Discussion

The present study demonstrates a substantial disease burden in ACP, characterized by a mortality rate of 12.1% and an ICU admission rate of 60.3% [3]. The most significant finding was the contrast in prognostic utility between the two time points. While admission PCT showed limited predictive value (AUC = 0.555), the 48-hour measurement demonstrated excellent accuracy (AUC = 0.992) for predicting mortality. Furthermore, serial PCT levels showed a very strong positive correlation with the duration of hospitalization (r > 0.95), confirming their utility as dynamic markers of severity. The superior performance of the 48-hour measurement reflects the kinetics of the inflammatory cascade. As the condition progresses, acinar cell damage triggers a systemic inflammatory response, during which multiple organs release PCT [10,17]. This process leads to cytokine amplification and delayed organ dysfunction, which becomes detectable within the 48-hour window [1,20]. Our findings mirror existing AP literature, in which Rau et al. [18] and Kylänpää-Bäck et al. [12] established PCT as a predictor of infected necrosis and organ failure, respectively.

In the unique context of ACP, it is hypothesized that pre-existing fibrosis may act as a protective barrier, potentially leading to a lower mortality risk compared to AP in a naïve pancreas [21,22]. This structural change also alters the biomarker profile; ACP patients often show lower-than-normal increases in pancreatic enzymes like amylase and lipase because chronic damage has caused significant tissue loss [6,23,24]. While enzymes lack prognostic utility, PCT reflects the true clinical complexity by matching the severity of SIRS activation and organ failure [17]. The clinical implications suggest that serial PCT monitoring should be integrated into triage protocols. In resource-limited settings, the 100% NPV at a threshold of 4.04 ng/mL provides a powerful tool for ruling out mortality risk and rationalizing ICU allocation [25]. Future research should validate these thresholds in larger multicentric cohorts to optimize risk stratification in this unique patient population.

The clinical implications of these findings are especially important in tertiary care and resource-limited healthcare settings, where early identification of high-risk patients is essential for appropriate allocation of intensive care resources and timely therapeutic intervention. Patients with persistently elevated or rising PCT levels demonstrated a significantly greater likelihood of developing organ dysfunction and local pancreatic complications, suggesting that serial PCT assessment may assist clinicians in identifying patients who require closer monitoring and aggressive supportive management. Conversely, lower 48-hour PCT levels demonstrated excellent negative predictive value, potentially allowing clinicians to identify lower-risk patients suitable for management in general wards or for earlier step-down care.

Compared with invasive diagnostic approaches such as fine-needle aspiration, serial PCT measurement provides a rapid, minimally invasive, and clinically practical alternative for prognostic assessment. Furthermore, the strong association between serial PCT dynamics and duration of hospital stay suggests that this biomarker may also assist healthcare systems in anticipating resource utilization and planning patient care more effectively. Incorporating serial PCT monitoring into routine clinical protocols may therefore improve individualized management strategies and optimize decision-making throughout the course of ACP.

The present study also demonstrated that PCT possesses several advantages over conventional inflammatory and pancreatic biomarkers in ACP. Although CRP is widely used to assess inflammatory severity, its slower kinetic response limits its utility during the critical early phase of disease progression. In contrast, the rapid rise of PCT allows earlier identification of patients at increased risk of severe complications. Traditional pancreatic enzymes such as amylase and lipase remain useful for establishing the diagnosis of pancreatitis; however, their prognostic utility is limited because serum levels often normalize regardless of disease severity.

In ACP specifically, chronic acinar destruction frequently leads to only modest enzyme elevation, thereby reducing their reliability as indicators of clinical progression. In the present cohort, admission amylase and lipase levels were elevated but did not independently predict adverse outcomes. PCT, on the other hand, appeared to more accurately reflect the magnitude of systemic inflammatory activation and organ dysfunction, thereby offering a broader assessment of disease trajectory than biomarkers confined primarily to pancreatic tissue injury. Furthermore, incidentally, the strong negative correlation found between vitamin D₃ levels and hospital stay (r = −0.832) suggested that nutritional status may further influence recovery [26]

Analysis of mortality patterns demonstrated that respiratory failure and systemic organ dysfunction were the predominant terminal events. ARDS accounted for nearly half of all deaths, highlighting the critical role of systemic inflammatory response and pulmonary complications in severe pancreatitis. The occurrence of MODS, septic shock, and infected pancreatic necrosis with sepsis further emphasizes that mortality in ACP is largely attributable to persistent organ failure and secondary infectious complications rather than localized pancreatic injury alone. These observations are consistent with existing literature indicating that organ failure remains the principal determinant of mortality in severe pancreatitis.

Several strengths of the study should be acknowledged. The prospective observational design enabled systematic collection of clinical, biochemical, and radiological data in a standardized manner. An additional methodological strength was the use of serial biomarker assessment rather than reliance on a single baseline value, allowing evaluation of dynamic inflammatory changes over time. Moreover, the study specifically focused on a relatively understudied but clinically important subgroup of patients with imaging-confirmed ACP, thereby providing disease-specific evidence that is frequently underrepresented in broader pancreatitis research.

However, certain limitations must also be considered. The study was conducted at a single tertiary care centre, which may limit generalizability to other healthcare settings and patient populations. The relatively small sample size also reduced statistical power, particularly for mortality-related subgroup analyses. In addition, the observational design precludes causal inference between elevated PCT levels and adverse clinical outcomes. The study did not directly compare PCT with established prognostic scoring systems such as APACHE II or BISAP, nor with emerging inflammatory biomarkers including interleukin-6. Furthermore, long-term follow-up beyond hospitalization was unavailable, preventing evaluation of recurrence rates, chronic disease progression, and long-term survival outcomes. Therefore, although the identified 48-hour PCT threshold demonstrated excellent predictive performance within this cohort, further validation in larger multicenter studies remains necessary before widespread clinical application can be recommended.

Future research should focus on validating serial PCT thresholds in larger multicentric cohorts involving diverse demographic and clinical populations. Combining serial PCT measurements with established severity scoring systems such as BISAP or Modified Marshall scores may improve predictive accuracy and facilitate development of more comprehensive prognostic models. Additional exploration of multimarker approaches incorporating inflammatory, metabolic, and nutritional parameters may further enhance risk stratification in ACP. Emerging applications of artificial intelligence and machine learning also offer promising opportunities for developing predictive algorithms capable of identifying high-risk patients early in the disease course. As ACP becomes increasingly recognized as a distinct clinicopathological entity, the development of a dedicated ACP-specific prognostic scoring system incorporating serial inflammatory kinetics and chronic pancreatic structural changes may substantially improve patient management and outcome prediction.

The present study demonstrates that serial serum PCT monitoring, particularly at 48 hours after admission, may serve as a highly effective prognostic tool in patients with ACP. While admission PCT values alone demonstrated limited predictive utility, serial assessment provided excellent discrimination for mortality and severe disease outcomes. These findings emphasize the importance of systemic inflammatory kinetics, rather than isolated pancreatic injury markers, in determining prognosis in ACP. Integration of serial PCT monitoring into structured management protocols may improve early risk stratification, optimize healthcare resource allocation, and support more individualized patient care in this complex inflammatory disorder.