Impact of Acute Pancreatitis Aetiology on Long-Term Outcomes Following a First Episode of Acute Pancreatitis: A Systematic Review and Meta-Analysis.

Background: Acute pancreatitis (AP) is increasingly recognised as a disease with clinically significant long-term consequences. However, the extent to which aetiology influences the spectrum of long-term pancreatic sequelae remains unclear. This systematic review and meta-analysis evaluated long-term complications following a first episode of AP, with a protocol-defined focus on the impact of aetiology. Methods: This review evaluated eligible studies that included adults with a first episode of AP who were followed for chronic pancreatitis (CP), exocrine pancreatic insufficiency (EPI), or new-onset diabetes mellitus (NODM). A comprehensive search of PubMed, Scopus, Web of Science, and CENTRAL was conducted from January 2002 to June 2025. Risk of bias was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analyses were performed to estimate pooled incidence proportions. A prespecified network meta-analysis was not feasible because outcome-specific event counts stratified by aetiology were inconsistently reported. This study satisfied PRISMA 2020 guidelines and was registered with PROSPERO (CRD420251074032). Results: Eight studies met eligibility criteria with extractable data for quantitative synthesis. Five studies (n ≈ 10,780) reported chronic pancreatitis (CP), with a pooled incidence of approximately 7-8% following a first episode of acute pancreatitis (AP) and substantial heterogeneity (I2 ≈ 96%). Three studies (n = 796) reported exocrine pancreatic insufficiency (EPI), with a pooled incidence of approximately 23%, although estimates were highly heterogeneous (I2 ≈ 98%). Four studies (n = 2706; 415 events) reported new-onset diabetes mellitus (NODM), with a pooled incidence of approximately 20% (I2 ≈ 93%). Although aetiology-specific quantitative comparisons were not possible, narrative synthesis consistently demonstrated higher long-term risk following alcohol-associated AP, lower risk after biliary AP, and intermediate but variable outcomes in idiopathic AP. Conclusions: Clinically meaningful long-term pancreatic dysfunction is common after a first episode of acute pancreatitis, particularly new-onset diabetes mellitus. While aetiology-specific risks could not be quantified, consistent patterns suggest that aetiology shapes long-term outcomes. These findings support structured, aetiology-informed follow-up after acute pancreatitis and the need for standardised outcome reporting in future studies.