Complex interplay between hypertriglyceridemia and acute pancreatitis: a narrative review

In recent years, lifestyle and dietary transitions have driven a marked rise in hypertriglyceridemia as a cause of acute pancreatitis, particularly in Asian countries, including China, where hypertriglyceridemia now ranks as the second most common etiology. The relationship between triglycerides and acute pancreatitis is both complex and bidirectional, in that hypertriglyceridemia can precipitate acute pancreatitis and is linked to complications, greater disease severity, and poorer outcomes, while the onset of pancreatitis may itself elevate triglyceride levels further. This reciprocal interaction poses major challenges for diagnosis and prognostic evaluation when assessments rely solely on serum triglyceride concentrations. At present, there are no internationally consistent criteria for the diagnosis or prognostic assessment of hypertriglyceridemic acute pancreatitis. Therefore, elucidating the causal pathways and underlying mechanisms connecting triglycerides and pancreatitis is essential for improving diagnostic accuracy, refining risk stratification, and guiding the identification of therapeutic targets. This review synthesizes recent advances with a particular focus on causality and pathophysiological mechanisms, including cytotoxic effects of free fatty acids, microcirculatory disturbance, calcium overload, inflammatory response, oxidative stress, and genetic factors. It also highlights critical considerations regarding the development of standardized international diagnostic criteria. These include recognition of hypertriglyceridemia as an independent etiology, integration of the dynamics of free fatty acids into diagnostic algorithms, and clarification of the pathophysiological role of mild-to-moderate triglyceride elevations. By addressing these gaps, we aim to provide a foundation for consensus-building that will support more precise diagnosis and effective clinical management of this increasingly prevalent condition.