Severe hypertriglyceridemia (sHTG), defined as a triglyceride (TG) concentration ≥ 500 mg/dL (≥ 5.7 mmol/L) is an important risk factor for acute pancreatitis. Although lifestyle, some medications, and certain conditions such as diabetes may lead to HTG, sHTG results from a combination of major and minor genetic defects in proteins that regulate TG lipolysis. Familial chylomicronemia syndrome (FCS) is a rare disorder caused by complete loss of function in lipoprotein lipase (LPL) or LPL activating proteins due to two homozygous recessive traits or compound heterozygous traits. Multifactorial chylomicronemia syndrome (MCS) and sHTG are due to the accumulation of rare heterozygous variants and polygenic defects that predispose individuals to sHTG phenotypes. Until recently, treatment of sHTG focused on lifestyle interventions, control of secondary factors, and nonselective pharmacotherapies that had modest TG-lowering efficacy and no corresponding reductions in atherosclerotic cardiovascular disease events. Genetic discoveries have allowed for the development of novel pathway-specific therapeutics targeting LPL modulating proteins. New targets directed towards inhibition of apolipoprotein C-III (apoC-III), angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like protein 4 (ANGPTL4), and fibroblast growth factor-21 (FGF21) offer far more efficacy in treating the various phenotypes of sHTG and opportunities to reduce the risk of acute pancreatitis and atherosclerotic cardiovascular disease events.

严重高甘油三酯血症（sHTG），定义为甘油三酯（TG）浓度≥500mg/dL（≥5.7mmol/L），是急性胰腺炎的重要危险因素。虽然生活方式、某些药物和某些疾病（例如糖尿病）可能会导致 HTG，但 sHTG 是由调节 TG 脂解作用的蛋白质中的主要和次要遗传缺陷共同导致的。家族性乳糜微粒血症综合征 (FCS) 是一种罕见疾病，由两种纯合隐性性状或复合杂合性状导致脂蛋白脂肪酶 (LPL) 或 LPL 激活蛋白功能完全丧失而引起。多因素乳糜微粒血症综合征 (MCS) 和 sHTG 是由于罕见杂合变异和多基因缺陷的积累导致个体易出现 sHTG 表型。直到最近，sHTG 的治疗仍集中在生活方式干预、次要因素控制和非选择性药物疗法上，这些疗法具有适度的 TG 降低功效，但没有相应减少动脉粥样硬化性心血管疾病事件。基因发现使得针对 LPL 调节蛋白的新型途径特异性疗法的开发成为可能。针对载脂蛋白 C-III (apoC-III)、血管生成素样蛋白 3 (ANGPTL3)、血管生成素样蛋白 4 (ANGPTL4) 和成纤维细胞生长因子 21 (FGF21) 抑制的新靶点在治疗sHTG 的各种表型以及降低急性胰腺炎和动脉粥样硬化性心血管疾病事件风险的机会。