Chronic and recurrent acute idiopathic pancreatitis remains a clinical challenge, particularly regarding the management of disease flares, interventional therapies and long-term outcomes. This study aimed to identify potential risk and protective factors associated with clinical outcomes and to guide therapeutic management, particularly endoscopic and surgical strategies, in these patients.

We conducted a retrospective single-centre cohort study at a tertiary university hospital, including 80 consecutive patients with chronic or recurrent acute idiopathic pancreatitis carrying at least one pathogenic or likely pathogenic variant associated with hereditary or genetic pancreatitis. The main outcome was clinical remission, defined as absence of symptoms and no stent dependency at last follow-up, in patients who underwent at least one interventional treatment. Demographic, genetic, morphological and clinical variables were collected. Univariable logistic regression was used to assess predictors of clinical remission. Cox proportional hazards models were applied to evaluate time-to-event outcomes, using death, documented recurrence or ongoing stent dependency as events.

Among 80 patients, 32.5% (n=26) were children (age at diagnosis <18 years) and 60% (n=48) were female. The median age at diagnosis was 27 years (IQR 13–46), and 9 years (IQR 7–13) among children. A total of 120 genetic variants were identified, including 39 CFTR, 36 PRSS1 and 28 SPINK1 mutations. A positive family history of pancreatitis was present in 28.8% (n=23). Pancreas divisium and toxic exposure were each present in 35% (n=28). Exocrine and endocrine insufficiency occurred in 33.8% (n=27) and 22.5% (n=18), respectively. One patient died from pancreatic cancer. Fifty-five patients underwent at least one interventional treatment, with a median of 2 procedures (IQR 0–5). A total of 323 interventions were performed, including 8 pancreatic resections and 7 drainage surgeries. The median disease duration at first interventional treatment was 4 years (IQR 0–9). The median total follow-up was 12.5 years (IQR 4.3–16.8), and the median follow-up after the last interventional treatment was 12 months (IQR 2–24). At the last clinical evaluation, 71% (n=39) of treated patients were asymptomatic and free of stenting, with a median post-interventional follow-up of 17 months (IQR 7–37) in this subgroup. In univariable logistic regression, none of the demographic, genetic or clinical variables reached statistical significance for predicting clinical remission. However, older age at diagnosis (OR 1.01; 95% CI 0.98–1.04; p=0.59) and longer disease duration at first interventional treatment (OR 1.04; 95% CI 0.96–1.13; p=0.36) trended toward higher odds of remission. Conversely, pancreas divisium (OR 0.34; 95% CI 0.10–1.12; p=0.076), toxic exposure (OR 0.39; 95% CI 0.11–1.33; p=0.13) and endocrine insufficiency (OR 0.43; 95% CI 0.12–1.54; p=0.20) trended toward lower odds of remission. In multivariable logistic regression including pancreas divisium, toxic exposure, endocrine insufficiency, disease duration at first treatment and age at diagnosis, none of the variables reached statistical significance (all p>0.10), although pancreas divisium (adjusted OR 0.44; 95% CI 0.13–1.50; p=0.19) and toxic exposure (adjusted OR 0.34; 95% CI 0.09–1.38; p=0.13) remained associated with lower odds of remission. In Cox proportional hazards analysis, pancreas divisium was associated with a higher hazard of clinical recurrence (HR 2.83; 95% CI 1.02–7.87; p=0.046), whereas no other clinical, genetic or morphological factor showed a robust association with time-to-event outcomes. Although the Cox model suggested a higher hazard of recurrence in patients with pancreas divisium (HR ≈ 2.8), the log-rank test comparing Kaplan–Meier curves did not reach statistical significance (p=0.23).

Despite the heterogeneity of disease expression, 71% of treated patients achieved clinical remission, indicating that most individuals derived meaningful benefit from interventional treatment management. Older age at diagnosis and longer disease duration at first interventional treatment tended to be associated with a higher likelihood of remission. Conversely, pancreas divisium, toxic exposure and endocrine insufficiency tended to be associated with a higher risk of recurrence, although these trends did not hold statistical significance.