Introduction

96-98% of patients survive acute pancreatitis (AP), but in the post-AP phase, patients are at high risk of morbidity and mortality. It has been shown that pancreatic exocrine insufficiency can occur after AP.

Aims & Methods

We aimed to investigate the rate, risk factors, and the effect of pancreatic enzyme replacement therapy (PERT) for PEI in patients with AP. The study protocol was registered on PROSPERO (CRD42024516403). We conducted a systematic search on 5 February 2024 in three databases (PubMed, EMBASE, and CENTRAL). We included in the analysis studies reporting on risk factors and PERT efficacy in PEI associated with AP. Pooled proportion and odds ratios (OR) with a 95% confidence interval (CI) were calculated using a random effect model.

Results

Fifty-six articles were included in our meta-analysis. Among 17896 patients with AP, the pooled proportion of PEI was 20 % ([CI]: 15–26). The odds of PEI development were two-fold higher in severe acute pancreatitis (OR=2.44, [CI]: 0.98–6.11) compared with mild or moderate AP and three times higher after necrosectomy compared to patients without necrosectomy (OR=3.26, [CI]: 1.6–6.64). There was no significant difference between the odds of PEI among AP patients with necrosis (OR=1.43, [CI]: 0.32–6.45) and those without necrosis. However, the odds of PEI were twice as high in patients with infected necrosis (OR=2.13, [CI]: 0.93–4.87) than in patients with sterile necrosis. Pancreatic enzyme replacement therapy was prescribed for 22% ([CI]: 16–30) of patients after AP.

Conclusion

One in five patients with AP develops PEI. The rate is higher in patients with severe AP, infected necrosis, or who need necrosectomy. Patients with AP should be screened for PEI to allow timely PERT administration.

Introduction

Chronic pancreatitis is a progressive inflammatory disease characterized by irreversible damage to the pancreas. The etiology of the disease is heterogenous and includes alcohol abuse, smoking, genetic risk factors and autoimmune diseases. Several clinical classification and severity scoring systems have been proposed, but none have been globally accepted or reached broad clinical use. Identifying patients at a higher risk of death is crucial for improving patient care and management.

Aims & Methods

This study aimed to develop a prediction model based on promoter hypermethylation of specific genes and clinical factors to differentiate patients with chronic pancreatitis who are at a higher risk of mortality. Clinical variables such as age, sex, smoking status, alcohol consumption, exocrine insufficiency, and endocrine insufficiency, as well as the methylation status of 16 genes, were analyzed using a backward stepwise Cox regression model. The methylation status was determined by a specialized bisulfite based PCR technique. The final model's performance was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), and used to determine a risk score for each patients. The “cutpt” package in Stata was used to determine an optimal cut-off, in order to stratify patients into low and high-risk groups. Kaplan-Meier survival curves, and cox regression, and AUC were used to determine the accuracy of the risk groups.

Results

Ninety-seven patients with chronic pancreatitis were included in the study. The final prediction model included age, sex, exocrine insufficiency, endocrine insufficiency, and the methylation status of 5 genes: SFRP2, HIC1, MLH1, RASSF1A, and CDKN2B. The AUC of the model was 0.84, indicating high reliability. The model was superior to a model including only clinical variables (AUC = 0.76), indicating added value of the methylation markers. The optimal cut-off value for the risk score was 7.76. According to this, 67 patients were in the low-risk group, and 30 in the high-risk group. The 5-year survival in the high-risk group was 53% compared to 94% in the low-risk group. Being in the high-risk group was significantly associated with an increased HR of death of 10.2 (95% CI; 4.9-21.1), demonstrating the model's strong prognostic value.

Conclusion

The developed prediction model, which combines clinical factors and gene promoter hypermethylation status, could be a valuable tool for identifying patients with chronic pancreatitis who are at a higher risk of death. This study serves as proof-of-concept of the unexplored potential of methylation analysis in cell-free DNA in chronic pancreatitis. This model can potentially enhance patient care by enabling targeted interventions and monitoring for high-risk individuals, ultimately improving their prognosis and quality of life.

Disclosure

S.D.H., P.H.M., O.T.-U., and H.B.K. declare that they have a patent on a diagnostic panel including the promoter hypermethylation status of 8 genes. Application No. 16161073.8 – 1403 Pancreatic Cancer methylation Markers (18.03.2016)