Mechanisms and therapeutic advances in hyperlipidemic acute pancreatitis

Hyperlipidemic acute pancreatitis (HLAP) is an increasingly recognized form of acute pancreatitis driven by severe triglyceride-rich lipoprotein excess and characterized by complex metabolic, inflammatory, microcirculatory, and genetic interactions. This review aims to integrate current mechanistic evidence with recent clinical data and to distinguish established management principles from investigational approaches. Current evidence supports standard acute-pancreatitis supportive care, correction of metabolic precipitants, selective use of insulin when clinically appropriate, and early oral or enteral nutrition as tolerated. Rapid triglyceride reduction is a useful biochemical target, but it should not be assumed to improve organ failure or mortality; routine low-molecular-weight heparin for triglyceride lowering and universal early therapeutic plasma exchange are not supported by current comparative evidence. Fibrates, prescription omega-3 fatty acids, dietary fat restriction, weight control, glycemic optimization, and alcohol avoidance are primarily strategies for long-term triglyceride control and recurrence prevention rather than acute rescue therapies. Traditional Chinese medicine remains an adjunctive, investigational approach because of heterogeneity, limited external validation, and potential herb-drug interactions. APOC3 inhibition supports long-term prevention in selected chylomicronemia populations, and olezarsen now also has a US indication for reducing pancreatitis risk in severe hypertriglyceridemia; these preventive uses do not establish efficacy during an ongoing acute attack. Overall, treatment should prioritize patient-centered outcomes and individualized risk assessment rather than triglyceride reduction alone.