Hypertriglyceridaemia-Associated Acute Pancreatitis: Pathophysiological Insights and Advances in Clinical Management

Hypertriglyceridaemia (HTG) is an increasingly recognised aetiology of acute pancreatitis (AP), driven by the global rise in metabolic disorders. Although traditionally defined by triglyceride levels ≥ 1000 mg/dL, emerging evidence suggests a continuum of risk in which both genetic predisposition and secondary metabolic stressors contribute to disease onset and severity. Mechanistically, HTG-AP is characterised by lipotoxic injury mediated by free fatty acids, microcirculatory dysfunction, and amplified inflammatory responses, resulting in increased risk of organ failure and recurrence compared with AP of other aetiologies. Recent guideline updates emphasise early risk stratification, goal-directed supportive care, and prompt identification of underlying causes; however, HTG-specific management strategies remain heterogeneous. While insulin therapy and extracorporeal lipid removal techniques (e.g., plasmapheresis) are widely used, high-quality evidence supporting their superiority is limited. Long-term prevention relies on aggressive lipid control and modification of metabolic risk factors. This review provides a comprehensive synthesis of the aetiology, pathophysiology, clinical characteristics, and management of HTG-AP, highlighting recent advances, ongoing controversies, and future directions towards precision medicine.