

Declarations

References

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About This Article

Received:

December 3, 2022

Accepted:

January 13, 2023

Published Online:

January 31, 2023

Printed:

February 1, 2023