# Cell-Free DNA Hypermethylation in Patients with Acute Pancreatitis

## TL;DR

The study found that patients with acute pancreatitis have higher cell-free DNA hypermethylation at diagnosis, which decreases over time and correlates with disease severity markers.

## Contribution

This study is the first to longitudinally analyze cfDNA hypermethylation in acute pancreatitis and link it to clinical severity markers.

## Key findings

- AP patients had significantly higher hypermethylation at diagnosis compared to healthy controls.
- Hypermethylation levels decreased over time and normalized after 7–8 years.
- Total hypermethylation was positively associated with CRP, leukocyte count, and hospital stay.

## Abstract

Cell-free DNA (cfDNA) promoter hypermethylation shows promise as a blood-based biomarker for pancreatic cancer, and similar alterations may occur in acute pancreatitis (AP). This study investigated the cfDNA hypermethylation profile of AP patients over time, compared with healthy controls, and its association with AP severity markers. A prospective longitudinal study including hospitalized AP patients and healthy controls was conducted. Methylation-specific PCR of a 23-gene panel was performed on plasma collected at inclusion (T0), 6 weeks (T6W), 6 months (T6M), and 7–8 years (T8Y). Associations between gene hypermethylation and clinical markers of AP severity—CRP, leukocyte count, creatinine, hospital stay, and complications—were evaluated. AP patients had a significantly higher mean number of hypermethylated genes at T0 (7.4, 95% CI: 6.8–8.0) compared with the controls (3.3, 95% CI: 2.8–3.8; p < 0.01). The mean number decreased over time to 3.2 (95% CI: 2.4–4.1) at T8Y. Total hypermethylation was positively associated with CRP (ρ = 0.39; p = 0.0018), leukocytes (ρ = 0.35; p = 0.0052), and hospital stay (ρ = 0.27; p = 0.0375). AP patients exhibited significantly higher cfDNA hypermethylation at disease onset, which normalized over time. Total hypermethylation showed positive associations with several markers of AP severity.