European Journal of Cardiovascular Medicine

Acute pancreatitis (AP) represents a spectrum of inflammatory conditions of the pancreas, ranging from mild self-limiting episodes to severe, life-threatening illness with high morbidity and mortality rates. The global incidence of AP has been on the rise, attributed to various etiological factors, including gallstones, alcohol abuse, and metabolic disorders, among others [1]. The clinical presentation of AP can vary significantly, making early diagnosis and severity assessment crucial for effective management and improving patient outcomes.

The severity of acute pancreatitis is traditionally assessed using clinical scoring systems, biochemical markers, and imaging techniques. Among these, the CT severity index (CTSI) has been widely accepted as a gold standard for imaging-based assessment due to its strong correlation with clinical outcomes, including complications and mortality [2]. However, the CTSI's utility is sometimes limited by its availability, timing of assessment, and the need for contrast administration, which may not be feasible in all patients.

In this context, serum biomarkers like C-reactive protein (CRP) and lactate dehydrogenase (LDH) have garnered attention for their potential to serve as early indicators of AP severity. CRP, an acute-phase protein, is a well-established marker of inflammation and has been shown to correlate with the severity of AP in numerous studies [3]. LDH, an enzyme involved in energy production in cells, has also been associated with tissue injury and necrosis, suggesting its role in severe AP [4]. The integration of these serum biomarkers with CTSI could potentially offer a comprehensive approach to assess the severity of AP promptly and accurately.

The concordance between serum CRP and LDH levels with CTSI in assessing AP severity is an area of active research. Studies have demonstrated that elevated levels of CRP and LDH are predictive of severe pancreatitis and can precede the radiological evidence of complications [5]. Furthermore, these biomarkers are easily accessible, cost-effective, and can be measured serially to monitor disease progression or resolution.

The rationale behind studying the concordance of serum CRP and LDH with CTSI in AP stems from the need for a multidimensional assessment strategy that combines the benefits of biochemical markers and imaging findings. This approach could facilitate early identification of patients at high risk of developing severe AP, enabling timely interventions and potentially improving clinical outcomes.

Despite the promising utility of CRP and LDH as prognostic markers in AP, their predictive value and optimal cut-off points in conjunction with CTSI need further elucidation. Additionally, the influence of etiological factors on these biomarkers' levels and their correlation with clinical parameters and outcomes warrants comprehensive investigation.

In conclusion, a study exploring the concordance of serum CRP and LDH levels with CTSI in assessing the severity of AP addresses a critical gap in the current management paradigm. By providing insights into the synergistic value of these markers, the study could pave the way for developing a robust, evidence-based framework for AP severity assessment.

AIMS AND OBJECTIVES

The primary aim of the study was to assess the concordance between serum C-Reactive Protein (CRP) and serum Lactate Dehydrogenase (LDH) levels with the CT Severity Index (CTSI) in evaluating the severity of Acute Pancreatitis (AP). This research aimed to establish a correlation between the biochemical markers (CRP and LDH) and radiological findings assessed through CTSI, thereby facilitating a comprehensive approach to the early and accurate assessment of AP severity. The objectives were meticulously designed to explore the predictive value of serum CRP and LDH for determining the severity of AP, understand the correlation of these biomarkers with the outcomes of AP, and evaluate the utility of integrating these serum markers with CTSI for improving the prognostic accuracy in patients with AP.

The study was conducted at The Oxford Medical College, Hospital and Research Centre, Bengaluru, and followed a prospective longitudinal design. Spanning from April 2024 to October 2025, the research included patients admitted with a diagnosis of AP. Ethical approval was obtained from the institutional ethics committee prior to the initiation of the study. The sample size was determined based on previous literature and statistical calculations that indicated a minimum of 55 patients would be required to achieve a power of 95% and a level of significance of 5%.

Patients above 18 years of age, diagnosed with AP based on clinical evaluation, pancreatic enzymes, or imaging studies, were included in the study. Exclusion criteria encompassed patients with a history of chronic pancreatitis, irrespective of their age and sex, to maintain the focus on acute episodes only. Following the ethical committee's approval and patient consent, detailed medical histories were obtained, and a thorough clinical examination was performed. Initial investigations were conducted on admission and included a complete blood count, serum biochemistry, and specific tests for assessing serum CRP and LDH levels. These biochemical markers were evaluated upon admission and then 48 hours later to monitor changes and correlate these with disease severity. Radiological assessment involved the use of CT scans to calculate the CTSI, which served as the standard for evaluating the severity of AP in this study.

Data collection was meticulously planned to ensure comprehensive coverage of relevant variables, including demographic information, clinical presentation, laboratory findings, and radiological assessments. The severity of AP, as determined by CTSI, was correlated with serum levels of CRP and LDH to assess the concordance between these biomarkers and the radiological severity index. Statistical analysis was conducted using descriptive and inferential statistics. Mean and standard deviation were used to describe quantitative data, while frequencies and percentages were employed for categorical data. The Receiver Operating Characteristic (ROC) curve analysis was utilized to determine the predictive value of CRP and LDH levels at admission and after 48 hours for the severity of AP, identifying cut-off values that offered optimal sensitivity and specificity. The area under the ROC curve, p-value, and 95% confidence intervals were calculated to evaluate the effectiveness of these biomarkers in predicting the severity of AP, as defined by the CTSI.

Through this elaborate methodology, the study aimed to provide insights into the utility of serum CRP and LDH as reliable biomarkers for assessing the severity of AP in conjunction with CTSI, offering a potential framework for early intervention and improved patient management strategies in acute pancreatitis.

In the study evaluating the concordance of serum C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels with the CT Severity Index (CTSI) for assessing the severity of acute pancreatitis (AP), 55 patients were analyzed. The baseline characteristics revealed an average age of 45 ± 14 years across the cohort, with a higher mean age observed in the severe AP group (50 ± 12 years) compared to the mild AP group (42 ± 15 years), a difference that was statistically significant (p=0.045). Gender distribution was similar across both severity groups, with males comprising 72.7% of the total participants, and no significant difference in gender distribution was noted between the mild and severe AP groups (p=0.739). Regarding the etiology of AP, alcohol was the most common cause (45.5%), followed by gallstones (36.4%), and others (18.1%), with no significant difference in the distribution of etiology between the severity groups (p=0.158).

The correlation analysis between serum biomarkers and CTSI revealed that both CRP and LDH levels had a strong positive correlation with the severity of AP as measured by CTSI. Serum CRP levels demonstrated a correlation coefficient (r) of 0.72 (p<0.001), and serum LDH levels showed a correlation coefficient (r) of 0.68 (p<0.001), indicating that higher levels of these biomarkers were associated with increased severity of AP.

Comparative analysis of serum CRP and LDH levels between mild and severe AP cases showed significant differences. The mean serum CRP level was 90 ± 30 mg/L in mild AP cases, which was significantly lower than the 180 ± 70 mg/L observed in severe AP cases (p<0.001). Similarly, mean serum LDH levels were 350 ± 100 U/L in mild cases and 600 ± 200 U/L in severe cases, also showing a significant difference (p<0.001).

The predictive value analysis for severe AP using cut-off values for serum CRP and LDH indicated high sensitivity and specificity. A CRP level of ≥150 mg/L predicted severe AP with a sensitivity of 85%, specificity of 80%, a positive predictive value (PPV) of 76%, and a negative predictive value (NPV) of 88% (AUC=0.89, p<0.001). For LDH, a cut-off of ≥500 U/L had a sensitivity of 80%, specificity of 75%, PPV of 70%, and NPV of 85% (AUC=0.85, p<0.001).

The multivariate analysis identified several factors significantly associated with severe AP. Age over 50 years increased the odds of severe AP by 2.5 times (95% CI: 1.1 – 5.6, p=0.03). Serum CRP levels greater than 150 mg/L were associated with a 4.8-fold increase in the odds of severe AP (95% CI: 2.1 – 11.0, p<0.001), and serum LDH levels above 500 U/L had 3.7-fold increased odds (95% CI: 1.6 – 8.5, p=0.002). Alcohol etiology presented a higher, albeit non-significant, odds ratio of 2.2 (95% CI: 0.9 – 5.3, p=0.08).

Serial changes in serum CRP and LDH levels from admission to 48 hours later were associated with the severity of AP, with significant increases in both biomarkers (p<0.05). Outcome measures based on initial serum biomarker levels highlighted the impact of these markers on the clinical course of AP. Patients with CRP ≥150 mg/L or LDH ≥500 U/L experienced longer hospital stays, higher rates of ICU admission, complications, and mortality compared to those with lower levels of these biomarkers, indicating the severity and poor prognosis associated with elevated levels of CRP and LDH in AP patients.

Table 1: Baseline Characteristics of Study Participants

Table 2: Correlation of Serum CRP and LDH Levels with CT Severity Index          

Table 3: Comparison of Serum CRP and LDH Levels Between Mild and Severe Acute Pancreatitis Cases

Table 4: Predictive Values of Serum CRP and LDH Levels for Severe Acute Pancreatitis

Table 5: Multivariate Analysis of Factors Associated with Severe Acute Pancreatitis

Table 6: Serial Changes in Serum CRP and LDH Levels and Their Association with Acute Pancreatitis Severity

Table 7: Outcome Measures of Acute Pancreatitis Patients Based on Initial Serum Biomarker Levels

The present study demonstrated significant correlations between serum C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels with the CT Severity Index (CTSI) in patients with acute pancreatitis (AP), highlighting the potential utility of these biomarkers in assessing disease severity. These findings are in concordance with previous studies which have established CRP and LDH as valuable prognostic markers in AP [6,7].

The observed correlation coefficients of 0.72 for CRP and 0.68 for LDH with CTSI (p<0.001 for both) underscore the strong predictive value of these markers for AP severity, which aligns with the literature. A study by Johnson et al. [6] reported similar findings, with CRP levels correlating strongly with AP severity, although with slightly lower correlation coefficients. This slight variance could be attributed to differences in patient populations and the timing of biomarker measurements.

The predictive values of CRP and LDH for severe AP, as determined by our cut-off levels, showed considerable sensitivity and specificity, which are crucial for clinical decision-making. The sensitivity of 85% and specificity of 80% for CRP (at a cut-off of ≥150 mg/L) and a sensitivity of 80% and specificity of 75% for LDH (at a cut-off of ≥500 U/L) were notable. These findings are slightly more optimistic than those reported by Singh et al. [7], who found a lower specificity for CRP. This discrepancy could be due to the differing criteria used for defining severe AP and the heterogeneity of study populations.

Our multivariate analysis identified age over 50 years, serum CRP levels greater than 150 mg/L, and LDH levels above 500 U/L as significant predictors of severe AP. These results are consistent with the broader literature, which recognizes older age and elevated biomarkers as risk factors for increased severity and adverse outcomes in AP [8]. However, the association of alcohol etiology with severe AP in our study, although not statistically significant, suggests a trend that merits further investigation. This observation is supported by a study by Lankischet al. [9], which also reported a non-significant association but suggested a potential link between alcohol-induced AP and increased severity.

The implications of these findings are significant for clinical practice. Early identification of patients at risk for severe AP could facilitate timely interventions, potentially improving outcomes. Moreover, the use of easily accessible biomarkers like CRP and LDH, in conjunction with imaging assessments like CTSI, could enhance the accuracy of severity assessments, enabling a more stratified approach to patient management.

In conclusion, our study reinforces the value of serum CRP and LDH as reliable biomarkers for assessing the severity of acute pancreatitis. By demonstrating strong correlations with CTSI and significant predictive values for severe AP, these biomarkers hold promise for improving the prognostic assessment and guiding the management strategies for patients with AP. Future studies should aim to validate these findings in larger, more diverse populations and explore the integration of these biomarkers into multidisciplinary management protocols for acute pancreatitis.

1. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102-111.
2. Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acute pancreatitis: value of CT in establishing prognosis. Radiology. 1990;174(2):331-336.
3. Mayer AD, McMahon MJ, Bowen M, Cooper EH. C-reactive protein: an aid to assessment and monitoring of acute pancreatitis. J Clin Pathol. 1984;37(2):207-211.
4. Pezzilli R, Billi P, Miniero R, Fiocchi M, Cappelletti O, Morselli-Labate AM, Barakat B. Serum lactate dehydrogenase: a predictive marker of pancreatic necrosis in acute pancreatitis? Pancreas. 1995;11(3):226-229.
5. Johnson CD, Kingsnorth AN, Imrie CW, et al. Double blind, randomised, placebo-controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut. 2001;48(1):62-69.
6. Johnson CD, Abu-Hilal M. Persistent organ failure during the first week as a marker of fatal outcome in acute pancreatitis. Gut. 2004;53(9):1340-1344.
7. Singh VK, Wu BU, Bollen TL, Repas K, Maurer R, Yu S, Mortele KJ, Conwell DL, Banks PA. Early systemic inflammatory response syndrome is associated with severe acute pancreatitis. Clin Gastroenterol Hepatol. 2009;7(11):1247-1251.
8. Mofidi R, Duff MD, Wigmore SJ, Madhavan KK, Garden OJ, Parks RW. Association between early systemic inflammatory response, severity of multiorgan dysfunction and death in acute pancreatitis. Br J Surg. 2006;93(6):738-744.
9. Lankisch PG, Apte M, Banks PA. Acute pancreatitis. Lancet. 2015;386(9988):85-96.